RESOURCES

COVID-19 Scientific Resources

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This online resource page is provided by the Geneva Centre for Education & Research in Humanitarian Action, the University of Geneva and the Graduate Institute of International and Development Studies (IHEID), and aims to inform governments, humanitarian organisations and media representatives on the latest evidence on the COVID-19 virus. This page, updated daily, includes systematic reviews and primary and secondary analysis and it also refers to online resources from reputable organisations where updated information is published.

If you need more detailed information, please contact our Director, Professor Karl Blanchet (karl.blanchet@unige.ch)

The Centre is also hosting a weekly webinar series on COVID-19 and humanitarian settings, in collaboration with the READY Initiative, the London School of Hygiene and Tropical Medicine (LSHTM) and the Centre for Humanitarian Health at Johns Hopkins University. To complement this initiative, COVID-19 Humanitarian, an open access, web-based platform, has been created to promote and value the collection and sharing of field-based COVID-19 programme adaptations and innovations, facilitating learning among organizations in different sectors and contexts.

Scientific evidence on covid-19 virus


 

This selection of scientific articles covers the time period between 16 March - 8 May.

 

8 May, 2020, 14.oo CET

 

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

Joshua Geleris et al.
7 May 2020, in NEJM
Background:  Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use.
Methods:  We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score.

Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing
Luca Ferretti et al.
8 May 2020, in Science
Introduction:  Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), has clear potential for a long-lasting global pandemic, high fatality rates, and incapacitated health systems. Until vaccines are widely available, the only available infection prevention approaches are case isolation, contact tracing and quarantine, physical distancing, decontamination, and hygiene measures. To implement the right measures at the right time, it is of crucial importance to understand the routes and timings of transmission.
Rationale:  We used key parameters of epidemic spread to estimate the contribution of different transmission routes with a renewal equation formulation, and analytically determined the speed and scale for effective identification and contact tracing required to stop the epidemic.

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV
Meng Yuan et al.
8 May 2020, in Science
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the “up” conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.

An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China
Huaiyu Tian et al.
8 May 2020, in Science
Responding to an outbreak of a novel coronavirus [agent of coronavirus disease 2019 (COVID-19)] in December 2019, China banned travel to and from Wuhan city on 23 January 2020 and implemented a national emergency response. We investigated the spread and control of COVID-19 using a data set that included case reports, human movement, and public health interventions. The Wuhan shutdown was associated with the delayed arrival of COVID-19 in other cities by 2.91 days. Cities that implemented control measures preemptively reported fewer cases on average (13.0) in the first week of their outbreaks compared with cities that started control later (20.6). Suspending intracity public transport, closing entertainment venues, and banning public gatherings were associated with reductions in case incidence. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50).

Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019
Diangeng Li et al.
7 May 2020, in JAMA
In December 2019, an outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, and rapidly spread to other parts of China and overseas.1 It has been confirmed that COVID-19 has the characteristic of human-to-human transmission, mainly through respiratory droplets and contact. Other routes require further verification. The virus responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in stool, gastrointestinal tract, saliva, and urine samples. However, little is known about SARS-CoV-2 in semen.
Groups were compared using the t test,
χ2 test, or Mann-Whitney or Kruskal-Wallis test. All statistical analyses were performed using SPSS statistical software version 19 (IBM). P values were 2-tailed, and P < .05 was considered to indicate significant differences.

Estimated Demand for US Hospital Inpatient and Intensive Care Unit Beds for Patients With COVID-19 Based on Comparisons With Wuhan and Guangzhou, China
Ruoran Li et al.
6 May 2020, in JAMA
Importance : Sustained spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has happened in major US cities. Capacity needs in cities in China could inform the planning of local health care resources.
Objectives : To describe and compare the intensive care unit (ICU) and inpatient bed needs for patients with coronavirus disease 2019 (COVID-19) in 2 cities in China to estimate the peak ICU bed needs in US cities if an outbreak equivalent to that in Wuhan occurs.
Design, Setting, and Participants: This comparative effectiveness study analyzed the confirmed cases of COVID-19 in Wuhan and Guangzhou, China, from January 10 to February 29, 2020.
Exposures: Timing of disease control measures relative to timing of SARS-CoV-2 community spread.
Main Outcomes and Measures: Number of critical and severe patient–days and peak number of patients with critical and severe illness during the study period.

Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures
Kenrie P. Y. Hui et al.
7 May 2020, in The Lancet – Respiratory Medicine
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
Methods: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.

Interleukin-1 blockade with high-dose anakinra in patient swith COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study
Giulio Cavalli et al.
7 May 2020, in The Lancet – Rheumatology
Background : Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population.
Methods : We conducted a retrospective cohort study at the San Raffaele Hospital in Milan, Italy. We included consecutive patients (aged ≥18 years) with COVID-19, moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive protein ≥100 mg/L, ferritin ≥900 ng/mL, or both) who were managed with non-invasive ventilation outside of the ICU and who received standard treatment of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally. We compared survival, mechanical ventilation-free survival, changes in C-reactive protein, respiratory function, and clinical status in a cohort of patients who received additional treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) with a retrospective cohort of patients who did not receive anakinra (referred to as the standard treatment group).
All outcomes were assessed at 21 days.

A Peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019(COVID-19)
Xue-fei Cai et al.
8 May 2020, in The Journal of Infectious Diseases
SARS-CoV-2, a novel ß-coronavirus, cause severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named COVID-19. To date, real-time RT-PCR is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. Here, we developed a peptide-based luminescent immunoassay that detected immunoglobulin G (IgG) and IgM. The assay cut-off value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19

Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Joseph R. Fauver et al.
7 May 2020, in Cell
The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.

T cell subset counts in peripheral blood can be used as discriminatory biomarkers for diagnosis and severity prediction of COVID-19
Mei Jiang et al.
7 May 2020, in The Journal of Infectious Diseases
This study evaluated the significance of lymphocyte subsets detection in peripheral blood in the diagnosis and prognosis of coronavirus disease 2019 (COVID-19). Our results revealed that CD3+T, CD4+T, CD8+T cells and NK cells were significantly decreased in COVID-19 patients. COVID-19 patients had a relatively slight decrease in CD4+T cells but a severe decrease of CD8+T cells. The significantly elevated CD4/CD8 ratio was observed in COVID-19 patients. T cell subset counts were related to the severity and prognosis of COVID-19. The counts of CD8+T and CD4+T cells can be used as diagnostic markers of COVID-19 and predictors of disease severity.

Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19
Alisa Fox et al.
8 May 2020, in medRxiv
SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >3.2 million people, including >220,000 deaths. Human milk IgG originates mainly from blood, therefore a SARS-CoV-2-reactive antibody (Ab) response in milk would be expected (1). However, IgG comprises only ~2% of milk Ab, with most milk Abs originating from mucosa-associated lymphatic tissue (1). Therefore, the extent of the milk immune response to SARS-CoV-2 is unknown (2). This response is critical for infants and young children, who tend not to suffer greatly from COVID-19 pathology but are likely responsible for significant virus transmission (3-5). Perhaps even more significant is the fact that milk Abs could be purified and used as a COVID-19 therapeutic, given they would likely be of the secretory (s) class and highly resistant to proteolytic degradation in the respiratory tissue (2, 6). In this preliminary report, 15 milk samples obtained from donors previously-infected with SARS-CoV-2 as well as 10 negative control samples obtained prior to December 2019 were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein by ELISAs measuring IgA, IgG, IgM, and secretory Ab. Eighty percent of samples obtained post-COVID-19 exhibited IgA reactivity, and all these samples were also positive for secretory Ab reactivity, suggesting the IgA is predominantly sIgA. COVID-19 group mean OD values of undiluted milk were significantly greater for IgA (p<0.0001), secretory-type Abs (p<0.0001), and IgG (p=0.017), but not for IgM, compared to pre-pandemic group mean values. Overall, these data indicate that there is strong sIgA-dominant SARS-CoV-2 immune response in human milk after infection in the majority of individuals, and that a comprehensive study of this response is highly warranted.

Forecasting the spread of COVID-19 in Nigeria using Box-Jenkins Modeling Procedure
Rauf Rauf Ibrahim and Hannah Oluwakemi Oladipo
8 May 2020, in medRxiv
Objective: This study is focused on the analysis of the spread of Covid-19 in Nigeria, applying statistical models and available data from the NCDC. We present an insight into the spread of Covid-19 in Nigeria in order to establish a suitable prediction model, which can be applied as a decision-supportive tool for assigning health interventions and mitigating the spread of the Covid-19 infection.
Methodology: Daily spread data from February 27 to April 26, 2020, were collected to construct the autoregressive integrated moving average (ARIMA) model using the R software. Stability analysis and stationarity test, parameter test, and model diagnostic were also carried out. Finally, the fitting, selection and prediction accuracy of the ARIMA model was evaluated using the AICc model selection criteria.
Results: The ARIMA (1,1,0) model was finally selected among ARIMA models based upon the parameter test and Box–Ljung test. A ten-day forecast was also made from the model, which shows a steep upward trend of the spread of the COVID-19 in Nigeria within the selected time frame.

Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs
Atsushi Hijikata et al.
PMID: 32379896, 7 May 2020, in FEBS Press
The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus SARS‐CoV‐2 a pandemic. There is, however, no confirmed anti‐COVID‐19 therapeutic currently. In order to assist structure‐based discovery efforts for repurposing drugs against this disease, we constructed knowledge‐based models of SARS‐CoV‐2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID‐19.

Association Between ABO Blood Groups and Risk of SARS-CoV-2 Pneumonia
Juyi Li et al.
PMID: 32379894, 7 May 2020, in Brithish Journal of Haematology
In December, 2019, a cluster of acute respiratory illness caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China.1,2 Epidemiological, clinical characteristics, risk factors for mortality of patients infected with SARS-CoV-2, and risk factors in the susceptibility to SARS-CoV-2 included age and chronic disease have been reported.

Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization
Vikas Peddu et al.
PMID: 32379863, 7 May 2020, in Clinical Chemistry
Background: More than two months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence.
Methods: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2.


 

7 May, 2020, 15.00 CET

 

Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur
Zhenming Jin et al.
7 May 2020, in Nature Structural & Molecular Biology
The antineoplastic drug carmofur is shown to inhibit the SARS-CoV-2 main protease (Mpro). Here, the X-ray crystal structure of Mpro in complex with carmofur reveals that the carbonyl reactive group of carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50= 24.30 μM) and is a promising lead compound to develop new antiviral treatment for COVID-19.

 

Modeling shield immunity to reduce COVID-19 epidemic spread
Joshua S. Weitz et al.
7 May 2020, in Nature Medicine
The COVID-19 pandemic has precipitated a global crisis, with more than 1,430,000 confirmed cases and more than 85,000 confirmed deaths globally as of 9 April 20201. Mitigation and suppression of new infections have emerged as the two predominant public health control strategies . Both strategies focus on reducing new infections by limiting human-to-human interactions, which could be both socially and economically unsustainable in the long term. We have developed and analyzed an epidemiological intervention model that leverages serological tests to identify and deploy recovered individuals as focal points for sustaining safer interactions via interaction substitution, developing what we term ‘shield immunity’ at the population scale. The objective of a shield immunity strategy is to help to sustain the interactions necessary for the functioning of essential goods and services while reducing the probability of transmission. Our shield immunity approach could substantively reduce the length and reduce the overall burden of the current outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well-recognized roles in estimating prevalence and in the potential development of plasma-based therapies.

 

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice
Linlin Bao et al.
7 May 2020, in Nature
Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern . Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of signifcant macrophages and lymphocytes into the alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, macrophages and alveolar epithelia. The phenomenon was not found in wild-type mice with SARS-CoV-2 infection. Notably, we have confrmed the pathogenicity of SARS-CoV-2 in hACE2 mice. The mouse model with SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutics and vaccines as well as understanding the pathogenesis of COVID-19.

 

Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins
Kangpeng Xiao et al.
7 May 2020, in Nature
The outbreak of COVID-19 poses unprecedent challenges to global health . The new coronavirus, SARS-CoV-2, shares high sequence identity to SARS-CoV and a bat coronavirus RaTG13. While bats may be the reservoir host for various coronaviruses , whether SARS-CoV-2 has other hosts remains ambiguous. In this study, one coronavirus isolated from a Malayan pangolin showed 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S genes, respectively. In particular, the receptor-binding domain within the S protein of the Pangolin-CoV is virtually identical to that of SARS-CoV-2, with one noncritical amino acid diference. Results of comparative genomic analysis suggest that SARS-CoV-2 might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. The Pangolin-CoV was detected in 17 of 25 Malayan pangolins analyzed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against Pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus that is highly related to SARS-CoV-2 in pangolins suggests that they have the potential to act as the intermediate host of SARS-CoV-2. The newly identifed coronavirus in the most-trafficked mammal could represent a future threat to public health if wildlife trade is not effectively controlled.

 

Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages
Miriam Merad and Jerome C. Martin
6 May 2020, in Nature Reviews Immunology
The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-1.

 

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
B. Cao et al.
7 May 2020, in NEJM
BACKGROUND No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.
METHODS We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2 ) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2 ) to the fraction of inspired oxygen (Fio2 ) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

 

Characteristics of doctors’ fatality due to COVID-19 in Western Europe and Asia Pacific countries
Izumi Yoshida et al.
6 May 2020, in QJM : An International Journal of Medicine
Under the COVID-19 pandemic, the deaths of healthcare professionals have been increasingly reported worldwide. We performed a cross-sectional, observational study using news reports on the websites among selected countries as of April, 2020. We found 120 dead medical doctors due to COVID-19 in Western Europe and Asia-Pacific countries; 67 in Italy (47 in the Northern part), 34 in China (22 in Hubei), 6 in France, 4 in the UK, the US, and Spain, and 1 in South Korea, respectively. Among them, 90% were men, and specialities were reported as general practitioners for 30% and as physicians for 11.6%. The overall proportions of dead medical doctors amounted to 1.9 per 10,000 confirmed cases and 30.2 per 10,000 dead cases, respectively. Proactive measures are warranted to protect doctors especially those who often have encounters with COVID-19 patients.

 

COVID-2019 associated over-expressed Prevotella proteins mediated host-pathogen interactions and their role in coronavirus outbreak
Abdul Arif Khan and Zakir Khan
6 May 2020, in Bioinformatics
The outbreak of COVID-2019 initiated at Wuhan, China has become a global threat by rapid transmission and severe fatalities. Recent studies have uncovered whole genome sequence of SARS-CoV-2 (causing COVID-2019). In addition, lung metagenomic studies on infected patients revealed overrepresented Prevotella spp. producing certain proteins in abundance. We performed host-pathogen protein-protein interaction analysis between SARS-CoV-2 and overrepresented Prevotella proteins with human proteome. We also performed functional overrepresentation analysis of interacting proteins to understand their role in COVID-2019 severity.

 

A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2
Yan Wu et al.
7 May 2020, in medRxiv
Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design.

 

Effects of Coronavirus Disease 2019 (COVID-19) on Maternal, Perinatal and Neonatal Outcomes: a Systematic Review of 266 Pregnancies
Juan Juan et al.
6 May 2020, in medRxiv
Objective: To perform a systematic review of available published literature on pregnancies affected by COVID-19 to evaluate the effects of COVID-19 on maternal, perinatal and neonatal outcomes.
Methods: We performed a systematic review to evaluate the effects of COVID-19 on pregnancy, perinatal and neonatal outcomes. We conducted a comprehensive literature search using PubMed, EMBASE, Cochrane library, China National Knowledge Infrastructure Database and Wan Fang Data until April 20, 2020 (studies were identified through PubMed alert after April 20, 2020). For the research strategy, combinations of the following keywords and MeSH terms were used: SARS-CoV-2, COVID-19, coronavirus disease 2019, pregnancy, gestation, maternal, mothers, vertical transmission, maternal-fetal transmission, intrauterine transmission, neonates, infant, delivery. Eligibility criteria included laboratory-confirmed and/or clinically diagnosed COVID-19, patient was pregnant on admission, availability of clinical characteristics, including maternal, perinatal or neonatal outcomes. Exclusion criteria were unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, and unreported maternal or perinatal outcomes.
No language restrictions were applied.

 

A systematic review and meta-analysis of published research data on COVID-19 infection-fatality rates
Gideon Meyerowitz-Katz and Lea Merone
6 May 2020, in medRxiv
Introduction: An important unknown during the COVID-19 pandemic has been the infection-fatality rate (IFR). This differs from the case-fatality rate (CFR) as an estimate of the number of deaths as a proportion of the total number of cases, including those who are mild and asymptomatic. While the CFR is extremely valuable for experts, IFR is increasingly being called for by policy-makers and the lay public as an estimate of the overall mortality from COVID-19.
Methods: Pubmed and Medrxiv were searched using a set of terms and Boolean operators on 25/04/2020. Articles were screened for inclusion by both authors. Meta-analysis was performed in Stata 15.1 using the metan command, based on IFR and confidence intervals extracted from each study. Google/Google Scholar was used to assess the grey literature relating to government reports. 

 

Infection prevention and control compliance in Tanzanian out patient facilities: a cross-sectional study with implications for the control of COVID-19
Timothy Powell-Jackson et al.
6 May 2020, in The Lancet Global Health
Background : As coronavirus disease 2019 (COVID-19) spreads, weak health systems must not become a vehicle for transmission through poor infection prevention and control practices. We assessed the compliance of health workers with infection prevention and control practices relevant to COVID-19 in outpatient settings in Tanzania, before the pandemic.
Methods : This study was based on a secondary analysis of cross-sectional data collected as part of a randomised controlled trial in private for-profit dispensaries and health centres and in faith-based dispensaries, health centres, and hospitals, in 18 regions. We observed provider–patient interactions in outpatient consultation rooms, laboratories, and dressing rooms, and categorised infection prevention and control practices into four domains: hand hygiene, glove use, disinfection of reusable equipment, and waste management. We calculated compliance as the proportion of indications (infection risks) in which a health worker performed a correct action, and examined associations between compliance and health worker and facility characteristics using multilevel mixed-effects logistic regression models.

 

Acute Cor Pulmonale in Critically Ill Patients With Covid-19
Christina Creel-Bulos et al.
PMID: 32374956, 6 May 2020, in NEJM
We describe five patients in our intensive care units (ICUs) who had confirmed Covid-19. All five patients presented to the ICUs between March 23 and April 4, 2020. Four of the five patients had profound hemodynamic instability and cardiac arrest with acute right ventricular failure, and one had severe hemodynamic instability without cardiac arrest. The clinical scenario and echocardiographic findings in one representative patient are provided (see the Video, available with the full text of this case at NEJM.org).

 

Detection of the Middle East Respiratory Syndrome Coronavirus in Dromedary Camel's Seminal Plasma in Saudi Arabia 2015-2017
Maged Gomaa Hemida et al.
PMID: 32374945, 6 May 2020, in Transboundary and Emerging Diseases
The Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emergent respiratory virus. Dromedary camels are currently the only known reservoir of MERS‐CoV and are capable of transmitting the virus within a herd. The role of semen in the transmission of MERS‐CoV has never been investigated as yet, to the best of our knowledge. Our goal was to test semen collected from dromedary camels for MERS‐CoV. A total of 67 seminal plasma samples from infertile and 13 from fertile dromedary camels was collected. The RNA was extracted from the samples and tested using commercial real‐time PCR. Nine out of sixty‐seven infertile animals (13.4%) were positive. The obtained PCR products were sequenced using the conserved MERS‐CoV‐N gene primers. MERS‐CoV‐RNA detected in seminal plasma was closely related to the lineage B. To the best of our knowledge, this is the first report about the detection of MERS‐CoV‐RNA in camel’s seminal plasma. Regular testing of semen of common male camels' used for insemination should be considered to avoid a possible spread of the virus through semen.

 

Autoimmune hemolytic anemia associated with Covid‐19 infection
Gregory Lazarian et al.
6 May 2020, in British Journal of Haematology
Among patients with SARS‐CoV‐2 infection (also known as Covid‐19), pneumonia, respiratory failure, and acute respiratory distress syndrome are frequently encountered complications (Zhou et al, 2020). Although the pathophysiology underlying severe Covid‐19 remains poorly understood, accumulating evidence argue for hyperinflammatory syndrome causing fulminant and fatal cytokines release associated with disease severity and poor outcome (Mehta et al, 2020). However, the spectrum of complications is broader and include among others various auto‐immune disorders such as autoimmune thrombocytopenia, Guillain‐Barré and antiphospholipid syndrome (Zhang et al, 2020; Zulfiqar et al, 2020; Toscano et al, 2020). In this report we describe 7 patients from 6 French and Belgian Hospitals who developed a first episode of autoimmune hemolytic anemia (AIHA) during a Covid‐19 infection.

 

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study
Dominic Wichmann et al.
PMID: 32374815, 6 May 2020, in Annals of Internal Medicine
Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features.
Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.
Design: Prospective cohort study.
Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.
Patients: The first 12 consecutive COVID-19-positive deaths.
Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.

 

06 May, 2020, 12.45 CET

Using Data To Find a Balance
5 May 2020, PERC
In this report, the Partnership for Evidence Based Response to COVID-19 (PERC), a consortium of global public health organizations and private sector firms, brings together findings from a survey conducted March 29-April 17, 2020 in 28 cities across 20 AU Member States, along with epidemiological measures of disease transmission and indicators of population movements and unrest, among others. Synthesized, these data provide a first-of-its-kind snapshot of baseline conditions in Africa during this rapidly evolving pandemic.

 

Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2
Kazuma Kiyotani et al.
6 May 2020, in Journal of Human Genetics
To control and prevent the current COVID-19 pandemic, the development of novel vaccines is an emergent issue. In addition, we need to develop tools that can measure/monitor T-cell and B-cell responses to know how our immune system is responding to this deleterious virus. However, little information is currently available about the immune target epitopes of novel coronavirus (SARS-CoV-2) to induce host immune responses. Through a comprehensive bioinformatic screening of potential epitopes derived from the SARS-CoV-2 sequences for HLAs commonly present in the Japanese population, we identified 2013 and 1399 possible peptide epitopes that are likely to have the high affinity (<0.5%- and 2%-rank, respectively) to HLA class I and II molecules, respectively, that may induce CD8+ and CD4+ T-cell responses. These epitopes distributed across the structural (spike, envelope, membrane, and nucleocapsid proteins) and the nonstructural proteins (proteins corresponding to six open reading frames); however, we found several regions where high-affinity epitopes were significantly enriched. By comparing the sequences of these predicted T cell epitopes to the other coronaviruses, we identified 781 HLA-class I and 418 HLA-class II epitopes that have high homologies to SARS-CoV. To further select commonly-available epitopes that would be applicable to larger populations, we calculated population coverages based on the allele frequencies of HLA molecules, and found 2 HLA-class I epitopes covering 83.8% of the Japanese population. The findings in the current study provide us valuable information to design widely-available vaccine epitopes against SARS-CoV-2 and also provide the useful information for monitoring T-cell responses.

 

Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)
Neil Mehta et al.
5 May 2020, in JAMA Cardiology
Importance :The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use.
Objective : To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation).
Design, Setting, and Participants : Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included.

 

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies
Daniel Wrapp et al.
5 May 2020, in Cell
Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

 

Occurrence, prevention, and management of the psychologicaleffects of emerging virus outbreaks on healthcare workers:rapid review and meta-analysis
Steve Kisely et al.
5 May 2020, in BMJ
OBJECTIVE : To examine the psychological effects on clinicians of working to manage novel viral outbreaks, and successful measures to manage stress and psychological distress.
DESIGN : Rapid review and meta-analysis.
DATA SOURCES Cochrane Central Register of Controlled Trials, PubMed/Medline, PsycInfo, Scopus, Web of Science, Embase, and Google Scholar, searched up to late March 2020.
ELIGIBILITY CRITERIA FOR STUDY SELECTION Any study that described the psychological reactions of healthcare staff working with patients in an outbreak of any emerging virus in any clinical setting, irrespective of any comparison with other clinicians or the general population.

 

Impact of ethnicity on outcome of severe COVID-19 infection. Data from an ethnically diverse UK tertiary centre
James TH Teo et al.
6 May 2020, in medRxiv
During the current COVID-19 pandemic, anecdotal reports suggest that BAME background patients may be disproportionately affected compared to White but few objective data are available. We took advantage of near real-time hospital data access and analysis pipelines to look at the impact of ethnicity in 437 consecutive patients admitted during March to King’s College Hospital NHS Trust in London.

 

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19
Sachin J. Shah et al.
6 May 2020, in medRxiv
Background: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses.
Methods: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury).

 

Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2and MX1 Genes
Chandrika Bhattacharyya et al.
5 May 2020, in bioRxiv
COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other preexisting subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.

 

SARS-CoV-2 Spike Glycoprotein Receptor Binding Domain is Subject to Negative Selection with Predicted Positive Selection Mutations
You Li et al.
5 May 2020, in bioRxiv
COVID-19 is a highly contagious disease caused by a novel coronavirus SARS-CoV-2. The interaction between SARS-CoV-2 spike protein and the host cell surface receptor ACE2 is responsible for mediating SARS-CoV-2 infection. By analyzing the spike-hACE2 interacting surface, we predicted many hot spot residues that make major contributions to the binding affinity. Mutations on most of these residues are likely to be deleterious, leading to less infectious virus strains that may suffer from negative selection. Meanwhile, several residues with mostly advantageous mutations have been predicted. It is more probable that mutations on these residues increase the transmission ability of the virus by enhancing spike-hACE2 interaction. So far, only a limited number of mutations has been reported in this region. However, the list of hot spot residues with predicted downstream effects from this study can still serve as a tracking list for SARS-CoV-2 evolution studies. Coincidentally, one advantageous mutation, p.476G>S, started to surge in the last couple of weeks based on the data submitted to the public domain, indicating that virus strains with increased transmission ability may have already spread.

 

Selectomic and Evolvability Analyses of the Highly Pathogenic Betacoronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV
Meghan May et al.
5 May 2020, in bioRxiv
SARS-CoV-2, the causative agent of COVID-19, is widespread in several countries around the world following its late-2019 emergence in the human population. Rapid development of molecular diagnostic tests and subunit vaccines have been prioritized, and as such evaluating the SARS-CoV-2 genomic plasticity and evolutionary dynamics is an urgent need. We determined the SARS-CoV-2 selectome by calculating rates of pervasive and episodic diversifying selection for every amino acid coding position in the SARS-CoV-2 genome. To provide context for evolutionary dynamics of a highly pathogenic betacoronavirus following a zoonotic spillover into human hosts, we also determined the selectomes of SARS-CoV and MERS-CoV, and performed evolvability calculations for SARS-CoV-2 based on SARS-CoV. These analyses identify the amino acid sites within each coding sequence that have been subjected to pervasive diversifying selection or episodic diversifying selection, and report significantly evolvable sites in the ORF1a polyprotein, the spike protein, and the membrane protein of SARS-CoV-2. These findings provide a comprehensive view of zoonotic, highly pathogenic betacoronavirus evolutionary dynamics that can be directly applied to diagnostic assay and vaccine design for SARS-CoV-2.

 

Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Asif Naeem et al.
PMID: 32370153, 2 May 2020, in Viruses
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a lethal zoonotic pathogen circulating in the Arabian Peninsula since 2012. There is no vaccine for MERS and anti-viral treatment is generally not applicable. We investigated the evolution of the MERS-CoV spike gene sequences and changes in viral loads over time from patients in Saudi Arabia from 2105-2017. All the MERS-CoV strains belonged to lineage 5, and showed high sequence homology (99.9%) to 2017 strains. Recombination analysis showed a potential recombination event in study strains from patients in Saudi Arabia. The spike gene showed eight amino acid substitutions, especially between the A1 and B5 lineage, and contained positively selected codon 1020. We also determined that the viral loads were significantly (p < 0.001) higher in fatal cases, and virus shedding was prolonged in some fatal cases beyond 21 days.

 

Incidence of Venous Thromboembolism in Hospitalized Patients With COVID-19
Saskia Middeldorp et al.
PMID: 32369666, 5 May 2020, in Journal of Thrombosis and Haemostasis
Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. We investigated the incidence of objectively confirmed venous thromboembolism (VTE) in 198 hospitalized patients with COVID-19 in a single-center cohort study. Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.

 

Thrombocytopenia as an Initial Manifestation of Covid-19; Case Series and Literature Review
Maria Zahid Ahmed et al.
PMID : 32369609, 5 May 2020, in British Journal of Haematology
Covid-19 has emerged as a global threat that has claimed millions of lives until now. Haematological manifestation as an initial presentation of this deadly virus is not frequently reported in the literature. We hereby report a case series of asymptomatic patients with severe thrombocytopenia which was later found to be Covid induced.

 

05 May, 2020, 16.30 CET

Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing
Wen Wen et al.
4 May 2020, in Cell Discovery
COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19.

 

Effect of non-pharmaceutical interventions to contain COVID-19 in China
Shengjie Lai et al.
4 May 2020, in Nature
On March 11, 2020, the World Health Organization declared COVID-19 a pandemic1 . The outbreak containment strategies in China based on non-pharmaceutical interventions (NPIs) appear to be efective2 , but quantitative research is still needed to assess the efcacy of NPIs and their timings3 . Using epidemiological and anonymised human movement data4,5 , here we develop a modelling framework that uses daily travel networks to simulate diferent outbreak and intervention scenarios across China. We estimated that there were a total of 114,325 COVID-19 cases (interquartile range 76,776 - 164,576) in mainland China as of February 29, 2020. Without NPIs, the COVID-19 cases would likely have shown a 67-fold increase (interquartile range 44 - 94) by February 29, 2020, with the efectiveness of diferent interventions varying. The early detection and isolation of cases was estimated to have prevented more infections than travel restrictions and contact reductions, but combined NPIs achieved the strongest and most rapid efect. The lifting of travel restrictions since February 17, 2020 does not appear to lead to an increase in cases across China if the social distancing interventions can be maintained, even at a limited level of 25% reduction on average through late April. Our fndings contribute to an improved understanding of NPIs on COVID-19 and to inform response eforts across the World.

 

The continued threat of emerging flaviviruses
Theodore C. Pierson and Michael S. Diamond
4 May 2020, in Nature Microbiology
Flaviviruses are vector-borne RNA viruses that can emerge unexpectedly in human populations and cause a spectrum of potentially severe diseases including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, congenital abnormalities and fetal death. This epidemiological pattern has occurred numerous times during the last 70 years, including epidemics of dengue virus and West Nile virus, and the most recent explosive epidemic of Zika virus in the Americas. Flaviviruses are now globally distributed and infect up to 400 million people annually. Of significant concern, outbreaks of other less well-characterized flaviviruses have been reported in humans and animals in different regions of the world. The potential for these viruses to sustain epidemic transmission among humans is poorly understood. In this Review, we discuss the basic biology of flaviviruses, their infectious cycles, the diseases they cause and underlying host immune responses to infection. We describe flaviviruses that represent an established ongoing threat to global health and those that have recently emerged in new populations to cause significant disease. We also provide examples of lesser-known flaviviruses that circulate in restricted areas of the world but have the potential to emerge more broadly in human populations. Finally, we discuss how an understanding of the epidemiology, biology, structure and immunity of flaviviruses can inform the rapid development of countermeasures to treat or prevent human infections as they emerge.

A human monoclonal antibody blocking SARS-CoV-2 infection
Chunyan Wang et al.
4 May 2020, in Nature Communications

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

 

Site-specific glycan analysis of the SARS-CoV-2 spike
Yasunori Watanabe et al.
4 May 2020, in Science
The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycanprocessing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.

 

Estimation of the basic reproduction number, average incubation time, asymptomatic infection rate, and case fatality rate for COVID-19: Meta-analysis and sensitivity analysis
Wenqing He et al.
5 May 2020, in medRxiv
The coronavirus disease 2019 (COVID-19) has been found to be caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, comprehensive knowledge of COVID-19 remains incomplete and many important features are still unknown. This manuscripts conduct a meta-analysis and a sensitivity study to answer the questions: What is the basic reproduction number? How long is the incubation time of the disease on average? What portion of infections are asymptomatic? And ultimately, what is the case fatality rate? Our studies estimate the basic reproduction number to be 3.15 with the 95% interval (2.41, 3.90), the average incubation time to be 5.08 days with the 95% confidence interval (4.77, 5.39) (in day), the asymptomatic infection rate to be 46% with the 95% confidence interval (18.48%, 73.60%), and the case fatality rate to be 2.72% with 95% confidence interval (1.29%, 4.16%) where asymptomatic infections are accounted for.

 

Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2
Dachun Xu et al.
5 May 2020, in medRxiv
The coronavirus disease 2019 (COVID-19) has resulted in high morbidity and mortality worldwide since December 2019. Recent studies showed that patients with previous heart disease, especially heart failure (HF), whose plasma Natriuretic Peptides (NPs) concentrations are higher, were more susceptible to SARS-CoV-2 infection. In this study, we retrospectively analyzed single-center case series of 91 patients with COVID-19 in China. 46 (50.5%) patients exhibited cardiac dysfunction as indicated by elevated Natriuretic Peptides B (BNP) levels. Moreover, the results indicate that patients with cardiac dysfunction had higher mortality than those without cardiac dysfunction. Nonetheless, it remains unclear as to how the virus infects the heart, especially in HF patients and why a higher level of BNP in the heart dampen inflammation. Angiotensin-converting enzyme 2 (ACE2), the critical host cellular receptor of SARS-CoV-2, expresses in different organs. Still, its cellular distribution in the human heart, especially in patients with HF remains unclear. Thus, we investigated ACE2 gene expression pattern in single-cell RNA sequence (scRNA-seq) data of hearts from normal adults versus patients with HF.

 

First case of placental infection with SARS-CoV-2
Hillary Hosier et al.
5 May 2020, in medRxiv
Background : The effects of Covid-19 in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic Covid-19 complicated by severe preeclampsia and placental abruption. Methods : We analyzed placenta for the presence of SARS-CoV-2 through molecular and immunohistochemical assays and by and electron microscopy, and we measured the maternal antibody response in blood to this infection.

 

Potential influence of COVID-19/ACE2 on the female reproductive system
Yan Jing et al.
4 May 2020, in Molecular Human Reproduction
The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.

 

Post-mortem Examination of COVID19 Patients Reveals Diffuse Alveolar Damage With Severe Capillary Congestion and Variegated Findings of Lungs and Other Organs Suggesting Vascular Dysfunction
T. Menter et al.
PMID: 32364264, 4 May 2020, in Histopathology
Aims: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations.
Methods: This study reports autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety
.

 

Identification of a Novel Coronavirus Causing Severe Pneumonia in Human: A Descriptive Study
Li-Li Ren et al.
PMID: 32004165, 4 May 2020, in Chinese Medical Journal
Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.

 

Analysis of Factors Associated With Disease Outcomes in Hospitalized Patients With 2019 Novel Coronavirus Disease
Wei Liu et al.
PMID: 32118640, 4 May 2020, in Chinese Medical Journal
Background: Since early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.
Methods: Patients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher's exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.

 

Distribution of the COVID-19 Epidemic and Correlation With Population Emigration From Wuhan, China
Ze-Liang Chen et al.
PMID: 32118644, 4 May 2020, in Chinese Medical Journal
Background: The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.
Methods: The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed.

 

Studies on Viral Pneumonia Related to Novel Coronavirus SARS-CoV-2, SARS-CoV, and MERS-CoV: A Literature Review
Guo Liya et al.
PMID: 32363707, 4 May 2020, in APMIS Journal of Pathology, Microbiology and Immunology
Coronaviruses are a class of RNA viruses that can cause respiratory and intestinal infections in animals and humans. SARS-CoV, MERS-CoV and a novel coronavirus (SARS-CoV-2 [2019-nCoV]) belong to the family Coronaviridae and the genus Betacoronavirus. At present, the understanding of SARS-CoV-2 is getting deeper and deeper. In order to better prevent and treat SARS-CoV-2, this article compares the infectivity, pathogenicity, and related clinical characteristics of the three human pathogenic coronaviruses, SARS-CoV-2, SARS-CoV and MERS-CoV to help us further understand the pathogenic characteristics of novel coronaviruses.

 

 

04 May, 2020, 15.00 CET

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
David E. Gordon et al.
30 April 2020, in Nature
The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

 

Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
Mandeep R. Mehra et al.
1 May 2020, in The New England Journal of Medicine
BACKGROUND : Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS : Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020.

 

Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19
Giuseppe Mancia et al.
1 May 2020, in The New England Journal of Medicine
BACKGROUND : A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting–enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.
METHODS : We carried out a population-based case–control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.

 

Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19
Harmony R. Reynolds et al.
1 May 2020, in The New England Journal of Medicine
BACKGROUND : There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
METHODS We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)
Ruiyun Li et al.
1 May 2020, in Science
Estimation of the prevalence and contagiousness of undocumented novel coronavirus [severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2)] infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here, we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model, and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV-2, including the fraction of undocumented infections and their contagiousness. We estimate that 86% of all infections were undocumented [95% credible interval (CI): 82–90%] before the 23 January 2020 travel restrictions. The transmission rate of undocumented infections per person was 55% the transmission rate of documented infections (95% CI: 46–62%), yet, because of their greater numbers, undocumented infections were the source of 79% of the documented cases. These findings explain the rapid geographic spread of SARS-CoV-2 and indicate that containment of this virus will be particularly challenging.

The effect of human mobility and control measures on the COVID-19 epidemic in China
Moritz U. G. Kraemer et al.
1 May 2020, in Science
The ongoing coronavirus disease 2019 (COVID-19) outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions were undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We used real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. After the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.

Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
Wanchao Yin et al.
1 May 2020, in Science
The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug, Remdesivir. Here we report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Å resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 Å resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is covalently incorporated into the primer strand at the first replicated base pair and terminates chain elongation. Our structures provide critical insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.

SARS-CoV-2 productively infects human gut enterocytes
Mart M. Lamers et al.
1 May 2020, in Science
The virus severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) can cause coronavirus disease 2019 (COVID-19), an influenza-like disease that is primarily thought to infect the lungs with transmission via the respiratory route. However, clinical evidence suggests that the intestine may present another viral target organ. Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes. In human small intestinal organoids (hSIOs), enterocytes were readily infected by SARS-CoV and SARS-CoV-2 as demonstrated by confocal- and electron-microscopy. Consequently, significant titers of infectious viral particles were detected. mRNA expression analysis revealed strong induction of a generic viral response program. Hence, intestinal epithelium supports SARS-CoV-2 replication, and hSIOs serve as an experimental model for coronavirus infection and biology.

Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China
Juanjuan Zhang et al.
29 April 2020, in Science
Intense non-pharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-8-fold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0-14 years are less susceptible to SARS-CoV-2 infection than adults 15-64 years of age (odd ratio 0.34, 95%CI 0.24-0.49), while in contrast, individuals over 65 years are more susceptible to infection (odd ratio 1.47, 95%CI: 1.12-1.92). Based on these data, we build a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.

Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit
Francis Bessière et al.
1 May 2020, in JAMA Cardiology
The novel coronavirus disease 2019 (COVID-19) outbreak is an ongoing situation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 Studies in patients with mild to moderate COVID-19 symptoms have suggested benefits of hydroxychloroquine alone or in combination with azithromycin against SARS-CoV-2 and raised hope for treating the disease.2 As a result, these treatments are increasingly used off-label for patients with COVID-19, including for those in intensive care units (ICUs).2,3 However, both medications are known to induce QT prolongation via a human Ether-à-go-go–related gene potassium channel blockade, which can promote life-threatening ventricular arrhythmias.4,5 Safety data for these treatments are largely lacking for patients with COVID-19. This is even more relevant for critically ill patients who are particularly exposed to electrolyte imbalance and/or drugs leading to an increased risk of QT prolongation.6 Therefore, we aimed to examine the safety of hydroxychloroquine with or without azithromycin regarding QT interval in ICU patients with COVID-19.

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset
Hao-Yuan Cheng et al.
1 May 2020, in JAMA Internal Medicine
Importance :The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies.
Objective :To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset.
Design, Setting, and Participants : This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020.
Main Outcomes and Measures :Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care).

Deducing the N- and O- glycosylation profile of the spike protein ofnovel coronavirus SARS-CoV-2
Asif Shajahan et al.
4 May 2020, in Glycobiology
The current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O- glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate.

Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China
Ling Hu et al.
3 May 2020, in Clinical Infectious Diseases
Background : With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes.
Methods : A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression.

Evaluation of COVID-19 RT-qPCR test in multi-sample pools
Idan Yellin et al.
2 May 2020, in Clinical Infectious Diseases
Background : The recent emergence of SARS-CoV-2 lead to a current pandemic of unprecedented scale. Though diagnostic tests are fundamental to the ability to detect and respond, overwhelmed healthcare systems are already experiencing shortages of reagents associated with this test, calling for a lean immediately-applicable protocol.
Methods : RNA extracts of positive samples were tested for the presence of SARS-CoV-2 using RT-qPCR, alone or in pools of different sizes (2-, 4-, 8- ,16-, 32- and 64-sample pools) with negative samples. Transport media of additional 3 positive samples were also tested when mixed with transport media of negative samples in pools of 8.

Longitudinal Change of SARS-Cov2 Antibodies in Patients with COVID-19
Guoxin Zhang et al.
2 May 2020, in The Journal of Infectious Diseases
Background :  A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide.
Methods. We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between February 1 and February 29, 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen.

Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geodistribution and a rich genetic variations of hotspots mutations
Meriem Laamarti et al.
3 May 2020, in bioRxiv
In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating their spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 59 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored.

Isolating multiple formats of human monoclonal neutralizing antibodies against SARS-CoV-2 by in vitro site-directed antibody screening
Xiaoyu Liu et al.
3 May 2020, in bioRxiv
Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells.

Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route
Lehai Zhang et al.
3 May 2020, in medRxiv
In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis.

Better Strategies for Containing COVID-19 Epidemics --- A Study of 25 Countries via an Extended Varying Coefficient SEIR Model
Jia Gu et al.
3 May 2020, in medRxiv
We evaluate the effectiveness of COVID-19 control strategies of 25 countries which have endured more than four weeks of community infections. With an extended SEIR model that allows infections in both the exposed and infected states, the key epidemic parameters are estimated from each country's data, which facilitate the evaluation and cross-country comparison. It is found quicker control measures significantly reduce the average reproduction numbers and shorten the time length to infection peaks. If the swift control measures of Korea and China were implemented, average reductions of 88% in the confirmed cases and 80% in deaths would had been attained for the other 23 countries from start to April 10. Effects of earlier or delayed interventions in the US and the UK are experimented which show at least 75% (29%) less infections and deaths can be attained for the US (the UK) under a Five-Day Earlier experiment. The impacts of two removal regimes (Korea and Italy) on the total infection and death tolls on the other countries are compared with the naturally forecast ones, which suggest there are still ample opportunity for countries to reduce the final death numbers by improving the removal process.

Neonatal Late Onset Infection With Severe Acute Respiratory Syndrome Coronavirus 2
Danilo Buonsenso et al.
PMID: 32359227, 2 May 2020, in American Journal of Perinatology
Objective: To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2.
Study design: This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19).
Results: Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic.

A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19
Md Sadakat Chowdhury et al.
PMID: 32359203, 2 May 2020, in Academic Emergency Medicine
Background: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, Chloroquine (CQ) and derivative, Hydroxychloroquine (HCQ), have garnered the most attention.
Methods: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Librar, MedRxiv and 1 clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0.

Evaluation of COVID-19 RT-qPCR test in multi-sample pools
Idan Yelin et al.
PMID: 32358960, 2 May 2020, in Clinical Infectious Diseases
Background: The recent emergence of SARS-CoV-2 lead to a current pandemic of unprecedented scale. Though diagnostic tests are fundamental to the ability to detect and respond, overwhelmed healthcare systems are already experiencing shortages of reagents associated with this test, calling for a lean immediately-applicable protocol.
Methods: RNA extracts of positive samples were tested for the presence of SARS-CoV-2 using RT-qPCR, alone or in pools of different sizes (2-, 4-, 8- ,16-, 32- and 64-sample pools) with negative samples. Transport media of additional 3 positive samples were also tested when mixed with transport media of negative samples in pools of 8.

Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19:a cohort study in Wuhan, China
Kun Wang et al.
PMID : 32361723, 3 May 2020, in Clinical Infectious Diseases
Background: This study aimed to develop mortality-prediction models for patients with Coronavirus disease 2019 (COVID-19).
Methods: The training cohort were consecutive patients with COVID-19 in the First People's Hospital of Jiangxia District in Wuhan from January 7, 2020 to February 11, 2020. We selected baseline clinical and laboratory data through the stepwise Akaike information criterion and ensemble XGBoost model to build mortality-prediction models. We then validated these models by randomly collecting COVID-19 patients in the Infection department of Union Hospital in Wuhan from January 1, 2020, to February 20, 2020.

 

30 April, 2020, 14.30 CET

Genetic diversity and ecology of coronaviruses hosted by cave dwelling bats in Gabon
Gael Darren Maganga et al.
30 April 2020, in Scientific Reports
Little research on coronaviruses has been conducted on wild animals in Africa. Here, we screened a wide range of wild animals collected in six provinces and five caves of Gabon between 2009 and 2015. We collected a total of 1867 animal samples (cave-dwelling bats, rodents, non-human primates and other wild animals). We explored the diversity of CoVs and determined the factors driving the infection of CoVs in wild animals. Based on a nested reverse transcription-polymerase chain reaction, only bats, belonging to the Hipposideros gigas (4/156), Hipposideros cf. ruber (13/262) and Miniopterus infatus (1/249) species, were found infected with CoVs. We identifed alphacoronaviruses in H. gigas and H. cf. ruber and betacoronaviruses in H. gigas. All Alphacoronavirus sequences grouped with Human coronavirus 229E (HCoV-229E). Ecological analyses revealed that CoV infection was signifcantly found in July and October in H. gigas and in October and November in H. cf ruber. The prevalence in the Faucon cave was significantly higher. Our findings suggest that insectivorous bats harbor potentially zoonotic CoVs; highlight a probable seasonality of the infection in cave-dwelling bats from the North-East of Gabon and pointed to an association between the disturbance of the bats’ habitat by human activities and CoV infection.

 

Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus
Arinjay Banerjee et al.
29 April 2020, in Scientific Reports
Coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are speculated to have originated in bats. The mechanisms by which these viruses are maintained in individuals or populations of reservoir bats remain an enigma. Mathematical models have predicted long-term persistent infection with low levels of periodic shedding as a likely route for virus maintenance and spillover from bats. In this study, we tested the hypothesis that bat cells and MERS coronavirus (CoV) can co-exist in vitro. To test our hypothesis, we established a long-term coronavirus infection model of bat cells that are persistently infected with MERS-CoV. We infected cells from Eptesicus fuscus with MERS-CoV and maintained them in culture for at least 126 days. We characterized the persistently infected cells by detecting virus particles, protein and transcripts. Basal levels of type I interferon in the long-term infected bat cells were higher, relative to uninfected cells, and disrupting the interferon response in persistently infected bat cells increased virus replication. By sequencing the whole genome of MERS-CoV from persistently infected bat cells, we identifed that bat cells repeatedly selected for viral variants that contained mutations in the viral open reading frame 5 (ORF5) protein. Furthermore, bat cells that were persistently infected with ΔORF5 MERS-CoV were resistant to superinfection by wildtype virus, likely due to reduced levels of the virus receptor, dipeptidyl peptidase 4 (DPP4) and higher basal levels of interferon in these cells. In summary, our study provides evidence for a model of coronavirus persistence in bats, along with the establishment of a unique persistently infected cell culture model to study MERS-CoV-bat interactions.

 

Clinical Characteristics of Coronavirus Disease 2019 in China
Wei-jie Guan et al.
30 April 2020, in The New England Journal of Medicine
BACKGROUND : Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.
METHODS : We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death
.

 

An orally bio available broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Timothy P. Sheahan et al.
29 April 2020, in Science
Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Here, we show that the ribonucleoside analog Beta-d-N4 -hydroxycytidine (NHC; EIDD-1931) has broad-spectrum antiviral activity against SARS-CoV-2, MERSCoV, SARS-CoV, and related zoonotic group 2b or 2c bat-CoVs, as well as increased potency against a CoV bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC prodrug (Beta-d-N4 - hydroxycytidine-5′-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral, but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARSCoV-2 and other future zoonotic CoVs.

 

The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study
Qian Liu et al.
29 April 2020, in The Lancet Global Health
Background : In the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in Hubei, China, the local healthcare system was overwhelmed. Physicians and nurses who had no infectious disease expertise were recruited to provide care to patients with COVID-19. To our knowledge, no studies on their experiences of combating COVID-19 have been published. We aimed to describe the experiences of these health-care providers in the early stages of the outbreak.
Methods : We did a qualitative study using an empirical phenomenological approach. Nurses and physicians were recruited from five COVID-19-designated hospitals in Hubei province using purposive and snowball sampling. They participated in semi-structured, in-depth interviews by telephone from Feb 10 to Feb 15, 2020. Interviews were transcribed verbatim and analysed using Haase’s adaptation of Colaizzi’s phenomenological method
.

 

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
Yeming Wang et al.
29 April 2020, in The Lancet
Background : No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.
Methods : We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment.

 

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in COVID-19 Patients
Qing-Lei Zeng et al.
29 April 2020, in The Journal of Infectious Diseases
Currently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) has been reported in almost all countries globally, and no effective therapy has been documented for COVID-19 and the role of convalescent plasma therapy is unknown. In current study, 6 COVID-19 subjects with respiratory failure received convalescent plasma at a median of 21.5 days after first detection of viral shedding, all tested negative for SARS-CoV-2 RNA by 3 days after infusion, and 5 died eventually. In conclusion, convalescent plasma treatment can discontinue SARS-CoV-2 shedding but cannot reduce mortality in critically end-stage COVID-19 patients, and treatment should be initiated earlier.

 

Analysis of mortality in patients of COVID-19: clinical and laboratory parameters
Sufang Tian et al.
29 April 2020, in Open Forum Infectious Diseases
Several reports on epidemiological and clinical features of the 2019 coronavirus disease (COVID-19) had been published. However, mortality and morbidity analysis, important for better understanding of the pathogenesis of this disease, are scarce. We examine the clinical and laboratory features of 14 patients who died of COVID-19. The cohort consisted of 11 male and 3 female patients; nine patients aged 70 years or above, and nearly all had underlying diseases. Fever with bilateral pneumonia was the main manifestation. Most patients had consolidations combined with ground glass opacity (GGO) on chest CT scan. Laboratory tests showed lymphocytopenia in 10 patients, high blood glucose in 11, GGT in 5 of the 14 patients, and high LDH in 5 of 6 patients tested. In addition, patients in this cohort had high level of cytokines such as interleukin 6 in all 8 patients tested. The clinical and laboratory parameters in the cohort of fatal cases may be incorporated into future clinical prognosis models, and will be of help in understanding the pathogenesis of this disease.

 

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases
Andrew W. Byrne et al.
30 April 2020, in medRxiv
Objectives: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by SARS-COV-2 virus, and provide an overview of the variation depending on the methodological approach.
Design: Rapid scoping review. Literature review with fixed search terms, up to 1st April 2020. Central tendency and variation of the parameter estimates for infectious period in (a) asymptomatic (b) symptomatic cases from (i) virological studies (repeated testing), (ii) tracing studies (iii) modelling studies were gathered. Narrative review of viral dynamics.
Information sources: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv, BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was utilised, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, HRB open databases.

 

Genetic structure of SARS-CoV-2 in Western Germany reflects clonal superspreading and multiple independent introduction events
Andreas Walker et al.
30 April 2020, in medRxiv
We whole-genome sequenced 55 SARS-CoV-2 isolates from Western Germany and investigated the genetic structure of SARS-CoV-2 outbreaks in the Heinsberg district and Düsseldorf. While the genetic structure of the Heinsberg outbreak indicates a clonal origin, reflective of superspreading dynamics during the carnival season, distinct viral strains are circulating in Düsseldorf, reflecting the city's international links. Limited detection of Heinsberg strains in the Düsseldorf area despite geographical proximity may reflect efficient containment and contact tracing efforts.

 

Inequalities in COVID19 mortality related to ethnicity and socioeconomic deprivation
Tanith C. Rose et al.
30 April 2020, in medRxiv
Background: Initial reports suggest that ethnic minorities may be experiencing more severe clinical outcomes of coronavirus disease 2019 (COVID19) infections. We therefore assessed the association between ethnic composition, income deprivation and COVID19 mortality rates in England.
Methods: We performed a cross-sectional ecological analysis across upper tier local authorities in England. We assessed the association between the proportion of the population from Black, Asian and Minority Ethnic (BAME) backgrounds, income deprivation and COVID19 mortality rates using negative binomial regression models, whilst adjusting for population density, proportion of the population aged 50–79 and 80+ years, and the duration of the epidemic in each area
.

 

COVID-19 Control Strategies and Intervention Effects in Resource Limited Settings: A Modeling Study
Kiran Raj Pandey et al.
30 April 2020, in medRxiv
Background : Many countries with weaker health systems are struggling to put together a coherent strategy against the COVID-19 epidemic. We explored COVID-19 control strategies that could offer the greatest benefit in resource limited settings.
Methods : Using an age-structured SEIR model, we explored the effects of COVID-19 control interventions--a lockdown, physical distancing measures, and active case finding (testing and isolation, contact tracing and quarantine)-- implemented individually and in combination to control a hypothetical COVID-19 epidemic in Kathmandu (population 2.6 million), Nepal.

 

Increased travel times to United States SARS-CoV-2 testing sites: a spatial modeling study
Benjamin Rader et al.
30 April 2020, in medRxiv
Importance: Access to testing is key to a successful response to the COVID-19 pandemic.
Objective: To determine the geographic accessibility to SARS-CoV-2 testing sites in the United States, as quantified by travel time.
Design: Cross-sectional analysis of SARS-CoV-2 testing sites as of April 7, 2020 in relation to travel time.
Setting: United States COVID-19 pandemic. Participants: The United States, including the 48 contiguous states and the District of Columbia.
Exposures: Population density, percent minority, percent uninsured, and median income by county from the 2018 American Community Survey demographic data.

 

COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids
Michael C. Peters et al.
PMID: 32348692, 29 April 2020, in American Journal of Respiratory and Critical Care Medicine
Background: Coronavirus disease 2019 (COVID-19) is caused by SARS-coronavirus 2 (SARS-CoV-2). Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity.
Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls.

 

Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with disease severity in COVID-19
Yonghong Zhang et al.
PMID: 32348495, 29 April 2020, in Journal of Infectious Diseases
A major unanswered question in the current global COVID-19 outbreak is why a small minority of infected individuals develop severe disease. Here we report that homozygosity for the C allele of rs12252 in the interferon-induced transmembrane protein 3 (IFITM3) gene is associated with more severe disease in an age dependent manner. This supports a role for IFITM3 in disease pathogenesis and the opportunity for early targeted intervention in at risk individuals.

 

Correlation Between Heart Fatty Acid Binding Protein and Severe COVID-19: A Case-Control Study
Li Yin et al.
PMID: 32348339, 29 April 2020, in PloS One
Background: Heart-fatty acid binding protein (HFABP) has been recognized as a highly heart-specific marker. However, it is currently unknown that its HFABP is also closely related to the severity of COVID-19.
Methods: We retrospectively screened 46 patients who met our inclusion criteria within 4 weeks. They were tested for HFABP after the diagnosis of COVID-19, and monitored for HFABP during their hospital stay. We tracked the patients during their hospital stay to determine if they had severe COVID-19 or mild-to-severe transition features. We calculated the chi-square test values found for HFABP to predict the correlation between HFABP levels and the severity of the COVID-19.

 

Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study
Guang Yang et al.
PMID: 32348166, 29 April 2020, in Hypertension
With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACEIs on COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable.

 

29 April, 2020, 14.40 CET

Antibody responses to SARS-CoV-2 in patients with COVID-19
Quan-Xin Long et al.
29 April 2020, in Nature Medicine
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.

 

Population flow drives spatio-temporal distribution of COVID-19 in China
Jayson S. Jia et al.
29 April 2020, in Nature
Sudden, large-scale, and diffuse human migration can amplify localized outbreaks into widespread epidemics.1–4 Rapid and accurate tracking of aggregate population flows may therefore be epidemiologically informative. Here, we use mobile-phone-data-based counts of 11,478,484 people egressing or transiting through the prefecture of Wuhan between 1 January and 24 January 2020 as they moved to 296 prefectures throughout China. First, we document the efficacy of quarantine in ceasing movement. Second, we show that the distribution of population outflow from Wuhan accurately predicts the relative frequency and geographic distribution of COVID-19 infections through February 19, 2020, across all of China. Third, we develop a spatio-temporal “risk source” model that leverages population flow data (which operationalizes risk emanating from epidemic epicenters) to not only forecast confirmed cases, but also to identify high-transmission-risk locales at an early stage. Fourth, we use this risk source model to statistically derive the geographic spread of COVID-19 and the growth pattern based on the population outflow from Wuhan; the model yields a benchmark trend and an index for assessing COVID-19 community transmission risk over time for different locations. This approach can be used by policy-makers in any nation with available data to make rapid and accurate risk assessments and to plan allocation of limited resources ahead of ongoing outbreaks.

 

The trinity of COVID-19: immunity, inflammation and intervention
Matthew Zirui Tay et al.
28 April 2020, in Nature Reviews Immunology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

 

Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients
Yifan Meng et al.
PMID : 32343745, 28 April 2020, in PloS Pathogens
To confirm the relationship between sex and the progression of Coronavirus Disease-19 (COVID-19), and its potential mechanism, among severe patients. For this retrospective study, we included 168 consecutive severe patients with pathogen-confirmed COVID-19 who were hospitalized between January 16th and February 4th, 2020, at Tongji Hospital in Wuhan, China. Clinical characteristics, laboratory parameters, and outcomes were compared and analyzed between males and females. In the present study, we analyzed 168 severe patients with COVID-19, including 86 males and 82 females, and 48 patients (28.6%) were diagnosed as critically ill. Of 86 male patients, 12.8% (11/86) died and 75.6% (65/86) were discharged; of 82 female patients, 7.3% (6/82) died and 86.6% (71/82) were discharged.

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young
Thomas J. Oxley et al.
PMID: 32343504, 28 April 2020, in The New England Journal of Medicine
We report five cases of large-vessel stroke in patients younger than 50 years of age who presented to our health system in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all five patients.

 

Elevated Interleukin-6 and Severe COVID-19: A Meta-Analysis
Muhammad Aziz et al.
PMID:32343429, 28 April 2020, in Journal of Medical Virology
Interleukin-6 is an important marker of inflammation. We performed a systematic review and meta-analysis to demonstrate the association of elevated IL-6 with severe Coronavirus disease-2019 (COVID-19). A total of 9 studies were included in the systematic review and meta-analysis. Patients with severe COVID-19 had a significantly higher serum IL-6 levels compared to non-severe patients (mean difference (MD): 38.6 pg/mL, 95% CI: 24.3 - 52.9 pg/mL, p <0.001, I2 = 98.5%).

 

Long-term Coexistence of SARS-CoV-2 With Antibody Response in COVID-19 Patients
Bin Wang et al.
PMID : 32343415, 28 April 2020, in Journal of Medical Virology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SRAS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days.

 

Neuraxial Anaesthesia and Peripheral Nerve Blocks During the COVID-19 Pandemic: A Literature Review and Practice Recommendations
V. Uppal et al.
PMID : 32344456, 28 April 2020, in Anaesthesia
Coronavirus disease 2019 (COVID-19) has had a significant impact on global healthcare services. In an attempt to limit the spread of infection and to preserve healthcare resources, one commonly used strategy has been to postpone elective surgery, whilst maintaining the provision of anaesthetic care for urgent and emergency surgery. General anaesthesia with airway intervention leads to aerosol generation, which increases the risk of COVID-19 contamination in operating rooms and significantly exposes the healthcare teams to COVID-19 infection during both tracheal intubation and extubation. Therefore, the provision of regional anaesthesia may be key during this pandemic, as it may reduce the need for general anaesthesia and the associated risk from aerosol-generating procedures. However, guidelines on the safe performance of regional anaesthesia in light of the COVID-19 pandemic are limited. The goal of this review is to provide up-to-date, evidence-based recommendations, or expert opinion when evidence is limited, for performing regional anaesthesia procedures in patients with suspected or confirmed COVID-19 infection.

 

Characteristics of Emergency Department Patients With COVID-19 at a Single Site in Northern California: Clinical Observations and Public Health Implications
Youyou Duanmu and al.
PMID : 32344458, 28 April 2020, in Academic Emergency Medicine
The objective of this study was to describe the demographics, clinical characteristics and outcomes of emergency department patients who tested positive for COVID-19 at a medical center in Santa Clara County with the aim of identifying clinical patterns and assessing possible effects of local public health measures. This was an observational, cross-sectional study of emergency department patients with a laboratory confirmed diagnosis of COVID-19 at a single academic hospital (Stanford Health Care). Our emergency department is a tertiary care, level one trauma center which treated approximately 56,000 adults and 23,000 children in 2019.The hospital has 61 intensive care unit (ICU) beds.

Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection
Marissa G. Baker and al.
PMID : 32343747, 28 April 2020, in PloS ONE
Introduction: With the global spread of COVID-19, there is a compelling public health interest in quantifying who is at increased risk of contracting disease. Occupational characteristics, such as interfacing with the public and being in close quarters with other workers, not only put workers at high risk for disease, but also make them a nexus of disease transmission to the community. This can further be exacerbated through presenteeism, the term used to describe the act of coming to work despite being symptomatic for disease. Quantifying the number of workers who are frequently exposed to infection and disease in the workplace, and understanding which occupational groups they represent, can help to prompt public health risk response and management for COVID-19 in the workplace, and subsequent infectious disease outbreaks.
Methods : To estimate the number of United States workers frequently exposed to infection and disease in the workplace, national employment data (by Standard Occupational Classification) maintained by the Bureau of Labor Statistics (BLS) was merged with a BLS O*NET survey measure reporting how frequently workers in each occupation are exposed to infection or disease at work. This allowed us to estimate the number of United States workers, across all occupations, exposed to disease or infection at work more than once a month.

 

Health Insurance Status and Risk Factors for Poor Outcomes With COVID-19 Among U.S. Health Care Workers: A Cross-sectional Study
David U. Himmelstein and Steffie Woolhandler
PMID: 32343764, 28 April 2020, in Annals of Internal Medicine
Background: Li Wenliang, the Chinese physician who raised the first alarm about COVID-19, died of the disease on 7 February. Since then, the pandemic has taken the lives of at least 200 other doctors and nurses (1); lower-paid health care workers filling essential roles may be similarly imperiled.In recent weeks, hospitals in some regions of the United States have been inundated with COVID-19 patients, thousands of nursing home residents have died of the disease, and many infected persons remain at home. Caregivers in these venues are at risk for exposure.
Objective: To assess the number of U.S. health care workers providing direct patient care who have risk factors for a poor outcome if they develop COVID-19 or who lack health insurance or sick leave.
Methods and Findings: We analyzed the most recently available data from 2 in-person surveys of nationally representative samples of the civilian, non-institutionalized U.S. population: the 2018 National Health Interview Survey (n = 72 831) and the March 2019 Current Population Survey (CPS) (n = 180 101).
We generated national estimates (and 95% CIs) by using weights provided in the surveys; the 
surveyfreq procedure in SAS, version 9.4 (SAS Institute); and (for the CPS) replicate weights and the balanced repeated replication method.

 

The Impact of COVID-19 Pandemic on Patients With Chronic Plaque Psoriasis Being Treated With Biologic Therapy: The Northern Italy Experience
P. Gisondi et al.
PMID: 32343839, 28 April 2020, in British Journal of Dermatology
The "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) has spread over the four continents, causing the respiratory manifestations of Coronavirus disease-19 (COVID-19) and satisfying the epidemiological criteria for a pandemic. As of April 1, 2020, more than one million COVID-19 positive cases have been identified and more than 54,000 deaths have occurred worldwide. In Italy, 110,574 positive cases, 49,285 hospitalized patients and 13,155 deaths out of a population of 60,359,546 inhabitants, have been reported, respectively. The highest number of deaths occurred in the northern Italian regions, i.e. Lombardy, Emilia-Romagna, Veneto and Piedmont.

Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19
Di Wu et al.
28 April 2020, in National Science Review
The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients.

 

Role of Drugs Affecting the Renin-Angiotensin-Aldosterone System on Susceptibility and Severity of COVID-19: A Large Case-Control Study from Zheijang Province, China.
Huadong Yan et al.
29 April 2020, in medRxiv
Background. Medical editorials have suggested that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should not be given to people with arterial hypertension during the coronavirus disease 2019 (COVID-19) pandemic because of a potential increased risk of worse clinical outcomes and that calcium channel blockers (CCBs) should be used as an alternative. Methods Using a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China we have tested the role of usage of ACEIs, ARBs, CCBs and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities.

 

Influence of socio-ecological factors on COVID-19 risk: a cross-sectional study based on 178 countries/regions worldwide
Dai Su et al.
29 April 2020, in medRxiv
The initial outbreak of COVID-19 caused by SARS-CoV-2 in China in 2019 has been severely tested in other countries worldwide. We established the Potential Risk Assessment Framework for COVID-19. We used spatial econometrics method to assess the global and local correlation of COVID-19 risk indicators. To estimate the adjusted IRR, we modelled negative binomial regression analysis with spatial information and socio-ecological factors. We found that 37, 29 and 39 countries/regions were strongly opposite from the IR, CMR and DCI index "spatial autocorrelation hypothesis", respectively. The IR, CMR and DCI were significantly associated with some socio-economic factors. We also found that climatic factors (temperature, relative humidity, precipitation and wind speed) did not significantly reduce COVID-19 risk. To fight against COVID-19 more effectively, countries/regions should pay more attention to controlling population flow, improving diagnosis and treatment capacity, and improving public welfare policies.

 

A demographic scaling model for estimating the total number of COVID-19 infections
Christina Bohk-Ewald and al.
29 April 2020, in medRxiv
Background: The total number of COVID-19 infections is critical information for decision makers when assessing the progress of the pandemic, its implications, and policy options. Despite efforts to carefully monitor the COVID-19 pandemic, the reported number of confirmed cases is likely to underestimate the actual number of infections. We aim to estimate the total number of COVID-19 infections in a straightforward manner using a demographic scaling approach based on life tables. Methods: We use data on total number of COVID-19 attributable deaths, population counts, and life tables as well as information on infection fatality rates as reported in Verity et al. (2020) for Hubei, China. We develop a scaling approach based on life tables and remaining life expectancy to map infection fatality rates between two countries to account for differences in their age structure, health status, and the health care system. The scaled infection fatality rates can be used in combination with COVID-19 attributable deaths to calculate estimates of the total number of infected. We also introduce easy to apply formulas to quantify the bias that would be required in death counts and infection fatality rates in order to reproduce a certain estimate of infections.

 

28 April, 2020, 14.30 CET

Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation
Flavio Dormont et al.

27 April 2020, in Science
Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Growing evidence has indicated that uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress. There are currently no effective ways to counter this crosstalk in a targeted manner. Here we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, an endogenous lipid, to adenosine, an endogenous immunomodulator, and then encapsulating α-tocopherol, a natural antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the vascular endothelial barrier dysfunction at sites of acute inflammation, these multidrug nanoparticles could deliver the therapeutic agents in a targeted manner and conferred a significant survival advantage to treated animals in lethal models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel approach for the treatment of acute inflammation with reduced-side effects and high therapeutic potential.

 

Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China:a retrospective cohort study
Qifang Bi et al.
27 April 2020, in The Lancet – Infectious Diseases
Background : Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures.
Methods : From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk.

 

Prevalence of SARS-CoV-2 Infection in Residents of a Large Homeless Shelter in Boston
Travis P. Baggett et al.
27 April 2020, in JAMA
On March 13, 2020, the Boston Health Care for the Homeless Program (BHCHP), in partnership with city and state public health agencies and community partners, rolled out a coronavirus disease 2019 (COVID-19) response strategy that included respiratory symptom screening at shelter front doors, expedited referrals for SARS-CoV-2 testing and isolation for those with respiratory symptoms, dedicated treatment settings for individuals with positive test results, and contact tracing of confirmed COVID-19 cases.Between March 28, 2020, and April 1, 2020, BHCHP identified an increasing number of COVID-19 cases from a single large homeless shelter in Boston, prompting SARS-CoV-2 testing of all remaining shelter residents. We describe the results of this investigation.

 

Exposure to a Surrogate Measure of Contamination From Simulated Patients by Emergency Department Personnel Wearing Personal Protective Equipment
Oren Feldman et al.
27 April 2020, in JAMA
A major challenge with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is the effective protection of health care workers.1 Recommendations for the use of personal protective equipment to protect against SARS-CoV-2 exposure by health care workers were recently published by the World Health Organization and the US Centers for Disease Control and Prevention. For aerosol-generating procedures, N95 respirators, eye protection, isolation gowns, and gloves were recommended. Coveralls, boots with a cover, and hair coverings were not part of the recommended protective clothing. We assessed the protection of emergency physicians and nurses wearing the recommended personal protective equipment while caring for a simulated patient with respiratory distress.

Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals
Yuan Liu et al.

27 April 2020, in Nature
The ongoing COVID-19 outbreak has spread rapidly on a global scale. While the transmission of SARS-CoV-2 via human respiratory droplets and direct contact is clear, the potential for aerosol transmission is poorly understood1–3 . This study investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in diferent areas of two Wuhan hospitals during the COVID-19 outbreak in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients’ toilet areas. Levels of airborne SARS-CoV-2 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. We found that some medical staf areas initially had high concentrations of viral RNA with aerosol size distributions showing peaks in submicrometre and/or supermicrometre regions, but these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted via aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can efectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.

 

The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections
Ilja L. Kruglikov et Philipp E. Scherer
PMID: 32339391, 27 April 2020, in Obesity (Silver Spring)
Coronavirus disease-2019 (COVID-19), caused by the highly pathogenic virus SARS-CoV-2, demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis (PF). In this Perspective, we argue that adipocytes and adipocyte-like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to COVID-19. Expression of angiotensin-converting enzyme 2 (ACE2 - the functional receptor for SARS-CoV) - is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID-19 infections. Similar to the recently established adipocyte-myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF. This may significantly increase the severity of the local response to COVID-19 in the lung. To reduce the severity and mortality with COVID-19, we propose to probe for the clinical response to thiazolidinediones (TZDs), PPARγ agonists, that are the well-known anti-diabetic drugs. TZDs are able to stabilize lipofibroblasts in their "inactive" state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.

 

Vaginal Delivery in SARS-CoV-2 Infected Pregnant Women in Northern Italy: A Retrospective Analysis
Enrico Ferrazzi et al.
PMID: 32339382, 27 April 2020, in BJOG
Objective: To report mode of delivery and immediate neonatal outcome in COVID-19 infected women.
Design: This is a retrospective study.
Setting: Twelve hospitals in northern Italy.
Participants: Pregnant women with COVID-19 confirmed infection who delivered.
Exposure: COVID 19 infection in pregnancy.
Methods: SARS-CoV-2 infected women who were admitted and delivered during the period 1-20 march 2020 were eligible. Data were collected from the clinical records using a standardized questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding

MAIN OUTCOME AND MEASURE: Data on mode of delivery and neonatal outcome RESULTS: 42 women with COVID-19 delivered at the participating centres: 24(57,1%, 95% CI= 41,0-72,3) delivered vaginally. An elective cesarean section was performed in 18/42 (42,9%, 95%CI 27,7-59,0) cases: in 8 cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42(45,2%, 95%CI 29,8-61,3) cases: of these 7/19(36,8%,95CI 16,3-61,6) required oxygen support and 4/19(21,1%,95%CI=6,1-45,6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the post-partum period: their new-borns tested positive for SARS-Cov-2 infection. In one case a new-born had a positive test after a vaginal operative delivery.

 

COVID-19 Associated Pulmonary Aspergillosis
Philipp Koehler et al.
PMID : 32339350, 27 April 2020, in Mycoses
Objectives: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates Coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single center in Cologne, Germany.
Methods: A retrospective chart review of all patients with COVID-19 ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Germany.
Results: COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.

 

ACE2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Endometrial Carcinoma and Renal Papillary Cell Carcinoma: Implication for COVID-19
Jing Yang et al.
PMID : 32339157, 27 April 2020, in Aging
Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and KaplanMeier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages.

 

Early risk factors for the duration of SARS-CoV-2 viral positivity in COVID-19 patients
Aifen Lin et al.
PMID: 32337591, 27 April 2020, in Clinical Infectious Diseases
Background: Pneumonia COVID-19 has became a pandemic. However, information on early risk factors for the duration of SARS-CoV-2 viral positivity is unavailable yet.
Methods: In this prospective study, a cohort of 137 patients with confirmed SARS-CoV-2 infection were enrolled. Clinical information and laboratory data were retrieved from electronic medical records. Viral positivity duration was calculated by an interval from the day SARS-CoV-2 positive confirmed to the day SARS-CoV-2 returned to negative in these 137 COVID-19 patients. Early risk factors for the duration of SARS-CoV-2 viral positivity were evaluated.

 

27 April, 2020, 15.45 CET

Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig
Changhai Lei et al.
24 April 2020, in Nature
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARSCoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2.

 

Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19
Hisashi Kai & Mamiko Kai
27 April 2020, in Hypertension Research
The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.

 

COVID-19 in persons with haematological cancers
Wenjuan He et al.
24 April 2020, in Leukemia
Infection with SARS-CoV-2, the cause of coronavirus infectious disease–19 (COVID-19), has caused a pandemic with >850,000 cases worldwide and increasing. Several studies report outcomes of COVID-19 in predominately well persons. There are also some data on COVID-19 in persons with predominately solid cancer but controversy whether these persons have the same outcomes. We conducted a cohort study at two centres in Wuhan, China, of 128 hospitalised subjects with haematological cancers, 13 (10%) of whom developed COVID-19. We also studied 226 health care providers, 16 of whom developed COVID-19 and 11 of whom were hospitalised. Co-variates were compared with the 115 subjects with haematological cancers without COVID-19 and with 11 hospitalised health care providers with COVID-19. There were no significant differences in baseline co-variates between subjects with haematological cancers developing or not developing COVID-19.

 

Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
Melissa M. Arons et al.
24 April 2020, in The New England Journal of Medicine
Background : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.
Methods :  We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.

 

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. A Randomized Clinical Trial
Mayla G. S. Borba et al.
24 April 2020, in JAMA
Importance : There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.
Objective : To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.
Design, Setting, and Participants :This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon.
Interventions : Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days).

 

Mental Health Status Among Children in Home Confinement During the Coronavirus Disease 2019 Outbreak in Hubei Province, China
Xinyan Xie et al.
24 April 2020, in JAMA Pediatrics
As the coronavirus disease 2019 (COVID-19) epidemic progressed in Wuhan, Hubei province, China, the Chinese government ordered a nationwide school closure. More than 180 million students in China were restricted to their homes (http://www.chinanews.com/sh/2020/02-17/9094648.shtml). The COVID-19 infection has become a global pandemic. As of April 9, 2020, the infection has caused 188 countrywide closures around the world and has affected 1 576 021 818 learners (https://zh.unesco.org/themes/education-emergencies/coronavirus-school-closures). The caution about protecting the mental health of children in home confinement is warranted. This study investigated depressive and anxiety symptoms among students in Hubei province, China, which can help optimize interventions on the mental health of children for stakeholders in all countries affected by COVID-19.

 

Expression of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2in the Gut of Patients With IBD
Juan F. Burgueño et al.
25 April 2020, in Inflammatory Bowel Disease
Background: Patients with inflammatory bowel disease (IBD) have intestinal inflammation and are treated with immune-modulating medications. In the face of the coronavirus disease-19 pandemic, we do not know whether patients with IBD will be more susceptible to infection or disease. We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. We further hypothesized that their expression could be affected by inflammation or medication usage.
Methods: We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. We conducted RNA sequencing for CD11b-enriched cells and peripheral and lamina propria T-cells from well-annotated patient samples.

 

Profile of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Jiuxin Qu et al.
27 April 2020, in Clinical Infectious Diseases
A novel coronavirus (SARS-CoV-2) causing an outbreak of infectious pneumonia (COVID-19) emerged in December 2019 [1, 2]. Because there is currently no specific immunity in the population, humans of all ages and races are susceptible to SARSCoV-2 infection. The World Health Organization (WHO) has declared SARS-CoV-2 a pandemic, and as of Apr 18, 2020, a total of 2,160,207 confirmed COVID-19 cases and 146,088 related deaths had been reported [3]. Diagnosis relies on viral RNA detection by RT-PCR using nasopharyngeal (NP) swabs. Considering the existence of asymptomatic transmission and false negative results of PCR caused by sampling mistakes or sometimes low viral shedding of the NP [4], improvement of COVID-19 diagnostic assays are still needed. Similar to SARS-CoV and MERS-CoV, the understanding of antibody responses specific to SARS-CoV-2 in patients will be helpful for diagnosis, seroepidemiologic surveys, and pathogenesis studies. In this study, we investigated the humoral immunity of hospitalized patients, analyzed the profile of IgG and IgM antibodies against the SARS-CoV-2 in 41 COVID-19 patients between three and 43 days of their illness.

 

First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) in a pediatric dialysis unit
Vera Schwierzeck et al.
27 April 2020, in Clinical Infectious Diseases
Background: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM).
Methods: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases
.

 

The Impact of Respiratory Protective Equipment on Difficult Airway Management: A Randomised, Crossover, Simulation Study
J. Schumacher et al.
PMID: 32335900, 26 April 2020, in Anaesthesia
This study compares the impacts of standard air purifying respirators and powered air purifying respirators during simulated difficult airway scenarios. Twenty-five anaesthetists carried out four different standardised difficult intubation drills, either unprotected (control), or wearing a standard, or a powered respirator. Treatment times and wearer comfort were determined and compared. In the wearer comfort evaluation form, operators rated mobility, noise, heat, vision, and speech intelligibility. All anaesthetists accomplished the treatment objectives of all study arms without adverse events.

 

Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by Versus People Unaffected by Quarantine During the COVID-19 Epidemic in Southwestern China
Lei Lei et al.
PMID: 32335579, 26 April 2020, Medical Science Monitor
Background : At the end of 2019, the COVID-19 outbreak began in Wuhan, Hubei, China, and spread rapidly to the whole country within 1 month. This new epidemic caused a great mental reaction among the public. This study aimed to assess and compare the prevalence and associated factors of anxiety and depression among the public affected by quarantine and those unaffected during the COVID-19 outbreak in southwestern China in early Feb. 2020.
Material and Methods: Data were collected using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) administered to 1593 respondents aged 18 years and above. The respondents were grouped as ‘affected group’ and ‘unaffected group’ on the basis of whether they or their families/colleagues/classmates/neighbors had been quarantined.

 

Transmission risk of SARS-CoV-2 to healthcare workers – observational results of a primary care hospital contact tracing
Vera Canova et al.
PMID: 32333603, 25 April 2020, in Swiss Medical Weekly
Background: The coronavirus disease (COVID)-19 epidemic is evolving rapidly. Healthcare workers are at increased risk for infection, and specific requirements for their protection are advisable to ensure the functioning of the basic healthcare system, including the availability of general practitioners (GPs). Understanding the transmission risk is particularly important for guiding evidence-based protective measures in the primary healthcare setting.
Methods: Healthcare worker contacts of an initially undiagnosed COVID-19 case, who were without personal protective equipment, in particular not wearing facemasks, were screened with nasopharyngeal swabs and polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), irrespective of respiratory symptoms or fever seven days after initial contact. The details of exposure to the index case were obtained during routine contact investigation after unintentional pathogen exposure.

 

Evaluation of Ocular Symptoms and Tropism of SARS-CoV-2 in Patients Confirmed With COVID-19
Nan Hong et al.
PMID: 32336042, 26 April 2020, in Acta Ophtalmologica
Purpose: The SARS-CoV-2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS-CoV-2 in a group of patients with COVID-19.
Method: Fifty-six patients infected with SARS-CoV-2 were recruited as subjects. Relevant medical histories were obtained from the electronic medical record system. Ocular history and ocular symptoms data were obtained by communicating directly with the subjects. The Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ) were used to assess the anterior ocular surface condition before and after the onset of disease.

 

Modeling geographical spread of COVID-19 in India using network-based approach
Ankush Kumar
27 April 2020, in medRxiv
COVID-19 pandemic is a global concern, due to its high spreading and alarming fatality rate. Mathematical models can play a decisive role in mitigating the spread and predicting the growth of the epidemic. India is a large country, with a highly variable inter-state mobility, and dynamically varying infection cases in different locations; thus, the existing models, based solely on the aspects of growth rates, or generalized network concepts, may not provide desired predictions. The internal mobility of a country must be considered, for accurate prediction. Herein, we propose a framework for predicting the geographical spread of COVID-19, using reported COVID-19 cases, census migration data, and monthly airline data of passengers. We discover that spreading depends on the spatial distribution of existing cases, human mobility patterns, and administrative decisions. In India, the mobility towards professional sites can surge incoming cases at Maharastra and Karnataka, while migration towards the native places can risk Uttar Pradesh and Bihar. We anticipate that the state Kerala, with one of the highest cases of COVID-19, may not receive significant incoming cases, while Karnataka and Haryana may receive the challenge of high incoming cases, with medium cases so far. Using airline passenger's data, we also estimate the number of potential incoming cases at various airports. The study predicts that the airports located in the region of north India are vulnerable, whereas in northeast India and in some south India are relatively safe. The detailed analysis in this direction will guide policymakers for prior planning of transport, and minimize the spread of COVID-19.

 

Association between environmental pollution and prevalence of coronavirus disease 2019 (COVID-19) in Italy
Giuseppe Lippi et al.
27 April 2020, in medRxiv
The novel coronavirus disease 2019 (COVID-19) has recently been upgraded to a pandemic by the World Health Organization due to the alarming levels of spread and severity. Since several lines of evidence also attest that Lombardy region has an extraordinarily high level of environmental pollution, we aimed to explore the potential epidemiological association between the number of cases of COVID-19 and environmental pollution in Italy. Data on environmental pollution in Italy were retrieved from the 2019 annual report of the organization Legambiente (League for the Ambient). The adjusted correlation between the number of days in which environmental pollutants exceeded established limits and the overall number of COVID-19 cases reveals the existence of a highly significant positive association (r=0.66; 95% CI, 0.48-0.79; p<0.001). The association remained statistically significant even when the number of days above pollutant limits was correlated with the number of COVID-19 cases per 1000 inhabitants (r=0.43; 95% CI, 0.18-0.62; p=0.001). Living in a province with over 100 days per year in which environmental pollutants were exceeded was found to be associated with a nearly 3-fold higher risk of being positive for COVID-19 (0.014 vs. 0.005 COVID-19 cases per 1000 inhabitants; OR, 2.96; 95% 2.12-4.13; p<0.001). Reinforced restrictive measures shall be considered in areas with higher air pollution, where the virus is more likely to find a fertile biological or environmental setting.

 

24 April,2020, 14.00 CET

Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States
The COVID-19 Investigation Team
23 April 2020, in Nature Medicine
Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously1–3 . Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21–68); 8 patients were male. Common symptoms at illness onset were cough (n= 8) and fever (n= 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
Waradon Sungnak et al.
23 April 2020, in Nature Medicine
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.

Translating IL-6 biology into effective treatments 
Ernest H. Choy et al.
23 April 2020, in Nature Reviews Rheumatology
In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, giant cell arteritis and Takayasu arteritis, as well as other conditions such as Castleman disease and cytokine release syndrome. Targeting this pathway has also identified avenues for potential expansion into several other indications, such as uveitis, neuromyelitis optica and, most recently, COVID-19 pneumonia. To mark the tenth anniversary of anti-IL-6 receptor therapy worldwide, we discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signalling, including the successes and challenges and with an emphasis on rheumatic diseases.

Renin–Angiotensin–Aldosterone SystemInhibitors in Patients with Covid-19
Muthiah Vaduganathan et al.
23 April 2020, in The New England Journal of Medicine
Given the common use of ACE inhibitors and ARBs worldwide, guidance on the use of these drugs in patients with Covid-19 is urgently needed. Here, we highlight that the data in humans are too limited to support or refute these hypotheses and concerns. Specifically, we discuss the uncertain effects of RAAS blockers on ACE2 levels and activity in humans, and we propose an alternative hypothesis that ACE2 may be beneficial rather than harmful in patients with lung injury. We also explicitly raise the concern that withdrawal of RAAS inhibitors may be harmful in certain high-risk patients with known or suspected Covid-19.

The effect of travel restrictions on the spread of the 2019 novel coronavirus (COVID-19) outbreak
Matteo Chinazzi et al.
24 April 2020, in Science
Motivated by the rapid spread of coronavirus disease 2019 (COVID-19) in mainland China, we use a global metapopulation disease transmission model to project the impact of travel limitations on the national and international spread of the epidemic. The model is calibrated on the basis of internationally reported cases and shows that, at the start of the travel ban from Wuhan on 23 January 2020, most Chinese cities had already received many infected travelers. The travel quarantine of Wuhan delayed the overall epidemic progression by only 3 to 5 days in mainland China but had a more marked effect on the international scale, where case importations were reduced by nearly 80% until mid-February. Modeling results also indicate that sustained 90% travel restrictions to and from mainland China only modestly affect the epidemic trajectory unless combined with a 50% or higher reduction of transmission in the community.

Epidemiological Assessment of Imported Coronavirus Disease 2019 (COVID-19) Cases in the Most Affected City Outside of Hubei Province, Wenzhou, China
Yi Han et al.
23 April 2020, in JAMA
The coronavirus disease 2019 (COVID-19) outbreak was first identified in Wuhan, the capital of Hubei Province, China, in December 2019.1 The disease spread rapidly from Wuhan to other cities. To contain this epidemic, Wuhan was locked down on January 23, 2020. Wenzhou, which has a population of 9.3 million and is located in southeastern China approximately 600 miles from Wuhan, is the most affected Chinese city outside of Hubei. Approximately 48 800 people traveled from Wuhan to Wenzhou from January 10 to 23, 2020. As of February 15, 2020, there were 502 confirmed cases of COVID-19 but no deaths reported in Wenzhou. To stop the spread of COVID-19 in Wenzhou, multiple community containment approaches were implemented beginning January 24, 2020, including quarantine, isolation, traffic control, and social distancing. This decision analytical model examined several key epidemiological features of imported COVID-19 cases in Wenzhou.

SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airwayepithelial cells and is detected in specific cell subsets across tissues
Carly G. K. Ziegler et al.
In Cell
There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discover that ACE2 is a human interferonstimulated gene (ISG) in vitro using airway epithelial cells, and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.

Incidence of Adverse Drug Reactions in COVID-19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System
Ji Sun et al.
PMID: 32324898, 23 April 2020, in Clinical Pharmacology & Therapeutics
To evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among COVID-19 patients by Hospital Pharmacovigilance System (CHPS). A retrospective analysis was performed on 217 COVID-19 patients admitted to the First Hospital of Changsha in China, from January 17, 2020 to February 29, 2020. The active monitoring model in CHPS was used to detect ADR signals of hospital information system. The risk factors for the ADRs were classified using the WHO-UMC system. Univariate and multivariate logistic regression was carried out to analyze the risk factors of ADRs. Our results showed that the prevalence of ADRs was 37.8% in the patients, which was predominated by drug-induced gastrointestinal disorders and liver system disorders (23.0% vs. 13.8% ).

Does High Cardiorespiratory Fitness Confer Some Protection Against Pro-Inflammatory Responses After Infection by SARS-CoV-2?
Hermann Zbinden-Foncea et al.
PMID: 32324968, 23 April 2020, in Obesity (Silver Spring)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symtoms of SARS-CoV-2 and the subsequent prognosis is worsened in individuals who have pre-exisiting comorbidities prior to infection by the virus. Individuals with obesity/overweight, insulin resistance and diabetes typically have chronic low-grade inflammation characterized by increased levels of several pro-inflammatory cytokines and the inflammasome: this state predisposes to greater risk for infection along with more adverse outcomes. Here we consider whether a high level of cardiorespiratory fitness induced by prior exercise training may confer some innate immune-protection against Covid-19 by attenuating the "cytokine storm syndrome" often experienced by "at risk" individuals.

Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?
Ahmed S. Abouhashem et al.
PMID: 32323565, 23 April 2020, in Antioxidants & Redox Signaling
Human lungs single cell RNA sequencing data from healthy donors (elderly and young; GEO accession number GSE122960) were analyzed to isolate and specifically study gene expression in alveolar type II cells. Co-localization of ACE2 and TMPRSS2 enables SARS-CoV 2 to enter the cells. Expression of these genes in the alveolar type II cells of elderly and young patients were comparable and therefore do not seem to be responsible for worse outcomes observed in COVID-19 affected elderly. In cells from the elderly, 263 genes were downregulated and 95 upregulated. SOD3 was identified as the top-ranked gene that was most down-regulated in the elderly. Other redox-active genes that were also downregulated in cells from the elderly included ATF4 and M2TA. ATF4, an ER stress sensor that defends lungs via induction of heme oxygenase 1. The study of downstream factors known to be induced by ATF4, according to Ingenuity Pathway AnalysisTM, identified 24 candidates. Twenty-one of these were significantly downregulated in the cells from the elderly. These downregulated candidates were subjected to enrichment using the Reactome Database identifying that in the elderly, the ability to respond to heme deficiency and the ATF4-dependent ability to respond to endoplasmic reticulum stress is significantly compromised. SOD3-based therapeutic strategies have provided beneficial results in treating lung disorders including fibrosis. The findings of this work propose the hypotheses that lung-specific delivery of SOD3/ATF4 related antioxidants may work in synergy with promising anti-viral drugs such as remdesivir to further improve COVID-19 outcomes in the elderly.

Rapid and Sensitive Detection of anti-SARS-CoV-2 IgG Using Lanthanide-Doped Nanoparticles-Based Lateral Flow Immunoassay 
Zhenhua Chen et al.
PMID: 32323974, 23 April 2020, in Analytical Chemistry
The outbreak of 2019 coronavirus disease (COVID-19) has been a challenge for hospital laboratories because of the huge number of samples that must be tested for the presence of the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simple and rapid immunodiagnostic methods are urgently needed to identify positive cases. Here we report the development of a rapid and sensitive lateral flow immunoassay (LFIA) that uses lanthanide-doped polysterene nanoparticles (LNPs) to detect anti-SARV-CoV-2 IgG in human serum. A recombinant nucleocapsid phosphoprotein of SARS-CoV-2 was dispensed onto a nitrocellulose membrane to capture specific IgG. Mouse anti-human IgG antibody was labeled with self-assembled LNPs that served as a fluorescent reporter. A 100-μl aliquot of serum samples (1:1000 dilution) was used for this assay and the whole detection process took 10 min. The results of the validation experiment met the requirements for clinical diagnostic reagents. A value of 0.0666 was defined as the cutoff value by assaying 51 normal samples. We tested 7 samples that were positive by reverse-transcription (RT-)PCR and 12 that were negative but clinically suspicious for the presence of anti-SARS-CoV-2 IgG. One of the negative samples was determined to be SARS-CoV-2 IgG positive, while the results for the other samples were consistent with those obtained by RT-PCR. Thus, this assay can achieve rapid and sensitive detection of anti-SARS-CoV-2 IgG in human serum and allow positive identification in suspicious cases; it can also be useful for monitoring the progression COVID-19 and evaluating patients' response to treatment.

Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China
Juyi Li et al.
PMID: 32324209, 23 April 2020, in JAMA Cardiology
Importance: Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19).
Objective: To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection.
Design, setting, and participants: Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020.
Main outcomes and measures: COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs non-severe illness and between survivors vs non-survivors.

COVID-19 Infection and Treatment With Hydroxychloroquine Cause Severe Haemolysis Crisis in a Patient With glucose-6-phosphate Dehydrogenase Deficiency
Yan Beauverd et al.
PMID: 32324284, 23 April 2020, in European Journal of Haematology
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited genetic disorder caused by red cell enzymatic defects and is associated with haemolytic crisis when patients are exposed to oxidative agents (fava beans, drugs, infections). Hydroxychloroquine is suspected to trigger haemolytic crisis in G6PD deficient patients, and off-label administration of this drug to patients infected with the novel coronavirus (SARS-CoV-2) could cause concern. We report here the first case of severe haemolytic crisis in a patient with G6PD deficiency, initiated by severe COVID-19 infection and hydroxychloroquine use. With worldwide spread of COVID-19, especially in regions with a high prevalence of G6PD deficiency, our case should alert physicians to this possible correlation.

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19
Jian-Dong Huang et al.
24 April 2020, in bioRxiv
In this study, we mapped the immunodominant (ID) sites of S protein using sera samples collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-specific antibody levels in the sera of recovered COVID-19 patients were strongly correlated with the neutralising antibody titres. We used epitope mapping to determine the landscape of ID sites of S protein, which identified nine linearized B cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-CoV-2 antibody binding sites. Peptides containing two out of the nine sites were tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised mice. This study for the first time provides human serological data for the design of vaccines against COVID-19.

SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors.
Ludivine Grzelak et al.
24 April 2020, in medRxiv
It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre- epidemic individuals, 51 patients from Hopital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C- terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV- 2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.

Higher mortality in men from COVID19 infection-understanding the factors that drive the differences between the biological sexes.
Swaminathan P. Iyer et al.
24 April 2020, in medRxiv
The emergent global pandemic caused by the rapid spread of Severe Acute Respiratory syndrome- Coronavirus-2 (SARS-CoV-2) has led to increased mortality and negatively impacted day to day activities of humankind within a short period of time. As the data is rapidly emerging from earlier outbreak locations around the world, there are efforts to assimilate this with the knowledge from prior epidemics and find rapid solutions for this. One of the observations and a recurring theme is the disproportionate differences in the incidence of infection and the consequent mortality between males and females. We, therefore, analyzed retrospective datasets from the previous epidemics and the ongoing pandemic in order to address these differences in clinical outcomes. The data shows that even though the infection rates are similar, the odds ratio of male mortality remains high, indicating a divergence in the crosstalk between the three pathogenic human Coronavirus (hCoVs)- the SARS-CoV, MERS-CoV and the SARS-CoV-2 and immune effectors in the two sexes. One proximate cause is the sex-specific modulation of the X-linked genes that can influence susceptibility to infection. Future studies are needed to confirm these findings, which can form the basis for developing rational strategies for ending the current and preventing future pandemics.

STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters
Robbert Boudewijns et al.
24 April 2020, in bioRxiv
Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and prospected hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS-CoV-2. In wild-type hamsters, SARS-CoV-2 infection triggers bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. We further assess SARS-CoV-2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Finally, we identify an exuberant innate response as key player in immune pathogenesis, in which STAT2 signaling plays a double-edged role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results endorse hamsters as pre-clinical model to rationalize and assess the therapeutic benefit of new antivirals or immune modulators for the treatment of COVID-19 patients.

 


 

23 April, 2020, 13.00 CET

Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy
Giulia Giordano et al.
22 April 2020, in Nature Medicine
In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.

Prevalence of malnutrition and analysis of related factors in elderly patients with COVID-19 in Wuhan, China
Tao Li et al.
22 April 2020, in European Journal of Clinical Nutrition
Background/objectives To evaluate the prevalence of malnutrition and its related factors in elderly patients with COVID-19 in Wuhan, China. Subjects/methods In a cross-sectional study, we evaluated the nutritional status of elderly inpatients with COVID-19 using the Mini Nutritional Assessment (MNA). Based on MNA scores, patients were divided into non-malnutrition group (MNA ≥ 24), the group with risk of malnutrition (MNA 17–23.5) and malnutrition group (MNA score < 17). Regression analysis was conducted to screen for risk factors for malnutrition.

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
Safiya Richardson et al.
22 April 2020, in JAMA
Importance :There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
Objective :To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system.
Design, Setting, and Participants :Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.

 

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents
Riccardo Castagnoli et al.
22 April 2020, in JAMA Pediatrics
Importance :The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive strategies and optimal medical management. While data are available for adult patients with coronavirus disease 2019 (COVID-19), limited reports have analyzed pediatric patients infected with SARS-CoV-2.
Objective :To evaluate currently reported pediatric cases of SARS-CoV-2 infection.
Evidence Review : An extensive search strategy was designed to retrieve all articles published from December 1, 2019, to March 3, 2020, by combining the terms coronavirus and coronavirus infection in several electronic databases (PubMed, Cochrane Library, and CINAHL), and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Retrospective cross-sectional and case-control studies, case series and case reports, bulletins, and national reports about the pediatric SARS-CoV-2 infection were included. The risk of bias for eligible observational studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

 

Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection
Giacomo Spinato et al.
22 April 2020, in JAMA
Despite anecdotal reports of anosmia, only 1 study to our knowledge has evaluated the prevalence of smell and taste disturbance in hospitalized patients with COVID-19, reporting an overall prevalence of 34% but without data on timing of onset in relation to other symptoms. This study evaluated prevalence, intensity, and timing of an altered sense of smell or taste in patients with SARS-CoV-2 infections.

 

Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers
Yanfeng Pan et al.
22 April 2020, in The Journal of Infectious Diseases
Background: We retrospectively analysed 26 persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carriers.
Methods: Epidemiological and clinical characteristics from the 26 asymptomatic patients with positive results for SARS-CoV-2 RNA testing were obtained.

 

Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
Wenhao Dai et al.
22 April 2020, in Science
SARS-CoV-2 is the etiological agent responsible for the global COVID-19 outbreak. The main protease (Mpro) of SARS-CoV-2 is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at 1.5 Å resolution, showed that the aldehyde groups of 11a and 11b are covalently bound to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity, suggesting that these compounds are promising drug candidates.

 

High Incidence of Venous Thromboembolic Events in Anticoagulated Severe COVID-19 Patients
Jean-François Llitjos et al.
PMID: 32320517, in Journal of Thrombosis and Haemostasis
Background: Coagulopathy is a common abnormality in patients with COVID-19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated severe COVID-19 patients.
Objectives: Systematic assessment of VTE using complete duplex ultrasound (CDU) in anticoagulated COVID-19 patients.
Patients and methods: We performed a retrospective study in 2 French intensive care units (ICU) were CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID-19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.

 

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Potential, Iran, 2020
Kamalich Muniz-Rodriguez
PMID: 32320641, 22 April 2020, in Emerging Infectious Diseases
To determine the transmission potential of severe acute respiratory syndrome coronavirus 2 in Iran in 2020, we estimated the reproduction number as 4.4 (95% CI 3.9–4.9) by using a generalized growth model and 3.5 (95% CI 1.3–8.1) by using epidemic doubling time. The reproduction number decreased to 1.55 after social distancing interventions were implemented.

 

Scientific Research Progress of COVID-19/ SARS-CoV-2 in the First Five Months
Hua Li et al.
PMID: 32320516, 22 April 2020, in Journal of Cellular and Molecular Medicine
A cluster of pneumonia (COVID-19) cases have been found in Wuhan China in late December, 2019 and subsequently a novel coronavirus with a positive stranded RNA was identified to be the etiological virus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), which has a phylogenetic similarity to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV-2 transmits mainly through droplets and close contact and the elder or people with chronic diseases are high-risk population. People affected by SARS-CoV-2 can be asymptomatic, which brings about more difficulties to control the transmission. COVID-19 has become pandemic rapidly after onset and so far the infected people have been above 2,000,000 and more than 130,000 died worldwide according to COVID-19 situation dashboard of World Health Organization (https://covid19.who.int). Here, we summarized the current known knowledge regarding epidemiological, pathogenesis, pathology, clinical features, comorbidities and treatment of COVID-19/ SARS-CoV-2 as reference for the prevention and control COVID-19.

 

The Prevalence, Characteristics and Prevention Status of Skin Injury Caused by Personal Protective Equipment Among Medical Staff in Fighting COVID-19: A Multi-Center, Cross-Sectional Study
Qixia Jiang et al.
PMID: 32320359, 22 April 2020, in Advances in Wound Care
OBJECTIVE: To investigate the prevalence, characteristics and preventive status of skin injuries caused by personal protective equipment (PPE) in medical staff.
APPROACH: A cross-sectional survey was conducted online for understanding skin injuries among medical staff fighting against COVID-19 in February 8-22, 2020. Participants voluntarily answered and submitted the questionnaire with cellphone. The questionnaire items included demographic data, grade of PPE and daily wearing time, skin injuries types, anatomical sites, and preventive measures. Univariable analyses and logistic regression analyses were employed to explore the risk factors associated with skin injuries. 

 

Anti-SARS-CoV-2 Virus Antibody Levels in Convalescent Plasma of Six Donors Who Have Recovered From COVID-19
Libo Zhang et al.
PMID: 32320384, 22 April 2020, in Aging
Background: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported.
Methods: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.

 

Evaluation of the Auxiliary Diagnostic Value of Antibody Assays for the Detection of Novel Coronavirus (SARS-CoV-2)
Gao Yong et al.
PMID: 32320064, 22 April 2020, in Journal of Medical Virology
The spread of SARS-CoV-2 has taken on pandemic proportions, affecting over 100 countries in a matter of weeks. The goal of this study was to assess the diagnostic values of different methods of detecting and estimating the SARS-CoV-2 infection, and the auxiliary diagnostic potential of antibody assays. By retrospectively analyzing the data of viral RNAs and serum IgM-IgG antibodies against SARS-CoV-2 from 38 cases with confirmed COVID-19 in the Second People's Hospital of Fuyang, we found that, in the early phase of the illness, the viral RNA was most abundant in the sputum specimens, followed by that in the throat swabs, while the antibody assays identified fewer positive cases at this stage. However, the sensitivity of the antibody assays overtook that of RNA test from eighth day of disease onset. Simultaneous use of antibody assay and RT-qPCR improved the sensitivity of the diagnoses. Moreover, we found that most of these cases with no detectable viral RNA load during the early stages were able to be seropositive after 7 days. Our findings indicate that the antibody detection could be used as an effective supplementary indicator of SARS-CoV-2 infection in suspected cases with no detectable viral RNA, and in conjunction with nucleic acid detection in confirming the infection.

 

Successful Containment of COVID-19 Outbreak in a Large Maternity and Perinatal Center While Continuing Clinical Service
Michael Kabesch et al.
PMID : 32319131, 22 April 2020, in Pediatric Allergy and Immunology
With increasing numbers of SARS-CoV-2 infections and COVID-19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20 % of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3,000 births per year, an outbreak of COVID-19 occurred in March 2020, affecting 36 staff members, including doctors, nurses and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS-CoV-2. Apart from massive testing of personnel in predefined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak.

 

Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time
Jaime Berumen et al.
23 April 2020, in medRxiv
Objective: To analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them (ΔDD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone.
Design: Retrospective incident case study.
Setting: WHO based register of cumulative incidence of Covid-19 cases.
Participants: 1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020.
Exposures : SARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical)
Main outcome measures :. Comparison of DCS, D100, ΔDD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models.

 

The anticoagulant nafamostat potently inhibits SARS-CoV-2 infection in vitro: an existing drug with multiple possible therapeutic effects
Mizuki Yamamoto
23 April 2020, in bioRxiv
Although infection by SARS-CoV-2, the causative agent of COVID-19, is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked MERS-CoV S protein-initiated cell fusion by targeting TMPRSS2, and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on SARS-CoV-2 S protein, ACE2 and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an EC50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. These findings, together with accumulated clinical data regarding its safety, make nafamostat a likely candidate drug to treat COVID-19.

 

22 April, 2020, 16.20 CET

Connecting clusters of COVID-19: an epidemiological and serological investigation
Sarah Ee Fang Yang et al.
21 April 2020, in The Lancet – Infectious Diseases
Background : Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19.
Methods :In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection.

 

Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study
Hin Chu et al.
21 April 2020, in The Lancet – Microbe
Background : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported from China in January, 2020. SARS-CoV-2 is efficiently transmitted from person to person and, in 2 months, has caused more than 82000 laboratoryconfirmed cases of coronavirus disease 2019 (COVID-19) and 2800 deaths in 46 countries. The total number of cases and deaths has surpassed that of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV). Although both COVID-19 and severe acute respiratory syndrome (SARS) manifest as pneumonia, COVID-19 is associated with apparently more efficient transmission, fewer cases of diarrhoea, increased mental confusion, and a lower crude fatality rate. However, the underlying virus–host interactive characteristics conferring these observations on transmissibility and clinical manifestations of COVID-19 remain unknown.
Methods : We systematically investigated the cellular susceptibility, species tropism, replication kinetics, and cell damage of SARS-CoV-2 and compared findings with those for SARS-CoV. We compared SARS-CoV-2 and SARS-CoV replication in different cell lines with one-way ANOVA. For the area under the curve comparison between SARS-CoV-2 and SARS-CoV replication in Calu3 (pulmonary) and Caco2 (intestinal) cells, we used Student’s t test. We analysed cell damage induced by SARS-CoV-2 and SARS-CoV with one-way ANOVA.

 

Effect of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China: a modelling study
Tim K. Tsang et al.
21 April 2020, in The Lancet – Public Health
Background: When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China.
Methods: We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic.

 

Fever without a source in a young infant due to SARS-CoV-2
Matthew J. Kan et al.
22 April 2020, in Journal of the Pediatric Infectious Diseases Society
A 5-week-old infant admitted for fever without a source subsequently tested positive for SARS-CoV-2. She had a mild hospital course without respiratory distress. This unexpected presentation changed regional hospital screening for COVID-19 and personal protective equipment use by medical providers evaluating infants with fever without a source.

 

Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China
Xiao-Lin Jiang et al.
22 April 2020, in The Journal of Infectious Diseases
Data concerning the transmission of SARS-CoV-2 in asymptomatic and paucisymptomatic patients are lacking. We report a three-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight (53%) of 15 members from three families were confirmed with SARS-CoV-2 infection. Of eight patients, three were asymptomatic and one was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household. The complete genomes of SARS-CoV-2 from the patients were >99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

 

What’s New With the Old Coronaviruses?
Chikara Ogimi et al.
21 April 2020, in  Journal of the Pediatric Infectious Diseases Society
Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the “common cold.” Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.

Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
Shufa Zheng et al.
21 April 2020, in The BMJ
Objective : To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) during the first four months of the epidemic in Zhejiang province, China.
Design : Retrospective cohort study.
Setting : A designated hospital for patients with covid-19 in Zhejiang province, China.
Participants : 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease.
Data were collected from 19 January 2020 to 20 March 2020.

Rapid detection of COVID-19 coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform
Lin Yu et al.
21 April 2020, in Clinical Chemistry
The recent outbreak of a novel coronavirus SARS-CoV-2 (also known as 2019-nCoV) threatens global health, given serious cause for concern. It is urgent to develop rapid, accurate and onsite diagnosis methods in order to effectively identify these early infects, treat them on time and control the disease spreading. For RNA virus infections, especially acute respiratory infection, probe coupled RT-qPCR from respiratory secretions is routinely used to detect causative viruses. However, RT-qPCR has many limitations such as the need for high purity samples, trained personnel and sophisticated facilities for sample processing and the access to expensive laboratory instruments, as well as requiring long reaction times (around 2 hs). Loopmediated isothermal amplification (LAMP) combined with reverse transcription (RT-LAMP), allows the direct detection of RNA. This system, can be coupled with a pH indicator present in the reaction mix allowing readout of the amplification reaction by change in color.
Here we describe a LAMP based method named iLACO (isothermal LAMP based method for COVID-19) for rapid detection of the SARS-CoV-2. We selected a fragment of the ORF1ab as target region and used the online software Primer Explorer V5 (http://primerexplorer.jp/lampv5e/index.html) to design the RT-LAMP primers. We ensured the primer specificity by comparing the target sequence with other viral genomes, including nine corona and two influenza viruses using the NCBI BLAST tool.

 

COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure
Luca Spiezia et al.
PMID: 32316063, 21 April 2020, in Thrombosis and Haemostasis
In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls (p < 0.0001 in both comparisons). Interestingly enough, markedly hypercoagulable thromboelastometry profiles were observed in COVID-19 patients, as reflected by shorter Clot Formation Time (CFT) in INTEM (p = 0.0002) and EXTEM (p = 0.01) and higher Maximum Clot Firmness (MCF) in INTEM, EXTEM and FIBTEM (p < 0.001 in all comparisons). In conclusion, COVID-19 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.

 

Clinical and Autoimmune Characteristics of Severe and Critical Cases With COVID-19
Yaqing Zhou et al.
PMID: 32315487, 21 April 2020, in Clinical and Translational Science
We aimed to report the clinical and autoimmune characteristics of severe and critical novel coronavirus pneumonia caused by SARS-CoV-2. The clinical, autoimmune, and laboratory characteristics of 21 patients who had laboratory-confirmed severe and critical cases of COVID-19 from the intensive care unit (ICU) ward of the Huangshi Central Hospital, Hubei Province, China were investigated. A total of 21 patients (13 males and eight females) including eight (38.1%) severe cases and 13 (61.9%) critical cases were enrolled. Cough (90.5%) and fever (81.0%) were the dominant symptoms, and most of them (76.2%) had at least one coexisting disorder on admission. The most common characteristics on chest CT were ground-glass opacity (100%) and bilateral patchy shadowing (76.2%). The most common findings on laboratory measurements were lymphocytopenia (85.7%), elevated levels of C-reactive protein (94.7%), and Interleukin-6 (89.5%). The prevalence of anti-52 kDa SSA/Ro antibody, anti-60 kDa SSA/Ro antibody and antinuclear antibody in the cases was 20%, 25% and 50% respectively. In the present work, we retrospectively analyzed the clinical and laboratory data from 21 severe and critical cases with COVID-19. Autoimmune phenomena exist in COVID-19 subjects, and the results provide the rationale for a strategy of prevention of dysfunction of immune and optimal immunosuppressive therapy in the future.

Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2)
Alberto Paniz-Mondolfi et al.
PMID: 32314810, 21 April 2020, in Journal of Medical Virology
Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with Severe Acute Respiratory Syndrome Coronavirus-2. Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement.

 

Understanding Evolution of SARS-CoV-2: A Perspective From Analysis of Genetic Diversity of RdRp Gene
Sunitha M. Kasibhatla et al.
PMID: 32314811, 21 April 2020, in Journal of Medical Virology
Background & objectives: COVID-19 emerged as the first example of "Disease X", a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as SARS-CoV-2. The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RdRp gene, a stable genetic marker.
Methods: Phylogenetic and population stratification analyses were carried out using Maximum likelihood and Bayesian methods, respectively.

Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation and Cytokine Amplification in COVID-19
Paul MacDaragh Ryan et Noel M. Caplice
PMID : 32314868, 21 April 2020, in Obesity (Silver Spring)
Coronavirus disease 2019 (COVID-19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcome include advanced age, male gender, pre-existing cardiovascular disease and risk factors including hypertension, diabetes and more recently obesity. Herein, we posit new obesity-driven predictors of poor COVID-19 outcome, over and above the more obvious extant risks associated with obesity including cardiometabolic disease and hypoventilation syndrome in intensive care patients. We outline a theoretical mechanistic framework whereby adipose tissue in subjects with obesity may act as a reservoir for more extensive viral spread with increased shedding, immune activation and cytokine amplification. We propose studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in subjects with obesity and COVID-19. Finally, we underscore emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.

 

21 April, 2020, 17.00 CET

Experiences of Patients With Rheumatic Diseases in the US During Early Days of the COVID-19 Pandemic
Kaleb Michaud et al.
PMID: 32311836, 20 April 2020, in ACR Open Rheumatology
Objective: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID-19. We set out to understand how the COVID-19 pandemic has impacted the lives of these patients in the US.
Methods: Participants in a US-wide longitudinal observational registry responded to a supplemental COVID-19 questionnaire by email on March 25, 2020 about their symptoms, COVID-19 testing, healthcare changes, and related experiences during the prior two weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free-text comment fields.

 

COVID-19 and the Clinical Hematology Laboratory
John L. Frater et al.
PMID: 32311826, 20 April 2020, in International Journal of Laboratory Hematology
The purpose of this review is to 1) provide background context about the origins and course of the pandemic 2) discuss the laboratory's role in the diagnosis of COVID-19 infection 3) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory 4) comment on the impact of COVID-19 on hematology laboratory safety, and 5) describe the impact the pandemic has had on organized national and international educational activities worldwide.

 

Comparing Rapid Scoring Systems in Mortality Prediction of Critical Ill Patients With Novel Coronavirus Disease
Hai Hu et al.
PMID: 32311790, 20 April 2020, in Academic Emergency Medicine
Objectives: Rapid and early severity-of-illness assessment appears to be important for critical ill patients with novel coronavirus disease (COVID-19). This study aimed to evaluate the performance of the rapid scoring system on admission of these patients.
Methods: 138 medical records of critical ill patients with COVID-19 were included in the study. Demographic and clinical characteristics on admission used for calculating Modified Early Warning Score (MEWS) and Rapid Emergency Medicine Score (REMS) and outcomes (survival or death) were collected for each case and extracted for analysis. All patients were divided into two age subgroups).

 

COVID-19, Immune System Response, Hyperinflammation and Repurposing Antirheumatic Drugs
Abdurrahman Tufan et al.
PMID: 32299202, 20 April 2020, in Turkish Journal of Medical Science
The SARS-CoV-2, a family member of betacoronaviruses, possesses single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines “cytokine storm” leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe disease. In this review, to gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

 

Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light‐based photochemical treatment
Shawn D. Keil et al.
PMID: 32311760, 20 April 2020, in Vox Sanguinis
Background and objective: Severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses, however viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low-risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood-borne pathogens noninfectious, while maintaining blood product quality. Here we report on the efficacy of riboflavin and UV light against the pandemic virus SARS-CoV-2 when tested in both plasma and platelets units.
Materials and methods: Stock SARS-CoV-2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titers of SARS-CoV-2 were determined by plaque assay using Vero cells. A total of five (n=5) plasma and three (n=3) platelet products were evaluated in this study.

 

Description of COVID-19 Cases Along With the Measures Taken on Prevention and Control in Zhejiang, China
Guang Wang et al.
PMID : 32311151, 20 April 2020, in Journal of Medical Virology
Background: Under the outbreak of COVID-19, it was urgent to analyze the cases from clinical features and epidemiological factors, as well as understand the effectiveness of measures taken on disease prevent and control.
Methods: A retrospective study was applied for descriptive analysis on clinical features and epidemiological factors of confirmed cases in four cities of Zhejiang. Onset-admission interval was calculated and plotted as well. The provincial measures regarding to the response of COVID-19 were summed up and sorted out.

Positive Result of Sars-Cov-2 in Faeces and Sputum From Discharged Patient With COVID-19 in Yiwu, China
Youjiang Li et al.
PMID : 32311109, 20 April 2020, in Journal of Medical Virology
Background: With the effective prevention and control of COVID - 19 in China, the number of cured cases increased significantly. Further monitoring of the disease prognosis and effective control of the "relapse" of the epidemic become the next focus of work. To analyse the clinical prognosis of discharged COVID-19 patients by monitoring their SAR-CoV-2 nucleic acid status, which may provide evidence to establish discharge standards and follow-up management for COVID-19 patients.
Methods: We included 13 discharged COVID-19 patients who were quarantined for 4-week at home. The patient's daily clinical signs were recorded and sputum and faecal specimens were regularly sent for the detection of SARS-CoV-2 nucleic acid.

Down-regulated gene expression spectrum and immune responses changed during the disease progression in COVID-19 patients
Yabo Ouyang et al.
PMID: 32307550, 20 April 2020, in Clincal Infectious Diseases
Background: WHO characterizes novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic. Here, we investigated the clinical, cytokine levels, T cell proportion and related gene expression occurring in COVID-19 patients on admission and after initial treatment. Methods: 11 patients diagnosed as COVID-19 with similar initial treatment regimen were enrolled in the hospital. Plasma cytokines, CyTOF and microfluidic qPCR for gene expression were conducted.

 

Different Longitudinal Patterns of Nucleic Acid and Serology Testing Results Based on Disease Severity of COVID-19 Patients
Zhang Yongchen et al.
PMID : 32306864, 20 April 2020, in Emerging Microbes & Infections
Effective strategy to mitigate the ongoing pandemic of 2019 novel coronavirus (COVID-19) require a comprehensive understanding of humoral responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the emerging virus causing COVID-19. The dynamic profile of viral replication and shedding along with viral antigen specific antibody responses among COVID-19 patients started to be reported but there is no consensus on their patterns. Here, we conducted a serial investigation on 21 individuals infected with SARS-CoV-2 in two medical centers from Jiangsu Province, including 11 non-severe COVID-19 patients, and 5 severe COVID-19 patients and 5 asymptomatic carriers based on nucleic acid test and clinical symptoms. The longitudinal swab samples and sera were collected from these people for viral RNA testing and antibody responses, respectively. Our data revealed different pattern of seroconversion among these groups.

Peptide-like and small-molecule inhibitors against Covid-19
Suyash Pant et al.
PMID: 32306822, 20 April 2020, in Journal of Biomolecular Structure and Dynamics
Coronavirus disease strain (SARS-CoV-2) was discovered in 2019, and it is spreading very fast around the world causing the disease Covid-19. Currently, more than 1.6 million individuals are infected, and several thousand are dead across the globe because of Covid-19. Here, we utilized the in-silico approaches to identify possible protease inhibitors against SARS-CoV-2. Potential compounds were screened from the CHEMBL database, ZINC database, FDA approved drugs and molecules under clinical trials. Our study is based on 6Y2F and 6W63 co-crystallized structures available in the protein data bank (PDB). Seven hundred compounds from ZINC/CHEMBL databases and fourteen hundred compounds from drug-bank were selected based on positive interactions with the reported binding site. All the selected compounds were subjected to standard-precision (SP) and extra-precision (XP) mode of docking. Generated docked poses were carefully visualized for known interactions within the binding site. Molecular mechanics-generalized born surface area (MM-GBSA) calculations were performed to screen the best compounds based on docking scores and binding energy values. Molecular dynamics (MD) simulations were carried out on four selected compounds from the CHEMBL database to validate the stability and interactions. MD simulations were also performed on the PDB structure 6YF2F to understand the Accepted Manuscript differences between screened molecules and co-crystallized ligand. We screened 300 potential compounds from various databases, and 66 potential compounds from FDA approved drugs. Cobicistat, ritonavir, lopinavir, and darunavir are in the top screened molecules from FDA approved drugs. The screened drugs and molecules may be helpful in fighting with SARS-CoV-2 after further studies.

 

Endothelial cell infection and endotheliitis in COVID-19
Zsuzsanna Varga et al.
20 April 2020, in The Lancet
Cardiovascular complications are rapidly emerging as a key threat in coronavirus disease 2019 (COVID-19) in addition to respiratory disease. The mechanisms underlying the disproportionate effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with cardiovascular comorbidities, however, remain incompletely understood.

Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial
Pedro M. Folegatti et al.
20 April 2020, in The Lancet – Infectious Diseases
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans.

Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial
Till Koch et al.
20 April 2020, in The Lancet – Infectious Diseases
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a respiratory disease with a case fatality rate of up to 35%. Given its potential to cause a public health emergency and the absence of efficacious drugs or vaccines, MERS is one of the WHO priority diseases warranting urgent research and development of countermeasures. We aimed to assess safety and tolerability of an anti-MERS-CoV modified vaccinia virus Ankara (MVA)-based vaccine candidate that expresses the MERS-CoV spike glycoprotein, MVA-MERS-S, in healthy adults.

 

20 April, 2020, 14.30 CET

Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study
Benjamin J. Cowling et al.
17 April 2020, in The Lancet – Public Health
Background : A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19.
Methods : We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt ) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020.

 

Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotens in converting enzyme 2 receptor
Xiangyu Chen et al.
20 April 2020, in Nature – Cellular & Molecular Immunology
Currently, there are no approved prophylactic vaccines or therapeutic drugs that are specific to COVID-19. Blocking monoclonal antibodies (mAbs), due to their extraordinary antigen specificity, are one of the best candidates for neutralizing virus infection.10,11 Therefore, identifying and cloning blocking mAbs that can specifically target surface viral proteins to block the viral entry to host cells is a very attractive approach for preventing and treating COVID-19, in particular when effective vaccines and therapeutics are unavailable in the outbreak of the COVID-19 pandemic. We then sought to identify and clone blocking mAbs from the memory B cell repertoire of recently recovered COVID-19 patients to prevent the entry of COVID-19 virus to the host cells.

 

Symptom Screening at Illness Onset of Health Care Personnel With SARS-CoV-2 Infection in King County, Washington
Eric J. Chow et al.
17 April 2020, in JAMA
Current COVID-19 HCP screening guidance includes assessing fever and respiratory symptoms (cough, shortness of breath, or sore throat) with clinical discretion for evaluation for other symptoms (eg, myalgias). We assessed the spectrum of symptoms at onset of COVID-19 among HCP and evaluated current screening criteria for identifying COVID-19 cases early in illness course.
Methods : All laboratory-confirmed SARS-CoV-2 infections in HCP residing in King County, Washington, beginning February 28, 2020, the date the first confirmed case was recognized in a King County long-term care facility,
3 through March 13, 2020, were included. HCP were tested after meeting their facilities’ signs and symptoms criteria for testing, which varied. We conducted telephone interviews soliciting the following: demographics, chronic medical conditions (eg, obesity, hypertension, diabetes, and hepatic, cardiac, and pulmonary disease), nature of patient care, occupation and work location, symptom history, days worked while symptomatic, and clinical outcome. Symptoms at illness onset included all those reported for the calendar day during which the HCP first felt unwell. Data collection was conducted as part of a public health response and was deemed by the Centers for Disease Control and Prevention to be exempt from review by an institutional review board.

 

Cardiac Involvement in COVID-19 Patients: Risk Factors, Predictors, and Complications: A Review
Ghazal Aghagoli et al.
PMID: 32306491, 19 April 2020, in Journal of Cardiac Surgery
Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19.The English literature was reviewed for papers dealing with the cardiac effects of COVID-19.

 

New-onset Acute Symptomatic Seizure and Risk Factors in Corona Virus Disease 2019: A Retrospective Multicenter Study
Lu Lu et al.
PMID: 32304092, 18 April 2020, in Epilepsia
Our aim was to clarify the incidence and risk of acute symptomatic seizures in people with coronavirus disease 2019 (COVID-19). This multicenter retrospective study enrolled people with COVID-19 from 18 January to 18 February 2020 at 42 government-designated hospitals in Hubei province, the epicenter of the epidemic in China; Sichuan province; and Chongqing municipality. Data were collected from medical records by 11 neurologists using a standard case report form. A total of 304 people were enrolled, of whom 108 had a severe condition. None in this cohort had a known history of epilepsy.

 

Broad and differential animal ACE2 receptor usage by SARS-CoV-2
Xuesen Zhao et al.
19 April 2020, in bioRxiv
The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.

 

Patient-derived mutations impact pathogenicity of SARS-CoV-2
Hangping Yao et al.
19 April 2020, in MedRxiv
The sudden outbreak of the severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. Here we report functional characterizations of 11 patient-derived viral isolates, all of which have at least one mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. We observed intrapersonal variation and 6 different mutations in the spike glycoprotein (S protein), including 2 different SNVs that led to the same missense mutation. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.

 

Antibody Detection and Dynamic Characteristics in Patients with COVID-19
Fei Xiang et al.
19 April 2020, in Clinical Infectious Diseases
Background: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed.
Methods: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate.

 

Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
Barry Rockx et al.
17 April 2020, in Science
The current pandemic coronavirus, SARS-CoV-2, was recently identified in patients with an acute respiratory syndrome, COVID-19. To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in the absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19-like disease in macaques, and provides a new model to test preventive and therapeutic strategies.

 

Cytokine release syndrome in severe COVID-19
John B. Moore and Carl H. June
17 April 2020, in Science
In December 2019, a new strain of coronavirus, severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), was recognized to have emerged in Wuhan, China. Along with SARS-CoV and Middle East respiratory syndrome– coronavirus (MERS-CoV), SARS-CoV-2 is the third coronavirus to cause severe respiratory illness in humans, called coronavirus disease 2019 (COVID-19). This was recognized as a pandemic by the World Health Organization (WHO) in March 2020 and has had considerable global economic and health impacts. Although the situation is rapidly evolving, severe disease manifested by fever and pneumonia, leading to acute respiratory distress syndrome (ARDS), has been described in up to 20% of COVID-19 cases. This is reminiscent of cytokine release syndrome (CRS)–induced ARDS and secondary hemophagocytic lymphohistiocytosis (sHLH) observed in patients with SARS-CoV and MERS-CoV as well as in leukemia patients receiving engineered T cell therapy. Given this experience, urgently needed therapeutics based on suppressing CRS, such as tocilizumab, have entered clinical trials to treat COVID-19.

 

Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2
Youngchang Kim et al.
PMID: 32304108, 17 April 2020, in Protein Science

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐ and MERS‐CoVs, the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high‐throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS‐CoV‐2 proteins and structures. Here we report two high‐resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.

 

Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus
Jaffar A. Al-Tawfiq et Ziad A. Memish
PMID: 32305045, 18 April 2020, in Seminars in Respiratory and Critical Care Medicine
Emerging infectious diseases continue to be of a significant importance worldwide with the potential to cause major outbreaks and global pandemics. In 2002, the world had witnessed the appearance of the severe acute respiratory syndrome coronavirus in China which disappeared abruptly within 6 months. About a decade later, a new and emerging novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) was described in a patient from Saudi Arabia. These two coronaviruses shared multiple similarities in the epidemiology, clinical presentations, and posed challenges in its prevention and management. Seven years since its discovery, MERS-CoV continues to be a lethal zoonotic pathogen capable of causing severe pneumonia with high case fatality rates and the ability to cause large health care-associated outbreaks.

 

17 April, 2020, 16.30 CET

Estimates of the Potential Impact of the COVID-19 Pandemic on Sexual and Reproductive Health in Low- and Middle-Income Countries
Taylor Riley et al.
16 April 2020, in Guttmacher Institute – Journal
The novel coronavirus (SARS-CoV-2) that causes COVID-19 has spread rapidly since emerging in late 2019, leading the World Health Organization (WHO) to declare the disease a global pandemic on March 11, 2020. Governments around the world have had to quickly adapt and respond to curb transmission of the virus and to provide care for the many who have been infected. The strain that the outbreak imposes on health systems will undoubtedly impact the sexual and reproductive health of individuals living in low- and middle-income countries (LMICs); however, sexual and reproductive health will also be affected by societal responses to the pandemic, such as local or national lockdowns that force health services to shut down if they are not deemed essential, as well as the consequences of physical distancing, travel restrictions and economic slowdowns.

High IL‐6/IFN‐γ ratio could be associated with severe disease in COVID‐19 patients
Francisco A. Lagunas-Rangel and Venice Chávez-Valencia
PMID: 32297995, 16 April 2020, in Journal of Medical Virology
Cytokines are important mediators of the inflammatory response, and during infection with SARS‐CoV‐2 it has been suggested that there is a cytokine storm syndrome. In this study, a meta‐analysis was performed to investigate whether the IL‐6/IFN‐γ ratio can help predict clinical severity in patients with COVID‐19.

Virological and Clinical Cure in Covid-19 Patients Treated With Hydroxychloroquine: A Systematic Review and Meta-Analysis
Phulen Sarma et al.
PMID: 32297988, 16 April 2020, in Journal of Medical Virology
Background: Following the demonstration of efficacy of hydroxychloroquine against SARS-CoV-2 in-vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis has addressed the issue of safety and efficacy of hydroxychloroquine (HCQ) in COVID-19.
Methods: We conducted a systematic review and metaanalysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure", "virological cure", "death or clinical worsening of disease", "radiological progression" and safety. RevMan was used for meta-analysis.

Sequential analysis of viral load in a neonate and her mother infected with SARS-CoV-2
Mi Seon Han et al.
PMID: 32297925, 16 April 2020, in Clinical Infectious Diseases
We report changes in viral load over time in a 27-day old neonate with COVID-19 who presented with fever, cough, and vomiting. SARS-CoV-2 RNA was detected in the nasopharynx, oropharynx, stool, saliva, plasma, and urine. The highest viral RNA copies in nasopharynx decreased over time while viral load in stool remained high.

Hospitalization Rates and Characteristics of Patients Hospitalized With Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020
Shikha Garg et al.
PMID: 32298251, 17 April 2020, in CDC - Morbidity and Mortality Weekly Report
Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. Surveillance.

Geographic Differences in COVID-19 Cases, Deaths, and Incidence - United States, February 12-April 7, 2020
CDC COVID-19 Team
PMID: 32298250, 17 April 2020, in CDC - Morbidity and Mortality Weekly Report
Community transmission of coronavirus disease 2019 (COVID-19) was first detected in the United States in February 2020. By mid-March, all 50 states, the District of Columbia (DC), New York City (NYC), and four U.S. territories had reported cases of COVID-19. This report describes the geographic distribution of laboratory-confirmed COVID-19 cases and related deaths reported by each U.S. state, each territory and freely associated state,* DC, and NYC during February 12-April 7, 2020, and estimates cumulative incidence for each jurisdiction. In addition, it projects the jurisdiction-level trajectory of this pandemic by estimating case doubling times on April 7 and changes in cumulative incidence during the most recent 7-day period (March 31-April 7). As of April 7, 2020, a total of 395,926 cases of COVID-19, including 12,757 related deaths, were reported in the United States.

Transmission of COVID-19 to Health Care Personnel During Exposures to a Hospitalized Patient - Solano County, California, February 2020
Amy Heinzerling et al.
PMID: 32298249, 17 April 2020, in CDC - Morbidity and Mortality Weekly Report
Little is known about specific risk factors for SARS-CoV-2 transmission in health care settings. To better characterize and compare exposures among HCP who did and did not develop COVID-19, standardized interviews were conducted with 37 hospital A HCP who were tested for SARS-CoV-2, including the three who had positive test results. Performing physical examinations and exposure to the patient during nebulizer treatments were more common among HCP with laboratory-confirmed COVID-19 than among those without COVID-19; HCP with COVID-19 also had exposures of longer duration to the patient.

Community Transmission of SARS-CoV-2 at Two Family Gatherings —Chicago, Illinois, February–March 2020
Isaac Ghinai et al.
PMID: 32298246, 17 April 2020, in CDC - Morbidity and Mortality Weekly Report
Most early reports of person-to-person SARS-CoV-2 transmission have been among household contacts, where the secondary attack rate has been estimated to exceed 10% (1), in health care facilities (2), and in congregate settings (3). However, widespread community transmission, as is currently being observed in the United States, requires more expansive transmission events between nonhousehold contacts. In February and March 2020, the Chicago Department of Public Health (CDPH) investigated a large, multifamily cluster of COVID-19. Patients with confirmed COVID-19 and their close contacts were interviewed to better understand nonhousehold, community transmission of SARS-CoV-2. This report describes the cluster of 16 cases of confirmed or probable COVID-19, including three deaths, likely resulting from transmission of SARS-CoV-2 at two family gatherings (a funeral and a birthday party). These data support current CDC social distancing recommendations intended to reduce SARS-CoV-2 transmission.

Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility - Four U.S. Metropolitan Areas, February 26-April 1, 2020
Arielle Lasry et al.
PMID: 32298245, 17 April 2020, in CDC - Morbidity and Mortality Weekly Report
This report presents initial data from the metropolitan areas of San Francisco, California; Seattle, Washington; New Orleans, Louisiana; and New York City, New York* to describe the relationship between timing of public policy measures, community mobility (a proxy measure for social distancing), and temporal trends in reported coronavirus disease 2019 (COVID-19) cases. Community mobility in all four locations declined from February 26, 2020 to April 1, 2020, decreasing with each policy issued and as case counts increased. This report suggests that public policy measures are an important tool to support social distancing and provides some very early indications that these measures might help slow the spread of COVID-19.

ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19
Rhian M. Touyz et al.
PMID: 32255491, 17 April 2020, in Clinical Science
Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study
Mengmeng Li et al.
PMID: 32298273, 16 April 2020, in PLOS ONE
The capacity of vertical transmission in SARS-CoV-2 remains controversial recently. Angiotensin-converting enzyme 2 (ACE2) is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. In present study, we collected the online available single-cell RNA sequencing (scRNA-seq) data to evaluate the cell specific expression of ACE2 in maternal-fetal interface as well as in multiple fetal organs. Our results revealed that ACE2 was highly expressed in maternal-fetal interface cells including stromal cells and perivascular cells of decidua, and cytotrophoblast and syncytiotrophoblast in placenta

Chest CT and Coronavirus Disease (COVID-19): A Critical Review of the Literature to Date
Constantine A. Raptis et al.
PMID: 32298149, 16 April 2020, in American Jounral of Roentgenology
Objective : Coronavirus disease (COVID-19) is a global pandemic. Studies in the radiology literature have suggested that CT might be sufficiently sensitive and specific in diagnosing COVID-19 when used in lieu of a reverse transcription–polymerase chain reaction test; however, this suggestion runs counter to current society guidelines. The purpose of this article is to critically review some of the most frequently cited studies on the use of CT for detecting COVID-19.

Geospatial Hotspots Need Point-of-Care Strategies to Stop Highly Infectious Outbreaks: Ebola and Coronavirus
Gerald J. Kost
PMID : 32298139, 16 April 2020, in
Context :Point-of-care testing (POCT), diagnostic testing at or near the site of patient care, is , that is, performed at points of need, and also , because it produces fast actionable results. Outbreaks generate geospatial "hotspots." POC strategies help control hotspots, detect spread, and speed treatment of highly infectious diseases.
Objectives. :To stop outbreaks, accelerate detection, facilitate emergency response for epidemics, mobilize public health practitioners, enhance community resilience, and improve crisis standards of care.
Data Sources :PubMed, WWW, newsprint, others were searched until COVID-19 was declared a pandemic, the US, a national emergency, and Europe, the epicenter. Coverage comprised interviews in Asia, email to/from Wuhan, papers, articles, chapters, documents, maps, flowcharts, schematics, and geospatial-associated concepts. EndNote X9.1 (Clarivate Analytics) consolidated literature as abstracts, ULRs, and PDFs, recovering 136 hotspot articles. More than 500 geospatial science articles were assessed for relevance to point-of-care testing.

Relationships among Lymphocyte Subsets, Cytokines, and the Pulmonary Inflammation Index in Coronavirus (COVID‐19) Infected Patients
Suxin Wan et al.
PMID: 32297671, 16 April 2020, in British Journal of Haematology
We explored the relationships between lymphocyte subsets, cytokines, pulmonary inflammation index (PPI), and disease evolution in patients with COVID‐19. A total of 123 patients with COVID‐19 were divided into mild and severe groups. Lymphocyte subsets and cytokines were detected on the first day of hospital admission and lung CT results were quantified by PII. Difference analysis and correlation analysis were performed on the two groups. A total of 102 mild and 21 severe patients were included in the analysis.

Saliva: potential diagnostic value and transmission of 2019-nCoV
Ruoshi Xu et al.
17 April 2020, in International Journal of Oral Science
2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.

COVID-19 tsunami: the first case of a spinal cord injury patient in Italy
Gabriele Righi et Giulio Del Popolo
17 April 2020, in Nature – Spinal Cord Series and Cases

Introduction : We present the report of the first, to our best knowledge, case of COVID-19 in a tetraplegic person.
Case presentation : A 56-year-old male with AIS A C4 tetraplegia developed fever during the night, without any prodrome. His general practitioner suspected a urinary tract infection and prescribed him antibiotic therapy. After 2 days of antibiotic therapy the fever still persisted, so the individual was admitted to the local hospital and treated with broad-spectrum antibiotics. After 2 days he was transferred to our spinal unit. Considering the worsening of the chest X-ray and fever despite 48 h of broad-spectrum antibiotic therapy, we strongly suspected viral pneumonia. SARS-CoV-2 was detected and antiviral therapy with Lopinavir/Ritonavir, associated with hydroxychloroquine, was promptly started. Fever ceased after 2 days of therapy.

Association between platelet parameters and mortality in coronavirus disease 2019:Retrospective cohort study
Yanli Liu et al.
PMID: 32297540, 16 April 2020, in Platelets
Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear.
Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models.

COVID-19, Immune System Response, Hyperinflammation and Repurposing Anti-Rheumatic Drugs
Abdurrahman Tufan et al.
PMID: 32299202, 17 April 2020, in Turkish Journal of Medical Sciences
The SARS-CoV-2, a family member of betacoronaviruses, possesses single single-stranded positive-sense RNA with typical structural proteins, involving the envelope, membrane, nucleocapsid and spike proteins that are responsible for the viral infectivity, and nonstructural proteins. The effectual host immune response including innate and adaptive immunity against SARS-Cov-2 seems crucial to control and resolve the viral infection. However, the severity and outcome of the COVID-19 might be associated with the excessive production of proinflammatory cytokines ?cytokine storm? leading to an acute respiratory distress syndrome. Regretfully, the exact pathophysiology and treatment, especially for the severe disease of COVID-19, is still uncertain. The results of preliminary studies have shown that immune-modulatory or immune-suppressive treatments such as hydroxychloroquine, interleukin (IL)-6 and IL-1 antagonists, commonly used in rheumatology, might be considered as treatment choices for COVID-19, particularly in severe lung disease. In this review, to better gain information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, we have focused the attention on the structural features of SARS-CoV-2, the host immune response against SARS-CoV-2 and its association with the cytokine storm.

Estimating the Maximum Capacity of COVID-19 Cases Manageable per Day Given a Health Care System's Constrained Resources
Vasily Giannakeas et al.
PMID: 32298412, 16 April 2020, in Annals of Internal Medicine
Objective: To develop an online tool to estimate the maximum number of COVID-19 cases that could be managed per day within the catchment area served by a health care system, given acute and critical care resource availability.
Methods: We modeled steady-state patient-flow dynamics constrained by the number of acute care beds, critical care beds, and mechanical ventilators available for COVID-19–infected patients seeking health care during the pandemic. Parameters for patient-flow dynamics were extracted from evolving data on COVID-19 and assumptions based on expert guidance. We used the package shiny within R, version 3.5.3 (R Foundation for Statistical Computing), to create the interactive tool.

Panton-Valentine Leukocidin–Secreting Staphylococcus aureus Pneumonia Complicating COVID-19
Claire Duployez et al.
PMID 32298228, 16 April 2020, in CDC – Emerging Infectious Diseases
Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.


 

16 April, 2020, 16.45 CET

CRISPR–Cas12-based detection of SARS-CoV-2
James P. Broughton et al.
16 April 2020, in Nature Biotechnology
An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (

Prognostic value of NT-proBNP in patients with severe COVID-19
Lei Gao et al.
PMID: 32293449, 15 April 2020, in Respiratory Research
Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown.
Methods: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records.

 

Evolution of CT findings in patients with mild COVID-19 pneumonia
Ting Liang et al.
PMID: 32291502, 15 April 2020, in European Radiology
Objectives : To delineate the evolution of CT findings in patients with mild COVID-19 pneumonia.
Methods : CT images and medical records of 88 patients with confirmed mild COVID-19 pneumonia, a baseline CT, and at least one follow-up CT were retrospectively reviewed. CT features including lobar distribution and presence of ground glass opacities (GGO), consolidation, and linear opacities were analyzed on per-patient basis during each of five time intervals spanning the 3 weeks after disease onset. Total severity scores were calculated.

 

Neurologic Features in Severe SARS-CoV-2 Infection
Julie Helms et al.
PMID: 32294339, 15 April 2020, in The New England Journal of Medicine
We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020.

A Clinical Study of Noninvasive Assessment of Lung Lesions in Patients With Coronavirus Disease-19 (COVID-19) by Bedside Ultrasound
Wuzhu Lu et al.
PMID: 32294796, 15 April 2020, in Ultrashall in der Medizin
Purpose This study was conducted to explore the clinical value of noninvasive assessment of bedside ultrasound in the diagnosis of lung lesions of Coronavirus Disease-19.
Methods In this retrospective study, 30 patients with Coronavirus Disease-19 admitted to our hospital from January 18 to February 5, 2020, were selected as the research subjects. All cases were examined by lung ultrasound and CT. Lung lesions were reviewed by blinded observers, with imaging scores being used to analyze the ultrasound findings of lung lesions in patients with Coronavirus Disease-19 and with chest CT being used as the reference standard. The clinical value of ultrasound in the noninvasive assessment of lung lesions was evaluated.

Temporal dynamics in viral shedding and transmissibility of COVID-19
Xi He et al.
15 April 2020, in Nature Medicine
We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector–infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.

Coronavirus Infections and Type 2 Diabetes-Shared Pathways With Therapeutic Implications
Daniel J. Drucker
PMID: 32294179, 15 April 2020, in Endocrine Reviews
Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic and viral infections. The severe acute respiratory syndrome (SARS)-CoV2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with Type 2 diabetes (T2D). Two coronavirus receptor proteins, Angiotensin Converting Enzyme 2 (ACE2) and Dipeptidyl Peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.

 

Comparison of the Indicators of Psychological Stress in the Population of Hubei Province and Non-Endemic Provinces in China During Two Weeks During the Coronavirus Disease 2019 (COVID-19) Outbreak in February 2020
Shuai Yuan et al.
PMID: 32294078, 15 April 2020, in Medical Science Monitor
BACKGROUND: During February 2020, the coronavirus disease 2019 (COVID-19) epidemic in Hubei Province, China, was at its height, requiring isolation of the population. This study aimed to compare the emotional state, somatic responses, sleep quality, and behavior of people in Hubei Province with non-endemic provinces in China during two weeks in February 2020. 
MATERIAL AND METHODS: Questionnaires were completed by 939 individuals (357 men; 582 women), including 33 from Hubei and 906 from non-endemic provinces. The Stress Response Questionnaire (SRQ) determined the emotional state, somatic responses, and behavior. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the duration of sleep and sleep quality.

SARS-CoV-2 Viral Load in Clinical Samples of Critically Ill Patients
Yongbo Huang et al.
PMID: 32293905, 15 April 2020, in American Journal of Respiratory and Critical Care Medicine
An outbreak caused by a newly identified coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China in December 2019(1), and has since spread across mainland China and to other countries. The clinical spectrum of the coronavirus disease 2019 (COVID-19) ranges from asymptomatic to severe condition with 5.0% of patients admitted to the Intensive Care Unit (ICU) (2, 3). Reverse-transcriptase–polymerase-chain-reaction (real-time RT-PCR) assays are recommended for the diagnosis of SARS-CoV-2 infection (4). A previous study reported the SARS-CoV-2 viral load in upper respiratory specimens of COVID-19 patients (5). Here, we investigate the viral load in specimens from multiple sites and the duration of viral shedding in respiratory tract samples from laboratoryconfirmed critically ill patients with COVID-19 requiring ICU admission.

 

The Impact of COPD and Smoking History on the Severity of Covid-19: A Systemic Review and Meta-Analysis
Qianwen Zhao et al.
PMID: 32293753, 15 April 2020, in Journal of Medical Virology
Aims: Comorbidities are associated with the severity of Coronavirus Disease 2019 (Covid-19). This meta-analysis aimed to explore the risk of severe Covid-19 in patients with pre-existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history.
Methods: A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22nd March 2020 from 5 Database. The language of literature included English and Chinese. The point prevalence of severe Covid-19 in patients with pre-existing COPD and those with ongoing smoking was evaluated with this meta-analysis.

 

Analysis of 92 Deceased Patients With COVID-19
Fan Yang et al.
PMID: 32293741, 15 April 2020, in Journal of Medical Virology
Objective: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19).
Method: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications.

 

Clinical Characteristics of 3,062 COVID-19 Patients: A Meta-Analysis
Jieyun Zhu et al.
PMID: 32293716, 15 April 2020, in Journal of Medical Virology
Objective: We aim to systematically review the clinical characteristics of Coronavirus disease 2019 (COVID-19).
Methods: Seven datebases were searched to collect studies about the clinical characteristics of COVID-19 from 1 January 2020 to 28 February 2020. Then, meta-analysis was performed by using Stata12.0 software.

 

Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering
Anfinrud et al.
15 April 2020, in The New England Journal of Medicine
Aerosols and droplets generated during speech have been implicated in the person-to-person transmission of viruses,
1,2 and there is current interest in understanding the mechanisms responsible for the spread of Covid-19 by these means. The act of speaking generates oral fluid droplets that vary widely in size,1 and these droplets can harbor infectious virus particles. Whereas large droplets fall quickly to the ground, small droplets can dehydrate and linger as “droplet nuclei” in the air, where they behave like an aerosol and thereby expand the spatial extent of emitted infectious particles.2 We report the results of a laser light-scattering experiment in which speech-generated droplets and their trajectories were visualized.

Presumed Asymptomatic Carrier Transmission of COVID-19
Yan Bai et al.
14 April 2020, in JAMA Network
In January 2020, we enrolled a familial cluster of 5 patients with fever and respiratory symptoms who were admitted to the Fifth People’s Hospital of Anyang, Anyang, China, and 1 asymptomatic family member. This study was approved by the local institutional review board, and written informed consent was obtained from all patients. A detailed analysis of patient records was performed.All patients underwent chest CT imaging. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid were performed using nasopharyngeal swabs (Novel Coronavirus PCR Fluorescence Diagnostic Kit, BioGerm Medical Biotechnology).

 

COVID-19 in patients with HIV: clinical case series
Jose L. Blanco et al.
15 April 2020, in The Lancet HIV
Coronavirus disease 2019 (COVID-19) has been described in only one patient with HIV in Wuhan, China,2 but case series in patients with HIV are lacking despite 37·9 million people having HIV globally.3 Here we describe, to our knowledge, the first single-centre experience of COVID-19 in patients infected with HIV-1, including clinical characteristics, antiviral and antiretroviral treatment, and outcomes.

 

COVID-19 and spinal cord injury and disease: results of an international survey
Michael D. Stillman et al.
15 April 2020, in Nature – Spinal Cord Series and Cases
Study design: An online survey. Objectives To query the international spinal cord medicine community’s engagement with and response to the novel coronavirus (COVID-19) pandemic and to assess pandemic-specific information needs and patient concerns. Setting: An international collaboration of authors and participants. Methods: Two near-identical surveys (one English and one Spanish language) were distributed via the internet. Responses from those questions shared between the surveys were pooled then analyzed; four questions’ responses (those not shared) were analyzed separately.

 

Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies
Stufang Tian et al.
14 April 2020, in Nature – Modern Pathology
Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed postmortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including three males and one female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days.

 

15 April, 2020, 16.45 CET

Experience Summary of a COVID-19 Designated Community Hospital and Its Operation Model
Qifeng Zhang et al.
PMID: 32290643, 14 April 2020, in Panminerva Medica
Object: To summarize the administration model of a COVID-19 designated hospital transformed from a community hospital to improve the emergency capacity of community hospitals and the efficiency of diagnosis and treatment of medical staff in the COVID-19 pandemic.
Methods: Analyze the surrounding environment, ward layout, area management, treatment process, medical staff and patient management of the designated community hospital.

 

The Relationship between the Migrant Population’s Migration Network and the Risk of COVID-19 Transmission in China—Empirical Analysis andPrediction in Prefecture-Level Cities
Chenjing Fan et al.
PMID : 32290445, 11 April 2020, in International Journal of Environmental Research and Public Health
The outbreak of COVID-19 in China has attracted wide attention from all over the world. The impact of COVID-19 has been significant, raising concerns regarding public health risks in China and worldwide. Migration may be the primary reason for the long-distance transmission of the disease. In this study, the following analyses were performed. (1) Using the data from the China migrant population survey in 2017 (Sample size = 432,907), a matrix of the residence–birthplace (R-B matrix) of migrant populations is constructed. The matrix was used to analyze the confirmed cases of COVID-19 at Prefecture-level Cities from February 1–15, 2020 after the outbreak in Wuhan, by calculating the probability of influx or outflow migration. We obtain a satisfactory regression analysis result (R 2 = 0.826–0.887, N = 330). (2) We use this R-B matrix to simulate an outbreak scenario in 22 immigrant cities in China, and propose risk prevention measures after the outbreak.

 

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study
PMID: 32287140, 14 April 2020, in American Journal of Gastroenterology
Objective: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms.
Methods: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020.

 

Spread of SARS-CoV-2 in the Icelandic Population
Daniel F. Gudbjartsson et al.
PMID: 32289214, 14 April 2020, in The New England Journal of Medicine
Background: During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population.
Methods: We targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons.
We sequenced SARS-CoV-2 from 643 samples.

 

Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2
Yanxiao Han et Petr Král
PMID: 32286790, 14 April 2020, in American Chemical Society
Peptide inhibitors against the SARS-CoV-2 coronavirus, currently causing a worldwide pandemic, are designed and simulated. The inhibitors are mostly formed by two sequential self-supporting α-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which bind to the SARS-CoV-2 receptor binding domains. Molecular dynamics simulations revealed that the α-helical peptides maintain their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. To provide a multivalent binding to the SARS-CoV-2 receptors, many such peptides could be attached to the surfaces of nanoparticle carriers. The proposed peptide inhibitors could provide simple and efficient therapeutics against the COVID-19 disease.

 

SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells
Soeren Lukassen et al.
PMID: 32285974, 14 April 2020, in The Embo Journal
The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.

 

Epidemiological and Clinical Features of 125 Hospitalized Patients With COVID-19 in Fuyang, Anhui, China
Ruirui Wang et al.
PMID: 32289565, 11 April 2020, in International Journal of Infectious Diseases
Objective: To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China.
Method: In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People's Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020.

 

Significance of Serology Testing to Assist Timely Diagnosis of SARS-CoV-2 Infections: Implication From a Family Cluster
Yan Xu et al.
PMID: 32286155, 14 April 2020, in Emerging Microbes and Infections
Confirmative diagnosis of SARS-CoV-2 infections has been challenged due to unsatisfactory positive rate of molecular assays. Here we identified a family cluster of SARS-CoV-2 infections, with five of six family members were SARS-CoV-2-specific immunoglobin serology testing positive, while molecular assays only detected two of this five patients even repeated twice. We comprehensively analyzed this familial cluster of cases based on the clinical characteristics, chest CT images, SARS-CoV-2 molecular detection results, and serology testing results. At last, two patients were diagnosed with COVID-19, two were suspected of COVID-19, and two were considered close contacts. Our results emphasized the significance of serology testing to assist timely diagnosis of SARS-CoV-2 infections, especially for COVID-19 close contacts screening.

 

Molecular Mechanism of Evolution and Human Infection With SARS-CoV-2
Jiahua He et al.
PMID : 32290077, 10 April 2020, in Viruses
The outbreak of a novel coronavirus, which was later formally named the severe acute respiratory coronavirus 2 (SARS-CoV-2), has caused a worldwide public health crisis. Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. Here, we have systematically studied the molecular mechanisms of human infection with SARS-CoV-2 and SARS-CoV by protein-protein docking and MD simulations. It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. In addition, the spike protein of SARS-CoV-2 has a significantly lower free energy than that of SARS-CoV, suggesting that SARS-CoV-2 is more stable and may survive a higher temperature than SARS-CoV. This provides insights into the evolution of SARS-CoV-2 because SARS-like coronaviruses have originated in bats. Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV. Thus, it is expected that SARS-CoV-2 would decrease its infection ability much faster than SARS-CoV when the temperature rises. These findings would be beneficial for the disease prevention and drug/vaccine development of SARS-CoV-2
.

 

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
Philippe Gautret et al.
PMID: 32289548, 10 April 2020, in Travel Medicine and Infectious Disease
Background: We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration.
Methods: We conducted an uncontrolled non-comparative observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU).

 

Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period
Stephen M. Kissler et al.
14 April 2020, in Science
It is urgent to understand the future of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for betacoronaviruses OC43 and HKU1 from time series data from the USA to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained since a resurgence in contagion could be possible as late as 2024.

 

 14 April, 2020, 14.30 CET

Compassionate Use of Remdesivir for Patients with Severe Covid-19
Jonathan Grein et al.
10 April 2020, in The New England Journal of Medicine
Background : Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.
Methods: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.

 

Structure of Mpro from COVID-19 virus and discovery of its inhibitors
Zhenming Jin et al.
9 April 2020, in Nature
A new coronavirus (CoV) identifed as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1–4 . Currently there are no targeted therapeutics and efective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6 . Here, we identifed a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these compounds inhibited Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efcacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specifc drugs or vaccines are available.

 

Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Yan Gao et al.
10 April 2020, in Science
A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus fulllength nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified βhairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.

 

C‐reactive protein correlates with CT findings and predicts severe COVID‐19 early
Chaochao Tan et al.
PMID : 32281668, 13 April 2020, in Journal of Medical Virology
BackgroundCOVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction.
MethodsIn total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress.

 

Neutrophil-to-lymphocyte Ratio as an Independent Risk Factor for Mortality in Hospitalized Patients With COVID-19

Yuwei Liu et al.
PMID: 32283162, 10 April 2020, in Journal of Infection
Background: Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated.
MethodsA cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well.

Clinical and Laboratory-Derived Parameters of 119 Hospitalized Patients With Coronavirus Disease 2019 in Xiangyang, Hubei Province, China
Liang Shen et al.
PMID: 32283164, 10 April 2020, in Journal of Infection
The newly emergent Coronavirus disease 2019 (COVID-19) causes severe viral pneumonia in humans and poses a serious threat to public health worldwide, with cases reported from all 6 permanently inhabited continents. Effective clinical management, based on comprehensive laboratory findings, is critical for improving the survival rates of COVID-19 patients. By now, clinical and epidemiological characteristics of COVID-19 in cities outside of Wuhan, such as Beijing1 and Wenzhou2 were described. However, it is currently unknown whether there are any markers that can be informative of mild vs. severe disease. The objective of this study is to describe the comprehensive clinical characteristics of confirmed patients with COVID-19 and explore the potential markers correlating with prognosis.

 

Lymphocyte Subset (CD4+, CD8+) Counts Reflect the Severity of Infection and Predict the Clinical Outcomes in Patients With COVID-19
Zeming Liu et al.
PMID: 32283159, 10 April 2020, in Journal of Infection.
Among the clinical and laboratory features of COVID-19, a number of abnormalities have been observed and described, the most prominent of which is total lymphopenia. Through routine blood analysis, a significant reduction in lymphocytes is frequently observed; however, there still lacks thoroughly research about the lymphocyte subset counts. Here, we aimed to investigate the changes of lymphocyte subset counts in COVID-19 patients and determine if these changes are associated with disease severity and prognosis.

 

Arterial Hypertension and Risk of Death in Patients With COVID-19 Infection: Systematic Review and Meta-Analysis
Marco Zuin et al.
PMID: 32283158, 10 April 2020, in Journal of Infection
No previous meta-analyses have globally estimated the risk of death in hypertensive patients with COVID-19 infection. We therefore perform a systematic review and meta-analysis to evaluate the risk of death in COVID-19 infection patients with and without HT.

 

Rapid Asymptomatic Transmission of COVID-19 During the Incubation Period Demonstrating Strong Infectivity in a Cluster of Youngsters Aged 16-23 Years Outside Wuhan and Characteristics of Young Patients With COVID-19: A Prospective Contact-Tracing Study
Lei Huang et al.
PMID: 32283156, 10 April 2020, in Journal of Infection
Background: The outbreak of coronavirus-disease-2019 (COVID-19) has rapidly spread to many places outside Wuhan. Previous studies on COVID-19 mostly included older hospitalized-adults. Little information on infectivity among and characteristics of youngsters with COVID-19 is available.
Methods: A cluster of 22 close-contacts of a 22-year-old male (Patient-Index) including youngsters with laboratory-confirmed COVID-19 and hospitalized close-contacts testing negative for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) in Anhui Province, China was prospectively-traced.

 

Effect of Regular Intravenous Immunoglobulin Therapy on Prognosis of Severe Pneumonia in Patients With COVID-19
Yun Xie et al.
PMID: 32283154, 10 April 2020, in Journal of Infection
At present, there is no vaccine or specific drugs for the human coronavirus . The most effective measures to 2019-nCoV are still early detection and quarantine of new sources of infection, and early diagnosis and supportive treatments for comfirmed patients. As of March 18, 2020, China had a total of 81,151 confirmed cases of COVID-19, including those in health care workers. Italy, Japan, South Korea, the United States and other countries also reported new coronavirus cases, and the total global case load outside of China was 115,682 confirmed cases.
The mortality rate of patients critically ill with the COVID-19 pneumonia is as high as 61.5% [2]. Intravenous immunoglobulin(IVIG) has been clinically used as an adjunctive drug in the treatment of severe pneumonia caused by influenza [3], but there is controversy about its therapeutic effect on COVID-19 pneumonia, despite inclusion in the seventh edition of the guidelines stating that it can be considered for use in severe and critically ill patients. For this reason, this study retrospectively observed the relationship between the prognosis of patients with severe and critical COVID-19 pneumonia and the adjuvant therapy of IVIG and explored whether IVIG could improve the clinical symptoms, laboratory examination and prognosis of these patients.

 

The effect of corticosteroid treatment onpatients with coronavirus infection: asystematic review and meta-analysis
Zhenwei Yang et al.
10 April 2020, in Journal of Infection
Objubei province - the epicentre of the outbreak - had been reported. Since late January, massive public health interventions have been implemented nationwide to contain the outbreak. We provide an impact assessment of the transmissibility and severity of COVID-19 during the first wave in mainland Chinese locations outside Hubei. 

Methods : We estimated the instantaneous reproduction number (Rt ) of COVID-19 in Beijing, Shanghai, Shenzhen, Wenzhou, and the ten Chinese provinces that had the highest number of confirmed COVID-19 cases; and the confirmed case-fatality risk (cCFR) in Beijing, Shanghai, Shenzhen, and Wenzhou, and all 31 Chinese provinces. We used a susceptible–infectious–recovered model to show the potential effects of relaxing containment measures after the first wave of infection, in anticipation of a possible second wave.

 

Prediction models for diagnosis and prognosis of covid-19infection: systematic review and critical appraisal
Laure Wynants et al.
7 April 2020, in the BMJ
Objective : To review and critically appraise published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at risk of being admitted to hospital for covid-19 pneumonia. Design Rapid systematic review and critical appraisal.
Data sources : PubMed and Embase through Ovid, Arxiv, medRxiv, and bioRxiv up to 24 March 2020.
Study selection : Studies that developed or validated a multivariable covid-19 related prediction model.
Data extraction : At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).

 

Effective containment explains subexponential growth in recent confirmed COVID-19 cases in China
Benjamin F. Maier et Dirk Brockmann
8 April 2020, in Science
The recent outbreak of COVID-19 in Mainland China was characterized by a distinctive subexponential increase of confirmed cases during the early phase of the epidemic, contrasting an initial exponential growth expected for an unconstrained outbreak. We show that this effect can be explained as a direct consequence of containment policies that effectively deplete the susceptible population. To this end, we introduce a parsimonious model that captures both, quarantine of symptomatic infected individuals as well as population-wide isolation practices in response to containment policies or behavioral changes and show that the model captures the observed growth behavior accurately. The insights provided here may aid the careful implementation of containment strategies for ongoing secondary outbreaks of COVID-19 or similar future outbreaks of other emergent infectious diseases.

Susceptibility of ferrets, cats, dogs, and other domesticatedanimals to SARS–coronavirus 2
Jianzhong Shi et al.
8 April 2020, in Science
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19, which was first reported in Wuhan, China in December, 2019. Despite the tremendous efforts to control the disease, COVID-19 has now spread to over 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are completely unknown. Here, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. We found experimentally that cats are susceptible to airborne infection. Our study provides important insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.

 


 

08 April, 2020, 12.45 CET

COVID-19 and cancer: what we know so far
Peter Sidaway
7 April 2020, in Nature reviews Clinical Oncology
Infection with SARS-CoV-2, resulting in coronavirus disease (COVID-19), can lead to acute respiratory distress syndrome (ARDS) requiring admission to an intensive care unit (ICU), and sometimes death, in a subset of patients. So far, we know that individuals ≥60 years of age and/or those with a supressed immune system are particularly vulnerable to COVID-19, although how these risks apply to patients with cancer remains unclear. Several reports are beginning to emerge.

SARS-CoV-2 detection in patients with influenza-like illness
Wen-Hua Kong et al.
7 April 2020, in Nature Microbiology
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.

Rapid detection of African swine fever virus using Cas12a-based portable paper diagnostics
Shuhan Lu et al.
7 April 2020, in Cell Discovery
African swine fever virus (ASFV) is a dsDNA virus responsible for a severe, highly contagious, and lethal disease affecting both domestic and wild pigs. ASFV has brought enormous economic loss to a number of countries, and effective vaccine and therapy are still lacking. Therefore, a rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we developed a Cas12a-mediated portable paper assay to rapidly and precisely detect ASFV.We identified a robust set of crRNAs that recognized the highly conserved region of essential ASFV genes. The Cas12a-mediated detection assay showed low tolerance for mismatch mutations, and no cross-reactivity against other common swine pathogens. We further developed a paper-based assay to allow instrument-free detection of ASFV. Specifically, we applied gold nanoparticle–antibody conjugate to engineer homemade strips and combined it with Cas12a-mediated ASFV detection.

The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis
Kunihiro Matsushita et al.
7 April 2020, in medRxiv
Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses.

Analysis and Applications of Non-Adaptive and Adaptive Group Testing Methods for COVID-19
Cassidy Mentus et al.
7 April 2020, in medRxiv
Testing strategies for Covid-19 to maximize number of people tested is urgently needed. Recently, it has been demonstrated that RT-PCR has the sensitivity to detect one positive case in a mixed sample 32 cases [9]. In this paper we propose non-adaptive and adaptive group testing strategies based on generalized binary splitting (GBS) [2] where we restrict the group test to the largest group that can be used. The method starts by choosing a group from the population to be tested, performing a test on the combined sample from the entire group and progressively splitting the group further into subgroups. Compared to individual testing at 4% prevalence we save 74% at 1% we save 91% and at 1% we save 97% of tests. We analyze the number of times each sample is used and show the method is still efficient if we resort to testing a case individually if the sample is running low.

Study of Epidemiological Characteristics and In-silico Analysis of the Effect of Interventions in the SARS-CoV-2 Epidemic in India
Archisman Mazumder et al.
7 April 2020, in medRxiv
After SARS-CoV-2 set foot in India, the Indian Government took a number of steps to limit the spread of the disease in the country. This study involves assessing how the disease affected the population in the initial days of the epidemic. Data was collected from government controlled and crowdsourced websites and then put through analysis and calculations. With a study on age and sex parameters of 413 patients, the median age of the affected individuals was found out to be 36 years (IQR 25-54 years) with 20-39 years males being the most affected group. The number of affected males (66.34%) was more than that of the females(33.66%).Using SIR model, the range of contact rate(β) of India was calculated and the role of public health interventions was assessed which proved that the interventions were effective for a little while but the effect reduced due to violations.

COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics
Shovolnal Roy
7 April 2020, in medRxiv
COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution.

A Bayesian Logistic Growth Model for the Spread of COVID-19 in New York
Svetoslav Bliznashki
7 April 2020, in medRxiv
We use Bayesian Estimation for the logistic growth model in order to estimate the spread of the coronavirus epidemic in the state of New York. Models weighting all data points equally as well as models with normal error structure prove inadequate to model the process accurately. On the other hand, a model with larger weights for more recent data points and with t-distributed errors seems reasonably capable of making at least short term predictions.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy
Giacomo Grasselli et al.
6 April 2020, in Jama Network
Objective :To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy.
Design, Setting, and Participants : Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020.
Exposures : SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs.
Main Outcomes and Measures : Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network.

Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Young-Il Kim et al.
PMID: 32259477, 5 April 2020, in ScienceDirect
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication.

Novel Coronavirus Infection in Children Outside of Wuhan, China
Qinxue Shen et al.
PMID: 32259403, 5 April 2020, in Pediatric Pulmonology
Background: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited.
Methods: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020.

Maternal and Perinatal Outcomes with COVID‐19: a systematic review of 108 pregnancies
Mehreen Zaigham et Ola Andersson
PMID: 32259279, 7 April 2020, in Acta Obstetricia et Gynecologica Scandinavica

Introduction: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy.
Material and methods: We searched databases for all case reports and series from February 12 to April 4, 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed.

 


 

07 April, 2020, 1.45 CET

School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review
Russel M. Viner et al.
6 April 2020, in The Lancet Child and Adolescent Health
In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.

Structural Variations in Human ACE2 may Influence its Binding with SARS‐CoV‐2 Spike Protein
Mushtaq Hussain et al.
PMID: 32249956, 6 April 2020, in Journal of Medical Virology
The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared to the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein in turn lead to the cross species transmission of the virus, genetic variations in the host receptor ACE2, may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modelling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein respectively.

An Analysis of Spatiotemporal Pattern for COIVD-19 in China Based on Space-Time Cube
Chunbao Mo et al.
PMID: 3224995, 6 April 2020, in Journal of Medical Virology
This study seeks to examine and analyze the spatial and temporal patterns of COVID-19 outbreaks and identify the spatiotemporal distribution characteristics and changing trends of cases. Hence, local outlier analysis and emerging spatiotemporal hot spot analysis were performed to analyze the spatiotemporal clustering pattern and cold\hot spot trends of COVID-19 cases based on space-time cube during the period from January 23, 2020 to February 24, 2020.

A Comparative-Descriptive Analysis of Clinical Characteristics in 2019-Coronavirus-infected Children and Adults
Ya-Nah Han et al.
PMID: 32249943, 6 April 2020, in Journal of Medical Virology
Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan.

COVID‐19 and Urology: A Comprehensive Review of the Literature
Stefano Puliatti et al.
PMID: 32249538, 6 April 2020, in BJUI International
Covid‐19 pandemic is the newest and biggest global health threat worldwide. Medical and surgical priorities were changed dramatically at the time of this pandemic. Postponement for all outpatient and elective activities to save facilities and resources for urgent cases and Covid‐19 patients was adopted by most of hospitals in the affected countries. Over the coming weeks healthcare workers including urologists will be facing increasingly difficult challenges and consequently they should adopt sufficient protection strategies to guard against infection when dealing with COVID‐19 patients. In this review we discussed the impact of Covid‐19 on global health, urinary tract and uro‐oncologic surgeries . Additionally, we reviewed some of the available recommendations reported on oncological surgeries practice during this pandemic.

 

Computational Studies of Drug Repurposing and Synergism of Lopinavir, Oseltamivir and Ritonavir Binding With SARS-CoV-2 Protease Against COVID-19
Nisha Muralidharan et al.
PMID: 32248766, 6 April 2020, in Journal of Biomolecular Structure and Dynamics
A novel coronavirus (SARS-CoV-2) has caused a major outbreak in humans all over the world, and it is the latest pandemic in the series of other infectious diseases. The concept of drug repurposing has been used successfully for many years for known diseases. Considering the emergency and urgency, drug repurposing concept is being explored for coronavirus disease (COVID-19) as well. Recently, the combination of three known drugs, lopinavir, oseltamivir and ritonavir has been proposed to control the virulence to a great extent in COVID-19 affected patients within 48 hours. Hence, we tried to understand the effect of synergism of these drugs against the SARS-CoV-2 protease using sequential docking studies. As a result, combination of three drugs showed a better binding energy than that of individual drugs. Further, the complex was subjected to molecular dynamics simulations to get insights into the stability of the complex, considering the simultaneous interactions between three drugs and the protein. The protein complexed with three drugs remained stable during the simulations. Hence, these drugs can be explored further for drug repurposing against the successful inhibition of COVID-19.

Maternal and Neonatal Outcomes of Pregnant Women With COVID-19 Pneumonia: A Case-Control Study
Na Li et al.
PMID: 32249918, 30 March 2020, in Clinical Infectious Diseases
Background: The ongoing epidemics of coronavirus disease 2019 (COVID-19) have caused serious concerns about its potential adverse effects on pregnancy. There are limited data on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia.
Methods: We conducted a case-control study to compare clinical characteristics, maternal and neonatal outcomes of pregnant women with and without COVID-19 pneumonia.


 

06 April, 2020, 1.30 CET

Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-C-reactive Protein Ratio in Patients With Severe Coronavirus Disease 2019 (COVID-19): A Meta-Analysis
Francisco Alejandro Lagunas-Rangel
PMID: 32242950, 3 April 2020, in Journal of Medical Virology
Since March 11, 2020, the World Health Organization (WHO) defined Coronavirus disease 2019 (COVID-19) as a pandemic, with a series of confirmed cases that currently exceeded 300,000 people worldwide and with approximately 14,500 deaths. Accumulated evidence suggests that a subgroup of patients with severe COVID-19 could have a dysregulation of the immune response that allows the development of viral hyperinflammation. Thus, all patients with severe COVID-19 should be screened for hyperinflammation using laboratory parameters in order to improve mortality. Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-C-reactive protein ratio (LCR) are established inflammation markers that reflect systemic inflammatory response, and both are available in almost all laboratories. In this study, a meta-analysis was performed to investigate whether NLR and LCR values can help predict clinical severity in patients with COVID-19.

 

Imaging and Clinical Features of Patients With 2019 Novel Coronavirus SARS-CoV-2: A Systematic Review and Meta-Analysis
Yinghao Cao et al.
PMID : 32242947, 3 April 2020, in Journal of Medical Virology
Background: Currently, the epidemic of Coronavirus Disease 2019 (COVID-19) has begun to spread worldwide. We aim to explore reliable evidences for the diagnosis and treatment of the COVID-19 by analyzing all the published studies by Chinese scholars on the clinical and imaging features in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2.
Methods: We searched five medical databases including two Chinese and three English databases for all published articles on COVID-19 since the outbreak. A random-effects model was designed, and the imaging and clinical data from all studies were collected for meta-analysis.

 

Clinical Features of 85 Fatal Cases of COVID-19 From Wuhan: A Retrospective Observational Study
Yingzhen Du et al.
PMID: 32242738, 3 April 2020, in American Journal of Respiratory and Critical Care Medicine
Background: The global death toll from COVID-19 virus exceeds 21000. The risk factors for death were attributed to advanced age and co-morbidities, but haven't been accurately defined.
Objectives: To report the clinical features of 85 fatal cases with COVID-19 in two hospitals in Wuhan.
Method: Medical records of 85 fatal cases of COVID-19 between January 9 and February 15, 2020 were collected. Information recorded included medical history, exposure history, comorbidities, symptoms, laboratory findings, CT scans and clinical management.

 

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19
Eu Suk Kim et al.
PMID: 32242348, 6 April 2020, in Journal of Korean Medical Science
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness.

 

Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection
Lu Lin et al.
PMID: 32241899, 2 April 2020, in Gut
Objective: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.
Design: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues.

 

Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immunecross-reactivity with SARS-CoV
Xiuyuan Ou et al.
27 March 2020, in Nature
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

 

Evolving epidemiology and transmission dynamics ofcoronavirus disease 2019 outside Hubei province, China: a descriptive and modelling study
Juanjuan Zhang et al.
2 April 2020, in The Lancet Infectious Diseases
Background The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began in Wuhan city, Hubei province, in December, 2019, and has spread throughout China. Understanding the evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information from official public sources on laboratory-confirmed cases reported outside Hubei in mainland China for the period of Jan 19 to Feb 17, 2020. We used the date of the fourth revision of the case definition (Jan 27) to divide the epidemic into two time periods (Dec 24 to Jan 27, and Jan 28 to Feb 17) as the date of symptom onset. We estimated trends in the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt ) at the provincial level.

 


 

3 April, 2020, 1.30pm CET

Liver Impairment in COVID-19 Patients: A Retrospective Analysis of 115 Cases from a Single Center in Wuhan City, China
Yafei Zhang et al.
PMID: 32239796, 3 April 2020, in Liver International
Background: The SARS-CoV-2 pandemic is an ongoing global health emergency. The aim of our study was to investigate the changes of liver function and its clinical significance in COVID-19 patients.
Method: This retrospective, single-center study was conducted on 115 confirmed cases of COVID-19 in Zhongnan hospital of Wuhan University from Jan 18 to Feb 22, 2020. Liver function and related indexes were analyzed to evaluate its relationship with disease progression in COVID-19 patients.

 

Identification of Chymotrypsin-like Protease Inhibitors of SARS-CoV-2 Via Integrated Computational Approach
Salman Ali Khan et al.
PMID: 32238094, 2 April 2020, in Journal of Biomolecular Structure and Dynamics
Recently, the world has witnessed outbreak of a novel Coronavirus (SARS-CoV-2), the virus which initially emerged in Wuhan, China has now made its way to a large part of the world, resulting in a public emergency of international concern. The functional importance of Chymotrypsin-like protease (3CLpro) in viral replication and maturation turns it into an attractive target for the development of effective antiviral drugs against SARS and other coronaviruses. At present, there is no standard drug regime nor any vaccine available against the infection. The rapid development and identification of efficient interventions against SARS-CoV-2 remains a major challenge. Based on the available knowledge of closely related coronavirus and their safety profiles, repurposing of existing antiviral drugs and screening of available databases is considered a near term strategic and economic way to contain the SARS-CoV-2 pandemic. Herein, we applied computational drug design methods to identify Chymotrypsin-like protease inhibitors from FDA approved antiviral drugs and our in-house database of natural and drug-like compounds of synthetic origin. As a result three FDA approved drugs ( Remdesivir, Saquinavir and Darunavir) and two natural compounds (. flavone and coumarine derivatives) were identified as promising hits. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior, stability of protein-ligand contact, and binding affinity of the hit compounds.

 

Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020
Anne Kimball et al.
PMID: 32240128, 3 April 2020, in Morbidity and Mortality Weekly Report (CDC)
What is already known about this topic?
Once SARS-CoV-2 is introduced in a long-term care skilled nursing facility (SNF), rapid transmission can occur.
What is added by this report?
Following identification of a case of coronavirus disease 2019 (COVID-19) in a health care worker, 76 of 82 residents of an SNF were tested for SARS-CoV-2; 23 (30.3%) had positive test results, approximately half of whom were asymptomatic or presymptomatic on the day of testing.

 

SARS-CoV-2 Is Not Detectable in the Vaginal Fluid of Women With Severe COVID-19 Infection
Lin Qiu et al.
PMID: 32241022, 2 April 2020, in Clinical Infectious Diseases
Background : Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is mainly spread through respiratory droplets or direct contact. But the infection condition of genital system is still unknown. This study aimed to evaluate whether or not SARS-CoV-2 is found in the vaginal fluid of women with COVID-19 illness.
Methods : 10 women with confirmed severe COVID-19 pneumonia admitted to in Tongji Zhongfa Hospital Intensive care union(ICU) ward from Feb 4, 2020 to Feb 24, 2020 were included. Clinical records, laboratory results, and computer tomography(CT)-scan examination were retrospectively reviewed. The evidence of genital infection potential was accessed by testing for the presence of SARS-CoV-2 in vaginal fluids obtained from vaginal swab samples. Reverse transcriptase polymerase chain reaction(RT-PCR) was used to confirm the SARS-CoV-2 infection in vaginal fluids.

 

Computational inference of selection underlying the evolution of the novel coronavirus, SARS-CoV-2
Rachele Cagliani et al.
PMID: 32238584, 1 April 2020, in Journal of Virology
The novel coronavirus (SARS-CoV-2) recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this aim, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral ORFs evolved under strong to moderate purifying selection.

 

Clinical Findings in a Patient With Hemophilia A Affected by COVID-19
Dongyan Cui et al.
PMID : 32239590, 1 April 2020, in Haemophilia
Minimal information is available regarding COVID-19 patients with hemophilia A. Herein, we retrospectively analyzed the epidemiological, clinical, laboratory and radiological characteristics, treatment and clinical outcomes of an infected patient with hemophilia A in Wuhan. This case report may be a good example in the management of mild COVID-19 cases with hemophilia A.

 

SARS-CoV-2 Spike Protein Favors ACE2 From Bovidae and Cricetidae
Junwen Luan et al.
PMID: 32239522, 1 April 2020, in The Journal of Medical Virology
SARS-CoV-2 causes the recent COVID-19 public health crisis. Bat is the widely believed original host of SARS-CoV-2. However, its intermediate host before transmitting to human is not clear. Some studies proposed pangolin, snake or turtle as the intermediate hosts. ACE2 is the receptor for SARS-CoV-2, which determines the potential host range for SARS-CoV-2. Based on the structural information of the complex of human ACE2 and SARS-CoV-2 RBD, we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae and Cetacea maintained the majority of key residues in ACE2 for associating with SARS-CoV-2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS-CoV-2 RBD. We found that nearly half of the key residues in turtle, snake and bird are changed. The simulated structures showed several key contacts with SARS-CoV-2 RBD in turtle and snake ACE2 were abolished. Our study demonstrated that neither snake nor turtle was the intermediate hosts for SARS-CoV-2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. Our study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS-CoV-2.

 

Isolation and Full-Length Genome Characterization of SARS-CoV-2 From COVID-19 Cases in Northern Italy
Danilo Licastro et al.
PMID: 32238585, 1 April 2020, in Journal of Virology
In December 2019, the novel coronavirus Severe Acquired Respiratory Syndrome SARS-CoV-2 emerged in the city of Wuhan in the Hubei province, People's Republic of China, as the etiologic agent of coronavirus disease 2019 (COVID-19), which has hence spread worldwide causing a global pandemic. Cell culture supernatant from passage 1 (P1) of four isolates were collcted, and RNA was extracted with QiAmp Viral RNA mini kit (Qiagen ) and quantified with an in vitro transcribed RNA standard.

COVID-19 in Hemodialysis Patients: A Report of 5 Cases
Rui Wang et al.
PMID: 32240718, 31 March 2020, in American Journal of Kidney Diseases
In December 2019, an outbreak of coronavirus disease (COVID-19) due to the novel SARS-CoV-2 virus began in China and spread rapidly worldwide. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this Case Report, we describe the clinical and epidemiological features of COVID-19 in 201 maintenance hemodialysis patients in Zhongnan Hospital of Wuhan university, including 5 maintenance hemodialysis patients who contracted COVID-19 disease.

 


 

2 April, 2020, 3pm, CET

COVID-19 pandemic in west Africa
Melissa Martinez-Alvarez et al.
1 April 2020, in The Lancet Global Health
The coronavirus disease 2019 (COVID-19) outbreak, which started in the Hubei province of China in 2019, has now spread to all continents, affecting 177 countries by March 27, 2020. Successful efforts in containing the COVID-19 virus in Asia resulted in WHO declaring Europe as the epicentre of the disease on March 13. Whether warmer temperatures will slow the spread of the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a point of much speculation. This hypothesis has led some European countries to produce initial policies relying on decreased transmission rates during the summer months, and the belief that African countries will face smaller epidemics than their European counterparts. However, no strong evidence base exists for such claims; SARS-CoV-2 might have simply arrived later to warmer countries.

Epidemiological analysis of COVID-19 and practical experience from China
Qing Ye et al.
PMID: 32237160, 1 April 2020, in Journal of Medical Virology
The rapid spread of the epidemic has aroused widespread concern in the international community. SARS-COV-2 originated from Wuhan's Huanan wholesale seafood market, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS-COV-2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large-scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and MERS, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.

Differences Between COVID-19 and Suspected Then Confirmed SARS-CoV-2-negative Pneumonia: A Retrospective Study From a Single Center
Xinyi Chen et al.
PMID: 32237148, 1 April 2020, in Journal of Medical Virology
Coronavirus disease 2019 (COVID-19) broke out in Wuhan, Hubei, China in December 2019. Tens thousands of people have been infected with the disease. Our aim was to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients from SARS-CoV-2-negative patients. We retrospectively compared the data of COVID-19 patients with those of suspected and confirmed SARS-CoV-2-negative patients (control patients). There were 78 COVID-19 patients and 26 control patients, whose median ages were significantly different (P=0.001). The percentage of COVID-19 patients admitting exposure to Wuhan was obviously higher than that of control patients (X2 =29.130, P<0.001). Fever and cough appeared more frequently in COVID-19 patients than in the control patients. The routine blood work-up parameters of COVID-19 patients did not change much and their mean counts were in normal range. There were 38.5% of control patients had higher procalcitonin (PCT) levels than 0.5ng/ml, which was significantly higher than that percentage of COVID-19 patients (X2 =22.636, P <0.05), and COVID-19 patients were also more likely to have decreased or normal urea and creatinine levels than control patients (X2 =24.930, 8.480, P <0.05).Younger age, exposure to Wuhan, fever, cough, and slight changes in routine blood work-up parameters, urea and creatinine were important features discriminating COVID-19 from control patients. Slightly increased, but far less than 0.5ng/ml, PCT levels also differentiated COVID-19 patients from control patients.

 

Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis
Xiu-Wu Pan et al.
PMID: 32236644, 31 March 2020, in Intensive Care Medicine
Tens of thousands of humans were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a short period of time, and the infection spread quickly across China and throughout the world. Acute kidney injury (AKI) is one of the important complications of the 2019 novel coronavirus disease (COVID19), occurring in 0.5–7% of cases and in 2.9–23% of ICU patients. However, whether the AKI of COVID-19 is caused by a coronavirus-induced cytopathic efect or cytokine storm-induced systemic infammatory response remains unclear.

A Comparative Study of Chest Computed Tomography Features in Young and Older Adults With Corona Virus Disease (COVID-19)
Tingting Zhu et al.
PMID: 32235187, 31 March 2020, in Jounal of Thoracic Imaging
The objective here is to analyze the most common computed tomography (CT) findings of pneumonia caused by new coronavirus in younger patients (60 and younger) and older adults (older than 60). The chest CT images of 72 symptomatic patients with corona virus disease (COVID-19) were analyzed retrospectively, including 44 younger patients (47.5±8.7 y old) and 28 older patients (68.4±6.0 y old). CT findings including density (pure ground-glass opacities, ground-glass opacities with consolidation, consolidation), the number of lobes involved, lesion distribution, and the main accompanying signs were analyzed and compared.

Spatial-temporal Distribution of COVID-19 in China and Its Prediction: A Data-Driven Modeling Analysis
Rui Hang et al.
PMID: 32235084, 31 March 2020, in The Jounral of Infection in Developing Countries
Currently, the outbreak of COVID-19 is rapidly spreading especially in Wuhan city, and threatens 14 million people in central China. In the present study we applied the Moran index, a strong statistical tool, to the spatial panel to show that COVID-19 infection is spatially dependent and mainly spread from Hubei Province in Central China to neighbouring areas. Logistic model was employed according to the trend of available data, which shows the difference between Hubei Province and outside of it. We also calculated the reproduction number R0 for the range of [2.23, 2.51] via SEIR model. The measures to reduce or prevent the virus spread should be implemented, and we expect our data-driven modeling analysis providing some insights to identify and prepare for the future virus control.

Molecular Characterization of SARS-CoV-2 in the First COVID-19 Cluster in France Reveals an Amino-Acid Deletion in nsp2 (Asp268Del)
Antonin Bal et al.
PMID: 32234449, 28 March 2020, in Clinical Microbiology and Infection
In December 2019, a novel coronavirus emerged in China, causing outbreaks of unexplained pneumonia [1]. The virus was subsequently identified as a beta-coronavirus and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is responsible of the coronavirus disease 2019 (COVID-19) pandemic which includes asymptomatic, upper, and lower respiratory tract infections. Among the first European cases of COVID-19, 6 were associated with a cluster of transmission in the French Alps in late January 2020 [2]. The index case of this cluster travelled from Singapore to France and went back to the United Kingdom (UK) where he was tested positive for SARS-CoV-2 on February 6th. Here, we aimed to investigate the French cases related to this cluster using metagenomic next-generation sequencing (mNGS) analysis.

Spinal anaesthesia for patients with coronavirus disease 2019 and possible transmission rates in anaesthetists: retrospective, single-centre, observational cohort study
Qi Zhong et al.
PMID: 32234250, 28 March 2020, in British Journal of Anaesthesia
Background: The safety of performing spinal anaesthesia for both patients and anaesthetists alike in the presence of active infection with the novel coronavirus disease 2019 (COVID-19) is unclear. Here, we report the clinical characteristics and outcomes for both patients with COVID-19 and the anaesthetists who provided their spinal anaesthesia.
Methods: Forty-nine patients with radiologically confirmed COVID-19 for Caesarean section or lower-limb surgery undergoing spinal anaesthesia in Zhongnan Hospital, Wuhan, China participated in this retrospective study. Clinical characteristics and perioperative outcomes were recorded. For anaesthesiologists exposed to patients with COVID-19 by providing spinal anaesthesia, the level of personal protective equipment (PPE) used, clinical outcomes (pulmonary CT scans), and confirmed COVID-19 transmission rates (polymerase chain reaction [PCR]) were reviewed.

 

01 April, 2020, 2pm, CET

The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients
Jing Yuan et al.
PMID: 32227274, 30 March 2020, in Inflammation Research
This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People’s Hospital, enrolled from Jan 5 to Feb 13, 2020. The clinical and laboratory fndings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected.

 

SARS-CoV-2–Positive Sputum and Faeces After Conversion of Pharyngeal Samples in Patients With COVID-19
Chen Chen et al.
PMID: 32227141, 30 March 2020, in Annals of Internal Medicine
Objective: To assess the results of RT-qPCR for SARS–CoV2 RNA of sputum and fecal samples from a group of patients after conversion of their pharyngeal samples from positive to negative.

 

Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia
Fan Wang et al.
PMID: 32227123, 30 March 2020, in The Journal of Infectious Diseases
Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19.The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed.

 

The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2
Liang Chen et al.
PMID: 32227090, 30 March 2020, in Cardiovascular Research
Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients. Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.

 

Atlas of ACE2 gene expression in mammals reveals novel insights in transmisson of SARS-Cov-2
Kun Sun et al.
31 March 2020, in bioRxiv
COVID-19 has become a worldwide pandemic. It is caused by a novel coronavirus named SARS-CoV-2 with elusive origin. SARS-CoV-2 infects mammalian cells by binding to ACE2, a transmembrane protein. Therefore, the conservation of ACE2 and its expression pattern across mammalian species, which are yet to be comprehensively investigated, may provide valuable insights into tracing potential hosts of SARS-CoV-2. Methods: We analyzed gene conservation of ACE2 across mammals and collected more than 140 transcriptome datasets from human and common mammalian species, including presumed hosts of SARS-CoV-2 and other animals in close contact with humans. In order to enable comparisons across species and tissues, we used a unified pipeline to quantify and normalize ACE2 expression levels.

Sequence variation among SARS-CoV-2 isolates in Taiwan
Yu-Nong Gong et al.
31 March 2020, in bioRxiv
Taiwan experienced two waves of imported cases of coronavirus disease 2019 (COVID-19), first from China in January to late February, followed by those from other countries starting in early March. Additionally, several cases could not be traced to any imported cases and were suspected as sporadic local transmission. Twelve full viral genomes were determined in this study by Illumina sequencing either from virus isolates or directly from specimens, among which 5 originated from clustered infections. Phylogenetic tree analysis revealed that these sequences were in different clades, indicating that no major strain has been circulating in Taiwan. A deletion in open reading frame 8 was found in one isolate. Only a 4-nucleotide difference was observed among the 5 genomes from clustered infections.

 

31 March, 2020, 3pm, CET

Estimates of the severity of coronavirus disease 2019: a model-based analysis
Robert Verity et al.
30 March 2020, in The Lancet, Infectious Diseases
In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases.

We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalization.

 

Covid-19 in Critically ill Patients in the Seattle Region — Case Series
Pavan K. Bhatraju et al.
30 March 2020, in The New England Jounral of Medicine

Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up.

 

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study
Tao Chen et al.
26 March 2020, in The BMJ
Objective: To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.
Design: Retrospective case series.
Setting: Tongji Hospital in Wuhan, China.
Participants: Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.
Main outcome measures: Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.


This article has a correction, please see here


Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)
Tao Guo et al.
27 March 2020, in JAMA Cardiology

Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. The objective is to evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020.

 

Antibodies in Infants Born to Mothers With COVID-19 Pneumonia
Hui Zeng et al.
26 March 2020, in JAMA
Tests for IgG and IgM antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became available in February 2020. On March 4, 2020, the seventh edition of the New Coronavirus Pneumonia Prevention and Control Protocol for the novel coronavirus disease 2019 (COVID-19) was released by the National Health Commission of the People’s Republic of China and added serological diagnostic criteria. A previous study of 9 pregnant women and their infants found no maternal-infant transmission of SARS-CoV-2 based on reverse transcriptase–polymerase chain reaction (RT-PCR). We applied these new criteria to 6 pregnant women with confirmed COVID-19 and their infants because serologic criteria would allow more detailed investigation of infection in newborns.


Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn
Lan Dong et al.
26 March 2020, in JAMA
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly infectious, with multiple possible routes of transmission controversy exists regarding whether SARS-CoV-2 can be transmitted in utero from an infected mother to her infant before birth. A series of 9 pregnant women found no mother-child transmission. We report a newborn with elevated IgM antibodies to SARS-CoV-2 born to a mother with coronavirus disease 2019 (COVID-19).

30 March, 2020, 3.30pm, CET

Genomic Characterisation and Phylogenetic Analysis of SARS-CoV-2 in Italy
Gianguglielmo Zehender et al.
PMID: 32222993, 29 March 2020, in Journal of Medical Virology

This report describes the isolation, molecular characterisation and phylogenetic analysis of the first three complete genomes of SARS‐CoV‐2 isolated from three patients involved in the first outbreak of COVID‐19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS‐CoV‐2 was present in Italy weeks before the first reported cases of infection.

 

Detectable SARS-CoV-2 Viral RNA in Feces of Three Children During Recovery Period of COVID-19 Pneumonia
Tongqiang Zhang et al.
PMID: 32222992, 29 March 2020, in Journal of Medical Virology
Coronavirus Disease 2019 (COVID-19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After its first occurrence in Wuhan of China from December 2019, COVID-19 rapidly spread around the world. According to the World Health Organization (WHO) statement on March 13, 2020, there had been over 132,500 confirmed cases globally. Nevertheless, the case reports of children are rare, which result in the lack of evidence for preventing and controlling of children's infection. Here, we report 3 cases of SARS-CoV-2 infected children diagnosed from February 3 to February 17, 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after treatment, with the nucleic acid of throat swab turning negative within 14, 11, 7 days after diagnosis respectively. However, after been discharged, all the three cases were tested SARS-CoV-2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal-oral transmission of SARS-CoV-2 infection, especially for children cases

 

Clinical Characteristics of 54 Medical Staff With COVID-19: A Retrospective Study in a Single Center in Wuhan, China
Jiaojiao Chu et al.
PMID: 32222986, 29 March 2020, in Journal of Medical Virology
54 cases of SARS-Cov-2 infected medical staff from Tongji Hospital between January 7th to February 11th of 2020 were analyzed in this retrospective study. Clinical and epidemiological characteristics were compared between different groups by statistical method.

 

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease
Antoney J. Ferrey et al.
PMID: 32222713, 28 March 2020, in American Journal of Nephrology
Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.

 

Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients
Fengting Yu et al.
PMID: 32221523, 28 March 2020, in Clinical Infectious Disease
Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription PCR (RT-PCR) method has limitations for clinical diagnosis and treatment. Here, a total of 323 samples from 76 COVID-19 confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based two target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging.

 

Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia
Siyu Chen et al.
PMID: 32222119, 28 March 2020, in Journal of Medical Virology
In this article, we aim to evaluate the pregnant women infected with coronavirus disease 2019 (COVID-19) and provide help for clinical prevention and treatment.All 5 cases of pregnant women confirmed COVID-19 were collected among patients who admitted in Maternal and Child Hospital of Hubei Province between January 20 and February 10, 2020.

 

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019
Juanjuan Zhao et al.
PMID: 32221519, 28 March 2020, in Clinical Infectious Disease
The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. Here, a total of 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n=535) collected during the hospitalization were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2. The dynamics of antibodies with the disease progress was analyzed.

 

68 Consecutive Patients Assessed for COVID-19 Infection; Experience From a UK Regional Infectious Disease Unit
Nicholas Easom et al.
PMID: 32223012, 29 March 2020, in Influenza and other respiratory viruses
Assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for COVID-19 illness, has been a major activity of infection services since the first reports of cases in December 2019. We report a series of 68 patients assessed at a Regional Infection Unit in the UK.
Between the 29th Jan 2020 - 24th Feb 2020 demographic, clinical, epidemiological and laboratory data were collected. We compared clinical features between patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment.

 

Clinical and epidemiological features of 36 children withcoronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study
Haiyan Qiu et al.
25 March 2020, in The Lancet, Infectious Diseases
Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients’ epidemiological and clinical features.

Clinical and virological data of the first cases of COVID-19in Europe: a case series
François-Xavier Lescure et al.
27 March 2020, in The Lancet, Infectious Diseases
In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.

Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington
Temet M. McMichael et al.
27 March 2020, in The New England Journal of Medicine
Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health–Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control.

 

27 March, 2020, 2pm CET

The Effect of Human Mobility and Control Measures on the COVID-19 Epidemic in China
Moritz U. G. Kraemer et al.
PMID: 32213647, 25 March 2020, in Science
The ongoing COVID-19 outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions have been undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.

 

Structural and biochemical characterization of SADS‐CoV Papain Like protease 2
Lu Wang et al.
PMID: 32216114, 26 March 2020, in Protein Science
Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel coronavirus that is involved in severe diarrhea disease in piglets, causing considerable agricultural and economic loss in China. The emergence of this new coronavirus increases the importance of understanding SADS-CoV as well as antivirals. Coronaviral proteases, including main proteases and papain-like proteases (PLP), are attractive antiviral targets because of their essential roles in polyprotein processing and thus virus maturation. Here, we describe the biochemical and structural identification of recombinant SADS papain-like protease 2 (PLP2) domain of nsp3. The SADS-CoV PLP2 was shown to cleave nsp1 proteins and also peptides mimicking the nsp2|nsp3 cleavage site and also had deubiquitinating and deISGynating activity by in vitro assay. The crystal structure adopts an architecture resembling that of PLPs from other coronaviruses. We characterize both conserved and unique structural features likely directing the interaction of PLP2 with the substrates, also including the tentative mapping of active site and other essential residues. These results provide a foundation for understanding the molecular basis of coronaviral PLPs's catalytic mechanism and for the screening and design of therapeutics to combat infection by SADS coronavirus.

 

Covid‐19 and the Digestive System
Sunny H. Wong et al.
PMID: 32215956, 25 March 2020, Journal of Gastroenterology and Hepatology
The novel coronavirus disease (Covid‐19) is currently causing a major pandemic. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a member of the Betacoronavirus genus that also includes the SARS‐CoV and Middle East Respiratory Syndrome Coronavirus (MERS‐CoV). While patients typically present with fever and a respiratory illness, some patients also report gastrointestinal symptoms such as diarrhoea, vomiting and abdominal pain. Studies have identified the SARS‐CoV‐2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS‐CoV‐2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control. In this article, we review the important gastrointestinal aspects of the disease.

 

CT morphology of COVID-19: Case report and review of literature
Okka Wilkea Hamer et al.
PMID: 32215898, 26 March 2020, in Roefo
The number of patients with COVID-19 is rapidly increasing in Europe. The lethality of the disease appears to be higher than that of seasonal flu, for example, especially in older patients. RT-PCR is the gold standard for establishing a diagnosis. In many patients, chest CT seems to provide an image that is suggestive for diagnosis. The cardinal signs are ground glass opacities, consolidation and crazy paving, predominantly located in the periphery of the lower lobes. This CT morphology can support the diagnosis and differentiation from other viral pneumonia. This is particularly important because RT-PCR can initially provide a false negative result.



CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19)
Kunwei Li et al.
PMID: 32215691, 25 March 2020, in European Radiology
Objectives here is to explore the relationship between the imaging manifestations and clinical classification of COVID-19. We conducted a retrospective single-center study on patients with COVID-19 from Jan. 18, 2020 to Feb. 7, 2020 in Zhuhai, China. Patients were divided into 3 types based on Chinese guideline: mild (patients with minimal symptoms and negative CT findings), common, and severe-critical (patients with positive CT findings and different extent of clinical manifestations). CT visual quantitative evaluation was based on summing up the acute lung inflammatory lesions involving each lobe, which was scored as 0 (0%), 1 (1–25%), 2 (26–50%), 3 (51–75%), or 4 (76–100%), respectively. The total severity score (TSS) was reached by summing the five lobe scores. The consistency of two observers was evaluated. The TSS was compared with the clinical classification. ROC was used to test the diagnosis ability of TSS for severe-critical type.

 

Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility
Jasper Fuk-Woo Chan et al.
PMID: 32215622, 26 March 2020, in Clinical Infectious Disease
A novel, readily available, and physiological small animal model of Syrian hamster for SARSCoV-2 infection that recapitulates the clinical, virological, histopathological, and immunological characteristics of human disease was established to study the pathogenesis, transmission, and passive immunisation effect of COVID-19.

 

Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) —United States, February 12–March 16, 2020
CDC COVID Respose team
PMID: 32214079, 27 March 2020
Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries (1). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic (2). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19–associated illness and death than are younger persons (3). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years (3). In this report, COVID-19 cases in the United States that occurred during February 12–March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities.

26 March, 2020, 3pm CET

Using the spike protein feature to predict infection risk and monitor the evolutionary dynamic of coronavirus
Xiao-Li Qiang et al.
PMID: 32209118, 25 March 2020, in Infectious Diseases of Poverty
Coronavirus can cross the species barrier and infect humans with a severe respiratory syndrome. SARS-CoV-2 with potential origin of bat is still circulating in China. In this study, a prediction model is proposed to evaluate the infection risk of non-human-origin coronavirus for early warning.

 

Analysis of Epidemiological and Clinical Features in Older Patients With Corona Virus Disease 2019 (COVID-19) Out of Wuhan
Jiangshan Lian et al.
PMID: 32211844, 25 March 2020, in Clinical Infectious Diseases
The outbreak of COVID-19 has become a big threat to China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 out of Wuhan. A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from Jan 17 to Feb 12, 2020. Epidemiological, clinical and treatment data were analyzed between those older (≥60y) and younger (<60y) patients.

Evolutionary Trajectory for the Emergence of Novel Coronavirus SARS-CoV-2
Saif Ur Rehman et al.
PMID: 
32210130, 23 March 2020, in Pathogens
Over the last two decades, the world experienced three outbreaks of coronaviruses with elevated morbidity rates. Currently, the global community is facing emerging virus SARS-CoV-2 belonging to Betacoronavirus, which appears to be more transmissible but less deadly than SARS-CoV. The current study aimed to track the evolutionary ancestors and different evolutionary strategies that were genetically adapted by SARS-CoV-2. Our whole-genome analysis revealed that SARS-CoV-2 was the descendant of Bat SARS/SARS-like CoVs and bats served as a natural reservoir. SARS-CoV-2 used mutations and recombination as crucial strategies in different genomic regions including the envelop, membrane, nucleocapsid, and spike glycoproteins to become a novel infectious agent. We confirmed that mutations in different genomic regions of SARS-CoV-2 have specific influence on virus reproductive adaptability, allowing for genotype adjustment and adaptations in rapidly changing environments. Moreover, for the first time we identified nine putative recombination patterns in SARS-CoV-2, which encompass spike glycoprotein, RdRp, helicase and ORF3a. Six recombination regions were spotted in the S gene and are undoubtedly important for evolutionary survival, meanwhile this permitted the virus to modify superficial antigenicity to find a way from immune reconnaissance in animals and adapt to a human host. With these combined natural selected strategies, SARS-CoV-2 emerged as a novel virus in human society.

 

The Clinical Characteristics of Myocardial injury 1 in Severe and Very Severe Patients with 2019 Novel Coronavirus Disease
Bo Zhou et al.
PMID: 32209382, 21 March 2020, in Journal of Infection
The 2019 Novel coronavirus disease (COVID-19) has drawn global intensive attention. .Previous studies suggest that severe COVID-19 may present with acute cardiac injury. However, few have investigated the cardiac lesion markers and their correlation to disease severity. In this letter, we explored the cardiac lesion biomarkers in patients with severe and very severe COVID-19.

 

Comparisons of nucleic acid conversion time of SARS-CoV-2 of different samples in ICU and non-ICU patients
Zhixiong Fang et al.
PMID: 32209381, 21 March 2020, in Journal of Infection
Since outbreak of unexplained pneumonia cases in Wuhan, China in December, 2019, the coronavirus disease 2019 (COVID-19) has spread to more than 90 countries. By 7th March, the infection of SARS-CoV-2 has influenced 101,918 patients globally. Recommended by World Health Organization (WHO), a positive real-time reverse transcriptase polymerase chain-reaction (RT-PCR) result could confirm the diagnosis of suspected COVID-19 patients. However, there still lacks thoroughly research concerning nucleic acid conversion time among different samples in COVID-19 patients. Here we compared the nucleic acid conversion time of SARS-CoV-2 in different samples of intensive care unit (ICU) and non-ICU patients and analyzed their characteristics.

 

Clinical Characteristics of Fatal and Recovered Cases of Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Retrospective Study
Deng Yan et al.
PMID: 32209890, 20 March 2020, in Chinese Medical Journal
The 2019 novel coronavirus (2019-nCoV) has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study is performed to analyze the clinical characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher's exact tests as appropriate.

 

Role of Changes in SARS-CoV-2 Spike Protein in the Interaction with the Human ACE2 Receptor: An in silico Analysis
Joseph T. Ortega et al.
PMID: 32210742, 18 March 2020
Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.

 

Unrevealing Sequence and Structural Features of Novel Coronavirus Using in silico Approaches: The Main Protease as Molecular Target
Joseph T. Ortega et al.
PMID: 32210741, 17 March 2020
Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.

 

25 March 2020, 2.30pm CET

Identifying Locations with Possible Undetected Imported Severe Acute Respiratory Syndrome Coronavirus 2 Cases by Using Importation Predictions
Pablo Martinez De Salazar et al.
PMID: 32207679, 24 March 2020, in Emerging Infectious Diseases
Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exported from mainland China could lead to self-sustained outbreaks in other countries. By February 2020, several countries were reporting imported SARS-CoV-2 cases. To contain the virus, early detection of imported SARS-CoV-2 cases is critical. We used air travel volume estimates from Wuhan, China, to international destinations and a generalized linear regression model to identify locations that could have undetected imported cases. Our model can be adjusted to account for exportation of cases from other locations as the virus spreads and more information on importations and transmission becomes available. Early detection and appropriate control measures can reduce the risk for transmission in all locations.

 

Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)
Swatantra Kumar et al.
PMID: 32206694, March 2020, in Virus Disease
The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools.

 

Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia
Ruihong Sun
PMID: 32207255, March 2020, in Korean Journal of Radiology
The coronavirus disease 2019 (COVID-19) pneumonia is a recent outbreak in mainland China and has rapidly spread to multiple countries worldwide. Pulmonary parenchymal opacities are often observed during chest radiography. Currently, few cases have reported the complications of severe COVID-19 pneumonia. We report a case where serial follow-up chest computed tomography revealed progression of pulmonary lesions into confluent bilateral consolidation with lower lung predominance, thereby confirming COVID-19 pneumonia. Furthermore, complications such as mediastinal emphysema, giant bulla, and pneumothorax were also observed during the course of the disease.

 

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China
Fang Zheng et al.
PMID: 32207032, 24 March 2020, Current Medical Science
Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. 

 


 

24 March, 2020, 2.45pm CET

Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019
Jianbo Lai et al.
23 March 2020, in JAMA Network
What factors are associated with mental health outcomes among health care workers in China who are treating patients with coronavirus disease 2019 (COVID-19)? The aim of this paper is to assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China.

 

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine
Wanbo Tai et al.
PMID: 32203189, 19 March 2020, in Cellular & Molecular Immunology
The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.

 

Spike protein recognition of mammalian ACE2 predicts the host rangeand an optimized ACE2 for SARS-CoV-2 infection
Junwen Luan et al.
PMID: 32201080, 19 March 2020, in ScienceDirect
SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for bothSARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the keyresidues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets(dog and cat), pangolin andCircetidaemammals remained the most of key residues for association with Sprotein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinesehamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. Weidentified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in humanACE2. Ourfinding will provide important insights into the host range of SARS-CoV-2 and a new strategyto design an optimized ACE2 for SARS-CoV-2 infection.

Functional exhaustion of antiviral lymphocytes in COVID-19 patients
Meijuan Zheng et al.
PMID: 32203188, 19 March 2020, in Cellular & Molecular Immunology
Cytotoxic lymphocytes such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are necessary for the control of viral infection, and the functional exhaustion of cytotoxic lymphocytes is correlated with disease progression.2 However, whether the cytotoxic lymphocytes in patients infected with SARS-CoV-2 become functionally exhausted has not been reported.
We showed that the total number of NK and CD8+ T cells was decreased markedly in patients with SARS-CoV-2 infection. The function of NK and CD8+ T cells was exhausted with the increased expression of NKG2A in COVID-19 patients. Importantly, in patients convalescing after therapy, the number of NK and CD8+ T cells was restored with reduced expression of NKG2A. These results suggest that the functional exhaustion of cytotoxic lymphocytes is associated with SRAS-CoV-2 infection. Hence, SARS-CoV-2 infection may break down antiviral immunity at an early stage.

Elevated exhaustion levels and reduced functional diversity ofT cells in peripheral blood may predict severe progression inCOVID-19 patients
Hong-Yi Zheng et al.
PMID: 32203186, 17 March 2020, in Cellular & Molecular Immunology
Recent studies have shown that in addition to dyspnea, hypoxemia, and acute respiratory distress, lymphopenia, and cytokine release syndrome are also important clinical features in patients with severe SARS-CoV-2 infection.3 This suggests that homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. To provide direct evidence on leukocyte homeostasis, we studied the immunological characteristics of peripheral blood leukocytes from 16 patients admitted to the Yunnan Provincial Hospital of Infectious Diseases, Kunming, China.

 

23 March, 2020, 4pm CET

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
Linlin Zhang et al.
PMID: 32198291, 20 March 2020, in Science
The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, 3CLpro), due to its essential role in processing the polyproteins that are translated from the viral RNA. We report the X-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. Based on the structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 Mpro The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

 

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)
Li Guo et al.
PMID: 32198501, 21 March 2020, in Clinical Infectious Diseases
We here aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. The host humoral response against SARS-CoV-2 including IgA, IgM and IgG response were examined by using an ELISA based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but had typical manifestation). The diagnostic value of IgM was evaluated in this cohort.

 

The Clinical Characteristics of Pneumonia Patients Co-Infected With 2019 Novel Coronavirus and Influenza Virus in Wuhan, China
Qiang Ding et al.
PMID: 32196707, 20 March 2020, in Journal of Medical Virology
In this study, we describe the clinical characteristics of those patients who got infected with COVID‐19 as well as influenza virus. Common symptoms at onset of illness included fever (5 [100%] patients), Cough (5 [100%] patients), shortness of breath (5 [100%] patients), nasal tampon (3 [60%] patients), pharyngalgia (3 [60%] patients), myalgia (2 [40%] patients), fatigue (2 [40%] patients), headache (2 [40%] patients), and expectoration (2 [40%] patients). The laboratory results showed that compared to the normal values, the patients' lymphocytes were reduced (4 [80%] patients), and liver function ALT and AST (2 [40%] patients, 2 [40%] patients) and C‐reactive protein (4 [80%] patients) were increased when admitted to hospital. They stayed in hospital for 14, 30, 17, 12, and 19 days (28.4±7.02), respectively. The main complications for the patients were acute respiratory distress syndrome (ARDS) (1 [20%] patients), acute liver injury (3 [60%] patients), and diarrhea (2 [40%] patients).

Effect of Gastrointestinal Symptoms on Patients Infected With COVID-19
Zili Zhou et al.
PMID: 32199880, 18 March 2020
Fever and respiratory symptoms tend to be initial and major, whereas gastrointestinal symptoms (GI symptoms) were also observed in a significant portion of patients. RT-PCR positive findings from patients’ stool further revealed that COVID-19 may spread by fecal-oral transmission. In addition, recent studies have shown that the receptor of ACE2, which is essential for cells infected by COVID-19, is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon. These results further confirmed that the digestive system may be a potential route for COVID-19 infection. Therefore, a study exploring the correlation between GI symptoms and patients’ symptoms, diagnosis, treatment, and outcomes is of great importance to improve the diagnosis and treatment plan of novel coronavirus-infected pneumonia (NCIP).

Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2
Ye Qiu et al.
PMID: 32199943, 18 March 2020, in ScienceDirect
SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2. As a result, we predicted that SARS-CoV-2 tends to utilize ACE2s of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2.

Global epidemiology of coronavirus disease 2019: disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status
Chih-Cheng Lai et al.
PMID: 32199877, 18 March 2020, in ScienceDirect
It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan. So far, COVID-19 has affected 84,503 patients in 57 countries/territories and caused 2,924 deaths in nine countries. However, the epidemiology data differ across countries. Although China had higher morbidity and mortality than other sites, the number of new cases per day in China is lesser than that outside of China since February 26, 2020. The incidence ranged from 61.4 per 1,000,000 people in Republic of Korea to 0.0002 per 1,000,000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and February 29, 2020) was greatest in China (1,320.85 per day), followed by Republic of Korea (78.78 per day), Iran (43.11 per day), and Italy (30.62 per day). However, the DCI in other countries/territories were less than 10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and at once daily press conference by government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of February 29, 2020) with a DCI of 1 case per day in Taiwan, which was much lower than that of nearby countries, such as Republic of Korea and Japan. Additionally, the incidence and mortality were correlated with DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.

 

20 March, 2020, 5pm CET

Evaluation of the Effectiveness of Surveillance and Containment Measures for the First 100 Patients with COVID-19 in Singapore — January 2–February 29, 2020
Yixiang Ng et al.
PMID: 32191691, 20 March 2020, in Centers for Disease Control and Prevention
This report analyzes the first 100 COVID-19 patients in Singapore to determine the effectiveness of the surveillance and containment measures. Rapid identification and isolation of cases, quarantine of close contacts, and active monitoring of other contacts have been effective in suppressing expansion of the outbreak and have implications for other countries experiencing outbreaks.

 

Analysis of COVID-19 infection spread in Japan based on stochastic transition model
Kenji Karako et al.
PMID: 32188819, 19 March 2020
To assess the effectiveness of response strategies of avoiding large gatherings or crowded areas and to predict the spread of COVID-19 infections in Japan, we developed a stochastic transmission model by extending the Susceptible-Infected-Removed (SIR) epidemiological model with an additional modeling of the individual action on whether to stay away from the crowded areas.

Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages
Aaron Volk et al.
PMID: 32188729, 18 March 2020, in Journal of Virology
Coronaviruses encode multiple interferon antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists: the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type, DUBmut, and EndoUmut viruses in infected macrophages.

 

Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China
Mingli Yuan et al.
PMID: 32191764, 19 March 2020
Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47–69). 17 patients discharged in recovered condition and 10 patients died in hospital.

 

Natural Small Molecules as Inhibitors of Coronavirus Lipid-Dependent Attachment to Host Cells: A Possible Strategy for Reducing SARS-COV-2 Infectivity?
Mirko Baglivo et al.
PMID: 32191676, 19 March 2020, in Acta Biomedica
Viral infectivity depends on interactions between components of the host cell plasma membrane and the virus envelope. Here we review strategies that could help stem the advance of the SARS-COV-2 epidemic.

Artificial Intelligence Distinguishes COVID-19 From Community Acquired Pneumonia on Chest CT
Lin Li et al.
PMID: 32191588, 20 March 2020
It is desirable to develop automatic and accurate detection of COVID-19 using chest CT. Purpose To develop a fully automatic framework to detect COVID-19 using chest CT and evaluate its performances. Materials and Methods In this retrospective and multi-center study, a deep learning model, COVID-19 detection neural network (COVNet), was developed to extract visual features from volumetric chest CT exams for the detection of COVID-19. Community acquired pneumonia (CAP) and other non-pneumonia CT exams were included to test the robustness of the model. The datasets were collected from 6 hospitals between August 2016 and February 2020. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity.

 

Temporal Changes of CT Findings in 90 Patients with COVID-19 Pneumonia: A Longitudinal Study
Yuhui Wang et al.
PMID: 32191587, 19 March 2020
CT plays a central role in the diagnosis and management of COVID-19 pneumonia. Previous efforts to analyze CT manifestations have continued. Some papers demonstrated the CT findings to be diverse, with the main abnormalities including ground-glass opacity and consolidation. Pan described the evolution of CT findings in 21 mild COVID-19 pneumonia patients. A better understanding of the progression of CT findings in COVID-19 pneumonia may help facilitate accurate diagnosis and disease stage. Thus, we performed a longitudinal study to analyze the serial CT findings in patients with COVID19 pneumonia for temporal change.

 

19 March 2020, 3pm CET

Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis
Dehan Liu et al.
PMID: 32186894, 18 March 2020, in American Journal of Roentgenology
The purpose of this study was to describe the clinical manifestations and CT features of coronavirus disease (COVID-19) pneumonia in 15 pregnant women and to provide some initial evidence that can be used for guiding treatment of pregnant women with COVID-19 pneumonia.

 

Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China
Joseph T. Wu et al.
19 March 2020, in Nature Medicine
A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9–2.1%), which is substantially lower than both the corresponding crude or naïve confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator1 of deaths/deaths + recoveries (2,169/2,169 + 17,572 = 11%) as of 29 February 2020.



Coronaviruses and the cardiovascular system: acute and long-term implications  
Tian-Yuan Xiong et al.
PMID: 32186331, 18 March 2020, in European Heart Journal
Acute and chronic cardiovascular complications of pneumonia are common and result from various mechanisms, including relative ischaemia, systemic inflammation, and pathogen-mediated damage. There is, however, only limited published data concerning cardiovascular presentations in the wake of viral epidemics. The present COVID-19 outbreak emphasizes the need for greater awareness of the immediate and long-term cardiovascular implications of viral infection and the significant gaps in knowledge that future research will need to address.


Influenza-associated pneumonia as reference to assess seriousness of coronavirus disease (COVID-19).
Kristin Tolksdorf et al.
PMID: 32186278, 18 March 2020, in Europe's journal on infectious disease surveillance, epidemiology, prevention and control.
With a simple approach, we give a preliminary assessment of individual seriousness of COVID-19 using well-described case series of hospitalised COVID-19 pneumonia patients from the cities of Wuhan, Beijing, Shenzhen and the provinces of Hubei and Zhejiang [5-12]. We defined a reference group from a well-known setting: in 73 German sentinel hospitals, we extracted the data of all inpatients diagnosed with pneumonia (International Classification of Diseases, 10th revision codes J12-J18, primary diagnosis [13]) that were admitted during three consecutive weeks, after the start and before the peak of the influenza epidemic in the years 2015 to 2019. We compared severity parameters that were described for COVID-19 patients (acute respiratory distress syndrome, ventilation, intensive care, case fatality) with those from the German sentinel system.


The difference in the incubation period of 2019 novel coronavirus (SARS-CoV-2) infection between travelers to Hubei and non-travelers: The need of a longer quarantine period
Char Leung
PMID: 32183920, 18 March 2020, in Cambridge University Press
Different preventive measures have been implemented by health authorities with the 14-day quarantine being the commonly used. While previous studies have estimated the incubation period of SARS-CoV-2 to help determining the length of quarantine, it has recently been observed that some patients rather had mild symptoms such as cough and low-grade fever or even no symptoms and that the incubation period might have been 24 days , constituting greater threats to the effectiveness of entry screening. Against this background, the present work estimated the distribution of incubation periods of patients infected in and outside Hubei.


SARS-CoV-2 Infection in Children
Xiaoxia Lu et al.
PMID: 32187458, 18 March 2020, in The New England Journal of Medicine.
A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age. In order to determine the spectrum of disease in children, we evaluated children infected with SARS-CoV-2 and treated at the Wuhan Children’s Hospital, the only center assigned by the central government for treating infected children under 16 years of age in Wuhan. Both symptomatic and asymptomatic children with known contact with persons having confirmed or suspected SARS-CoV-2 infection were evaluated.

Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020  
Pete Kinross et al.
PMID: 32186277, 19 March 2020, in Europe's journal on infectious disease surveillance, epidemiology, prevention and control.
In this study, we assess the trends in the cumulative incidence of COVID-19 in each European Union/European Economic Area (EU/EEA) country and the United Kingdom (UK) and compare them to that of Hubei Province, China. We also compare the current number of COVID-19 cases in EU/EEA countries and the UK with that in Italy during 31 January–15 March 2020.

 

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19
Bin Cao et al.
PMID: 32187464, 18 March 2020, in The New England Journal of Medicine.
We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2 ) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2 ) to the fraction of inspired oxygen (Fio2 ) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020
Yuanyuan Xing
PMID: 32183934, March 2020, Europe's journal on infectious disease surveillance, epidemiology, prevention and control.
At 5 March 2020, a total of 80,409 COVID-19 cases and 3,012 deaths (3.75%) have been reported in mainland China. The 52,045 recovered cases (64.73%) were further quarantined at home for at least 2 weeks. However, potential infectivity of these recovered cases was still unclear. Thus, we implemented consecutive virus surveillance among medical staff recovered from COVID-19 at our hospital and aimed to investigate their potential infectivity after discharge.

Spatial transmission of COVID-19 via public and private transportation in China
Ruizhi Zheng et al.
PMID: 32184132, 14 March 2020, in Travel Medicine and Infectious Disease
In order to evaluate the role of public transportation in the spatial transmission of COVID-19, we searched daily flights, buses, and trains from Wuhan to these cities in January.

Comparison of clinical characteristics of coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) as experienced in Taiwan  
Yu-Jang Su & Yen-Chun Lai
PMID: 32184131, 14 March 2020, in Travel Medicine and Infectious Disease
We analysed the clinical picture of the first ten coronavirus disease (COVID-19) cases in Taiwan till 31 January 2020, and compared them to SARS in terms of epidemiology, symptoms, laboratory characteristics, and outcome.


 

 18 March 2020, 3pm CET

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA
Isaac Ghinai et al.
PMID: 32178768, 17 March 2020
This article describes the first person-to-person transmission of COVID-19 in the USA, including the clinical and laboratory features of both patients and the assessment and monitoring of several hundred individuals with potential exposure to SARS-CoV-2.

A 55-Day-Old Female Infant Infected With COVID 19: Presenting With Pneumonia, Liver Injury, and Heart Damage
Yuxia Cui et al.
PMID: 32179908, 17 March 2020, in The Journal of Infectious Diseases.
We report a 55-day-old case with COVID-19 confirmed in China and describe the identification, diagnosis, clinical course, and treatment of the patient, including the disease progression from day 7 to day 11 of illness. This case highlights that children with COVID-19 can also present with multiple organ damage and rapid disease changes.

Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China
Y
anrong Wang et al
PMID: 32179910, 17 March 2020, in The Journal of Infectious Diseases.
We study the epidemiological and clinical outcomes of 55 asymptomatic carriers who were laboratory-confirmed positive for the SARS-Coronavirus-2 by testing the nucleic acid of the pharyngeal swab samples. The evidence showed that asymptomatic carriers occurred more often in middle-aged people who had close contact with infected family members. The majority of the cases developed to be mild and ordinary COVID-19 during hospital.

Clinical features of pediatric patients with COVID‑19: a report of two family cluster cases
Li-Na Ji 1 et al.
PMID: 32180140, 16 March 2020
We retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described.

An Analysis of 38 Pregnant Women With COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes
David A Schwartz
PMID: 32180426, 17 March 2020
This communication reviews the effects of two previous coronavirus infections - severe acute respiratory syndrome (SARS) caused by SARS-CoV and the Middle East respiratory syndrome (MERS) caused by MERS-CoV - on pregnancy outcomes. In addition, it analyzes literature describing 38 pregnant women with COVID-19 and their newborns in China to assess the effects of SARS-CoV-2 on the mothers and infants including clinical, laboratory and virologic data, and the transmissibility of the virus from mother to fetus. This analysis reveals that unlike coronavirus infections of pregnant women caused by SARS and MERS, in these 38 pregnant women COVID-19 did not lead to maternal deaths. Importantly, and similar to pregnancies with SARS and MERS, there were no confirmed cases of intrauterine transmission of SARS-CoV-2 from mothers with COVID-19 to their fetuses


Correlation between travelers departing from Wuhan before the Spring Festival and subsequent spread of COVID-19 to all provinces in China

Ping Zhong et al.
PMID: 32181483, 17 March 2020, in the Journal of Travel Medicine.
The aim of this essay is to explore the correlation between travelers departing from Wuhan before the Spring Festival and the extent of amplification of the outbreak of COVID-19 in China.

The Positive Impact of Lockdown in Wuhan on Containing the COVID-19 Outbreak in China 
Hien Lau et al.
PMID: 32181488  17 March 2020, in the Journal of Travel Medicine.
We analyzed available data on the development of confirmed domestic and international COVID-19 cases before and after lockdown measures. We evaluated the correlation of domestic air traffic to the number of confirmed COVID-19 cases and determined the growth curves of COVID-19 cases within China before and after lockdown as well as after changes in COVID-19 diagnostic criteria.

Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia
Rui Han et al.
PMID: 32181672  17 March 2020, in the American Journal of Roentgenology
The purpose of this study was to investigate early clinical and CT manifestations of coronavirus disease (COVID-19) pneumonia.


Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression

Lan Zhu et al.
PMID: 32181990, 17 March 2020.
We report here the clinical features and therapeutic course of the first reported renal transplant recipient with confirmed COVID-19 pneumonia. This is a 52-year-old man who received kidney transplantation 12 years ago. His overall clinical characteristics (symptoms, laboratory examinations, and chest CT) were similar to those of non-transplanted COVID-19 patients. 

Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with Corona Virus Disease‐19
Rong Qu et al.
PMID: 32181903, 17 March 2020, in the Journal of Medical Virology
Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to-lymphocyte ratio(PLR)were a concern. We sought to describe the platelet feature of these cases.


 

17 March 2020, 3pm CET

 

Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand.

Neil M Ferguson et al.

Here we present the results of epidemiological modelling which has informed policymaking in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published microsimulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission.

 

Potential Impact of Seasonal Forcing on a SARS-CoV-2 Pandemic

Neher Richard A. et al.
16 March 2020, Swiss Med Wkly. 2020;150:w20224

Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions.

Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China
Zhongliang Wang et al.
16 March 2020
A review of 69 patients who were hospitalized in Union hospital in Wuhan between January 16 to January 29, 2020. All patients were confirmed to be infected with SARS-CoV-2 and the final date of follow-up was February 4, 2020.


Estimation of Coronavirus Disease 2019 (COVID-19) Burden and Potential for International Dissemination of Infection From Iran

Ashleigh R Tuite et al.

PMID: 31176272, 16 March 2020, in Ann Intern Med. 2020 
The objective of this article is to quantify the COVID-19 outbreak size in Iran on the basis of known exported case counts and air travel links between Iran and other countries and to anticipate where infections originating in Iran may spread next.

 

Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals

Ivan Seah et Rupesh Agrawal

PMID: 32175797, 16 March 2020

The ocular implications of human CoV infections have not been widely studied. However, CoVs have been known to cause various ocular infections in animals. Clinical entities such as conjunctivitis, anterior uveitis, retinitis, and optic neuritis have been documented in feline and murine models. In this article, the current evidence suggesting possible human CoV infection of ocular tissue is reviewed. The review article will also highlight animal CoVs and their associated ocular infections. We hope that this article will serve as a start for further research into the ocular implications of human CoV infections.


A tug-of-war between severe acute respiratory syndrome coronavirus 2 and host antiviral defence: lessons from other pathogenic viruse

Sin-Yee Fung et al.
14 March 2020 in Emerging Microbes & Infections, 9:1, 558-570.
Here, we review the discovery, zoonotic origin, animal hosts, transmissibility and pathogenicity of SARS-CoV-2 in relation to its interplay with host antiviral defence. A comparison with SARS-CoV, Middle East respiratory syndrome coronavirus, community-acquired human coronaviruses and other pathogenic viruses including human immunodeficiency viruses is made. We summarize the current understanding of the induction of a proinflammatory cytokine storm by other highly pathogenic human coronaviruses, their adaptation to humans and their usurpation of the cell death programmes.

 


 

16 March 2020, 3pm CET

COVID-19 in the Shadows of MERS-CoV in the Kingdom of Saudi Arabia.

Barry M et al.

PMID: 32175703, 10 March 2020

This challenge will now be faced by the whole global health community dealing with COVID-19 since both coronaviruses have a similar presentation. Those patients should now be tested for both MERS-CoV and SARS-CoV-2 simultaneously, and with the continuing wide international spread of SARS-CoV-2, the travel history to China in the last 14 days will be of less significance.

 

Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients.

Salehi S. et al.

PMID: 32174129, 14 March 2020

Available information on CT features of the 2019 novel coronavirus disease (COVID-19) is scattered in different publications, and a cohesive literature review has yet to be compiled. ...This systematic review of the current literature on COVID-19 provides insight into the initial and follow-up CT characteristics of the disease.