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The Virus

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31/07/2020 PERSPECTIVE
How does SARS-CoV-2 cause COVID-19?

SCIENCE

Authors
Nicholas J. Matheson, Paul J. Lehner



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24/07/2020 Articles
Structural basis of RNA cap modification by SARS-CoV-2

NATURE

Authors
Thiruselvam Viswanathan, Shailee Arya, Siu-Hong Chan, Shan Qi, Nan Dai, Anurag Misra, Jun-Gyu Park, Fatai Oladunni, Dmytro Kovalskyy, Robert A. Hromas, Luis Martinez-Sobrido, Yogesh K. Gupta



ABSTRACT
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions of infections worldwide. In SARS coronaviruses, the non-structural protein 16 (nsp16), in conjunction with nsp10, methylates the 5′-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of SARS-CoV-2 nsp16 and nsp10 in the presence of cognate RNA substrate analogue and methyl donor, S-adenosyl methionine (SAM). The nsp16/nsp10 heterodimer is captured in the act of 2′-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We observe large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This induced fit model provides mechanistic insights into the 2′-O methylation of the viral mRNA cap. We also discover a distant (25 Å) ligand-binding site unique to SARS-CoV-2, which can alternatively be targeted, in addition to RNA cap and SAM pockets, for antiviral development.

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24/07/2020 Communication
Presence of Genetic Variants Among Young Men With Severe COVID-19

JAMA

Authors
Caspar I. van der Made, Annet Simons, Janneke Schuurs-Hoeijmakers, Guus van den Heuvel, Tuomo Mantere, Simone Kersten, Rosanne C. van Deuren, Marloes Steehouwer, Simon V. van Reijmersdal, Martin Jaeger Tom Hofste, Galuh Astuti, Jordi Corominas Galbany, Vyne van der Schoot, Hans van der Hoeven, Wanda Hagmolen, Eva Klijn, Catrien van den Meer, Jeroen Fiddelaers, Quirijn de Mast, Chantal P. Bleeker-Rovers, Leo A. B. Joosten, Helger G. Yntema, Christian Gilissen, Marcel Nelen, Jos W. M. van der Meer, Han G. Brunner, Mihai G. Netea, Frank L. van de Veerdonk, Alexander Hoischen



ABSTRACT
Importance Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies that predispose to severe infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Objective To explore the presence of genetic variants associated with primary immunodeficiencies among young patients with COVID-19.
Design, Setting, and Participants Case series of pairs of brothers without medical history meeting the selection criteria of young (age <35 years) brother pairs admitted to the intensive care unit (ICU) due to severe COVID-19. Four men from 2 unrelated families were admitted to the ICUs of 4 hospitals in the Netherlands between March 23 and April 12, 2020. The final date of follow-up was May 16, 2020. Available family members were included for genetic variant segregation analysis and as controls for functional experiments.
Exposure Severe COVID-19.
Main Outcome and Measures Results of rapid clinical whole-exome sequencing, performed to identify a potential monogenic cause. Subsequently, basic genetic and immunological tests were performed in primary immune cells isolated from the patients and family members to characterize any immune defects.
Results The 4 male patients had a mean age of 26 years (range, 21-32), with no history of major chronic disease. They were previously well before developing respiratory insufficiency due to severe COVID-19, requiring mechanical ventilation in the ICU. The mean duration of ventilatory support was 10 days (range, 9-11); the mean duration of ICU stay was 13 days (range, 10-16). One patient died. Rapid clinical whole-exome sequencing of the patients and segregation in available family members identified loss-of-function variants of the X-chromosomal TLR7. In members of family 1, a maternally inherited 4-nucleotide deletion was identified (c.2129_2132del; p.[Gln710Argfs*18]); the affected members of family 2 carried a missense variant (c.2383G>T; p.[Val795Phe]). In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression of IRF7, IFNB1, and ISG15 on stimulation with the TLR7 agonist imiquimod as compared with family members and controls. The production of IFN-γ, a type II IFN, was decreased in patients in response to stimulation with imiquimod.
Conclusions and Relevance In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.

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24/07/2020 Viewpoint
Particle sizes of infectious aerosols: implications for infection cont...

Particle sizes of infectious aerosols: implications for infection control

THE LANCET

Authors
Kevin P Fennelly



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23/07/2020 Communication
HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across ...

HLA-B*44 and C*01 Prevalence Correlates with Covid19 Spreading across Italy

MDPI

Authors
Pierpaolo Correale, Luciano Mutti, Francesca Pentimalli, Giovanni Baglio, Rita Emilena Saladino,Pierpaolo Sileri, Antonio Giordano



ABSTRACT
The spread of COVID-19 is showing huge, unexplained, differences between northern and southern Italy. We hypothesized that the regional prevalence of specific class I human leukocyte antigen (HLA) alleles, which shape the anti-viral immune response, might partly underlie these differences. Through an ecological approach, we analyzed whether a set of HLA alleles (A, B, C), known to be involved in the immune response against infections, correlates with COVID-19 incidence. COVID-19 data were provided by the National Civil Protection Department, whereas HLA allele prevalence was retrieved through the Italian Bone-Marrow Donors Registry. Among all the alleles, HLA-A*25, B*08, B*44, B*15:01, B*51, C*01, and C*03 showed a positive log-linear correlation with COVID-19 incidence rate fixed on 9 April 2020 in proximity of the national outbreak peak (Pearson’s coefficients between 0.50 and 0.70, p-value < 0.0001), whereas HLA-B*14, B*18, and B*49 showed an inverse log-linear correlation (Pearson’s coefficients between −0.47 and −0.59, p-value < 0.0001). When alleles were examined simultaneously using a multiple regression model to control for confounding factors, HLA-B*44 and C*01 were still positively and independently associated with COVID-19: a growth rate of 16% (95%CI: 0.1–35%) per 1% point increase in B*44 prevalence; and of 19% (95%CI: 1–41%) per 1% point increase in C*01 prevalence. Our epidemiologic analysis, despite the limits of the ecological approach, is strongly suggestive of a permissive role of HLA-C*01 and B*44 towards SARS-CoV-2 infection, which warrants further investigation in case-control studies. This study opens a new potential avenue for the identification of sub-populations at risk, which could provide Health Services with a tool to define more targeted clinical management strategies and priorities in vaccination campaigns.

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23/07/2020 Report
Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

SCIENCE

Authors
Ching-Lin Hsieh, Jory A. Goldsmith, Jeffrey M. Schaub, Andrea M. DiVenere, Hung-Che Kuo, Kamyab Javanmardi, Kevin C. Le, Daniel Wrapp, Alison G. Lee, Yutong Liu, Chia-Wei Chou, Patrick O. Byrne, Christy K. Hjorth, Nicole V. Johnson, John Ludes-Meyers, Annalee W. Nguyen, Juyeon Park, Nianshuang Wang, Dzifa Amengor, Jason J. Lavinder, Gregory C. Ippolito, Jennifer A. Maynard2, Ilya J. Finkelstein, Jason S. McLellan



ABSTRACT
The COVID-19 pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. Here, we characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting ~10-fold higher expression than its parental construct and the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.

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22/07/2020 Articles
Potent neutralizing antibodies directed to multiple epitopes on SARS-C...

Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

NATURE

Authors
Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro, David D. Ho



ABSTRACT
The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

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21/07/2020 Articles
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in...

Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2

ASM JOURNALS

Authors
Yvonne C. F. Su, Danielle E. Anderson, Barnaby E. Young, Martin Linster, Feng Zhu, Jayanthi Jayakumar, Yan Zhuang, Shirin Kalimuddin, Jenny G. H. Low, Chee Wah Tan, Wan Ni Chia, Tze Minn Mak, Sophie Octavia, Jean-Marc Chavatte, Raphael T. C. Lee, Surinder Pada, Seow Yen Tan, Louisa Sun, Gabriel Z. Yan, Sebastian Maurer-Stroh, Ian H. Mendenhall, Yee-Sin Leo, David Chien Lye, Lin-Fa Wang, Gavin J. D. Smith



ABSTRACT
To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.

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17/07/2020 Articles
ACE2 gene variants may underlie interindividual variability and suscep...

ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population

NATURE

Authors
Elisa Benetti, Rossella Tita, Ottavia Spiga, Andrea Ciolfi, Giovanni Birolo, Alessandro Bruselles, Gabriella Doddato, Annarita Giliberti, Caterina Marconi, Francesco Musacchia, Tommaso Pippucci, Annalaura Torella, Alfonso Trezza, Floriana Valentino, Margherita Baldassarri, Alfredo Brusco, Rosanna Asselta, Mirella Bruttini, Simone Furini, Marco Seri, Vincenzo Nigro, Giuseppe Matullo, Marco Tartaglia, Francesca Mari, GEN-COVID Multicenter Study, Alessandra Renieri & Anna Maria Pinto



ABSTRACT
In December 2019, an initial cluster of interstitial bilateral pneumonia emerged in Wuhan, China. A human-to-human transmission was assumed and a previously unrecognized entity, termed coronavirus disease-19 (COVID-19) due to a novel coronavirus (SARS-CoV-2) was described. The infection has rapidly spread out all over the world and Italy has been the first European country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three more common missense changes, p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg) were predicted to interfere with protein structure and stabilization. Rare variants likely interfering with the internalization process, namely p.(Leu351Val) and p.(Pro389His), predicted to interfere with SARS-CoV-2 spike protein binding, were also observed. Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients. These findings suggest that a predisposing genetic background may contribute to the observed interindividual clinical variability associated with COVID-19, allowing an evidence-based risk assessment leading to personalized preventive measures and therapeutic options.

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10/07/2020 Reviews
Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus...

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

JAMA

Authors
W. Joost Wiersinga, Andrew Rhodes, Allen C. Cheng, Sharon J. Peacock, Hallie C. Prescott



ABSTRACT
Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

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09/07/2020 Articles
SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on viru...

SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects

NATURE

Authors
Antoni G. Wrobel, Donald J. Benton, Pengqi Xu, Chloë Roustan, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel, Steven J. Gamblin



ABSTRACT
SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.

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07/07/2020 Articles
SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental...

SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study

THE LANCET

Authors
Kore Schlottau, Melanie Rissmann, Annika Graaf, Jacob Schön, Julia Sehl, Claudia Wylezich, Dirk Höper, Thomas C Mettenleiter, Anne Balkema-Buschmann, Timm Harder, Christian Grund, Donata Hoffmann, Angele Breithaupt, Martin Beer


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07/07/2020 News
Covid-19: Airborne transmission is being underestimated, warn experts

THE BMJ

Authors
Owen Dyer


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06/07/2020 Articles
Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccin...

Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment

SCIENCE

Authors
Jing Sun, Zhen Zhuang, Jian Zheng, Paul B. McCray, Jr., Stanley Perlman, Jincun Zhao


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03/07/2020 Preview
Making sense of mutation: what D614G means for the COVID-19 pandemic r...

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

SCIENCE DIRECT

Authors
Nathan D. Grubaugh, William P. Hanage, Angela L. Rasmussen



ABSTRACT
Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

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02/07/2020 Reviews
Using heat to kill SARS‐CoV ‐2

WILEY ONLINE LIBRARY

Authors
John P. Abraham, Brian D. Plourde, Lijing Cheng


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01/07/2020 Articles
Coronaviruses and SARS-CoV-2: A Brief Overview

ANESTHESIA & ANALGESIA

Authors
Ludwig, Stephan, Zarbock, Alexander



ABSTRACT
In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of coronavirus disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.

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29/06/2020 Articles
Lower nasopharyngeal viral load during the latest phase of COVID-19 pa...

Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital

DE GRUYTER

Authors
Nicola Clementi, Roberto Ferrarese, Marco Tonelli, Virginia Amato, Sara Racca, Massimo Locatelli, Giuseppe Lippi, Guido Silvestri, Massimo Clementi, Nicasio Mancini



ABSTRACT
Objectives A milder clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been anecdotally reported over the latest phase of COVID-19 pandemic in Italy. Several factors may contribute to this observation, including the effect of lockdown, social distancing, lower humidity, lower air pollution, and potential changes in the intrinsic pathogenicity of the virus. In this regard, the clinical severity of COVID-19 could be attenuated by mutations in SARS-CoV-2 genome that decrease its virulence, as well as by lower virus inocula.
Methods In this pilot study, we compared the reverse transcription polymerase chain reaction (RT-PCR) amplification profile of 100 nasopharyngeal swabs consecutively collected in April, during the peak of SARS-CoV-2 epidemic, to that of 100 swabs collected using the same procedure in May.
Results The mean Ct value of positive samples collected in May was significantly higher than that of samples collected in the previous period (ORF 1a/b gene: 31.85 ± 0.32 vs. 28.37 ± 0.5, p<0.001; E gene: 33.76 ± 0.38 vs. 29.79 ± 0.63, p<0.001), suggesting a lower viral load at the time of sampling. No significant differences were observed between male and females in the two periods, whilst higher viral loads were found in (i) patients over 60-years old, and (ii) patients that experienced severe COVID-19 during the early stages of the pandemic.
Conclusions This pilot study prompts further investigation on the correlation between SARS-CoV-2 load and different clinical manifestation of COVID-19 during different phases of the pandemic. Laboratories should consider reporting quantitative viral load data in the molecular diagnosis of SARS-CoV-2 infection.

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23/06/2020 Reviews
The history and value of face masks

EUROPEAN MEDICAL OF RESEARCH

Authors
Christiane Matuschek, Friedrich Moll, Heiner Fangerau, Johannes C. Fischer, Kurt Zänker, Martijn van Griensven, Marion Schneider, Detlef Kindgen-Milles, Wolfram Trudo Knoefel, Artur Lichtenberg, Bálint Tamaskovics, Freddy Joel Djiepmo-Njanang, Wilfried Budach, Stefanie Corradini, Dieter Häussinger, Torsten Feldt, Björn Jensen, Rainer Pelka, Klaus Orth, Matthias Peiper, Olaf Grebe, Kitti Maas, Edwin Bölke, Jan Haussmann



ABSTRACT
In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.

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22/06/2020 News
Mini organs reveal how the coronavirus ravages the body

NATURE

Authors
Smriti Mallapaty


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22/06/2020 News
Going back in time for an antibody to fight COVID-19

NATURE

Authors
Gary R. Whittaker, Susan Daniel


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18/06/2020 Articles
The receptor binding domain of the viral spike protein is an immunodom...

The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients

SCIENCE

Authors
Lakshmanane Premkumar, Bruno Segovia-Chumbez , Ramesh Jadi, David R. Martinez, Rajendra Raut, Alena Markmann, Caleb Cornaby, Luther Bartelt, Susan Weiss, Yara Park, Caitlin E. Edwards, Eric Weimer, Erin M. Scherer, Nadine Rouphael, Srilatha Edupuganti, Daniela Weiskopf, Longping V. Ts, Yixuan J. Hou, David Margolis, Alessandro Sette, Matthew H. Collins, John Schmitz, Ralph S. Baric, Aravinda M. de Silva



ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.

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18/06/2020 Letter
Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in...

Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Pets in Wuhan, China

Authors
Jianjun Chen , Chaolin Huang , Yanan Zhang , Sai Zhang , Meilin Jin


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17/06/2020 Articles
Evidence for host-dependent RNA editing in the transcriptome of SARS-C...

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2

SCIENCE

Authors
Salvatore DiGiorgio, Filippo Martignano, Maria Gabriella Torcia, Giorgio Mattiuz, Silvestro G. Conticello



ABSTRACT
The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.

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17/06/2020 Articles
Genomewide Association Study of Severe Covid-19 with Respiratory Failu...

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
The Severe Covid-19 GWAS Group



ABSTRACT
BACKGROUND
There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.
METHODS We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality con- trol and the exclusion of population outliers, 835 patients and 1255 control par- ticipants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels.
RESULTS We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10−8) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10−10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10−8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5).
CONCLUSIONS We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.)


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17/06/2020 Reviews
Vaccines against Coronaviruses: The State of the Art

MDPI

Authors
Cristiano Conte, Francesco Sogni , Paola Affanni , Licia Veronesi , Alberto Argentiero, Susanna Esposito



ABSTRACT
The emerging epidemic caused by the new coronavirus SARS-CoV-2 represents the most important socio-health threat of the 21st century. The high contagiousness of the virus, the strong impact on the health system of the various countries and the absence to date of treatments able to improve the prognosis of the disease make the introduction of a vaccine indispensable, even though there are currently no approved human coronavirus vaccines. The aim of the study is to carry out a review of the medical literature concerning vaccine candidates for the main coronaviruses responsible for human epidemics, including recent advances in the development of a vaccine against COVID-19. This extensive review carried out on the vaccine candidates of the main epidemic coronaviruses of the past has shown that the studies in animal models suggest a high efficacy of potential vaccines in providing protection against viral challenges. Similar human studies have not yet been carried out, as the main trials are aimed at assessing mainly vaccine safety and immunogenicity. Whereas the severe acute respiratory syndrome (SARS-CoV) epidemic ended almost two decades ago and the Middle East respiratory syndrome (MERS-CoV) epidemic is now better controlled, as it is less contagious due to the high lethality of the virus, the current SARS-CoV-2 pandemic represents a problem that is certainly more compelling, which pushes us to accelerate the studies not only for the production of vaccines but also for innovative pharmacological treatments. SARS-CoV-2 vaccines might come too late to affect the first wave of this pandemic, but they might be useful if additional subsequent waves occur or in a post-pandemic perspective in which the virus continues to circulate as a seasonal virus.

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16/06/2020 Primer
Respiratory Virus Infections: Understanding COVID-19

SCIENCE DIRECT

Authors
Kanta Subbarao, Siddhartha Mahanty



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04/06/2020 Viewpoint
Responding to the COVID-19 Pandemic The Need for a Structurally Compet...

Responding to the COVID-19 Pandemic The Need for a Structurally Competent Health Care System

JAMA

Authors
Jonathan M. Metzl, Aletha Maybank; Fernando De Maio

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03/06/2020 Short Communication
Evidence for mutations in SARS-CoV-2 Italian isolates potentially affe...

Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission

JOURNAL OF MEDICAL VIROLOGY

Authors
Domenico Benvenuto Ayse Banu Demir Marta Giovanetti Martina Bianchi Silvia Angeletti Stefano Pascarella Roberto Cauda Massimo Ciccozzi Antonio Cassone

ABSTRACT Italy is the first western country suffering heavy SARS‐CoV‐2 transmission and disease impact after Covid‐19 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS‐CoV‐2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three non‐synonimous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bio‐informatic tools. Amino acid analysis and changes in three‐dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favour virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.

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27/05/2020 Comment
Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 tran...

Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission

The Lancet

Authors
G Aernout Somsen, Cees van Rijn, Stefan Kooij, Reinout A Bem, Daniel Bonn

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20/05/2020 Article
How to Discover Antiviral Drugs Quickly

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Jerry M. Parks, Jeremy C. Smith

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19/05/2020 Advanced Research
COVID-19 infection: Origin, transmission, and characteristics of human...

COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

Science Direct

Authors
Muhammad AdnanShereen, Suliman Khana, AbeerKazmic, NadiaBashira, Rabeea Siddique

ABSTRACT

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.

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18/05/2020 Research Article
Evidence for host-dependent RNA editing in the transcriptome of SARS-C...

Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2 in humans

SCIENCE

Authors
Salvatore Di Giorgio, Filippo Martignano, Maria Gabriella Torcia, Giorgio Mattiuz, Silvestro G. Conticello

ABSTRACT

The COVID-19 outbreak has become a global health risk and understanding the response of the host to the SARS-CoV-2 virus will help to contrast the disease. Editing by host deaminases is an innate restriction process to counter viruses, and it is not yet known whether it operates against Coronaviruses. Here we analyze RNA sequences from bronchoalveolar lavage fluids derived from infected patients. We identify nucleotide changes that may be signatures of RNA editing: Adenosine-to-Inosine changes from ADAR deaminases and Cytosine-to-Uracil changes from APOBEC ones. A mutational analysis of genomes from different strains of human-hosted Coronaviridae reveals mutational patterns compatible to those observed in the transcriptomic data. Our results thus suggest that both APOBECs and ADARs are involved in Coronavirus genome editing, a process that may shape the fate of both virus and patient.

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18/05/2020 Arts and Culture
How to Draw the Coronavirus

THE PARIS REVIEW

Authors
Rebekah Frumkin

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14/05/2020 Opinion
No evidence for distinct types in the evolution of SARS-CoV-2

OXFORD ACADEMY

Authors
Oscar A. MacLean, Richard J. Orton, Joshua B. Singer, David L. Robertson

ABSTRACT

A recent study by Tang et al. claimed that two major types of severe acute respiratory syndrome-coronavirus-2 (CoV-2) had evolved in the ongoing CoV disease-2019 pandemic and that one of these types was more ‘aggressive’ than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al., and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks, we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.

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11/05/2020 Report
A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural...

A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions...

SCIENCE DIRECT

Authors
Hong Zhou, Xing Chen, Tao Hu, Juan Li, Hao Song, Yanran Liu, Peihan Wang, Di Liu, Jing Yang, Edward C. Holmes, Alice C. Hughes, Yuhai Bi, Weifeng Shi

ABSTRACT The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.

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08/05/2020 Report
A highly conserved cryptic epitope in the receptor binding domains of ...

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2...

SCIENCE

Authors
Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Ray T. Y. So, Huibin Lv, Chris K. P. Mok, Ian A. Wilson

ABSTRACT

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.

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07/05/2020 Link
Genomic epidemiology of novel coronavirus - Global subsampling

NEXSTRAIN

Authors
NEXSTRAIN

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04/05/2020 News
Profile of a killer the complex biology powering the coronavirus pande...

Profile of a killer the complex biology powering the coronavirus pandemic

Nature

Authors
David Cyranoski

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04/05/2020 Report
Inquinamento atmosferico e diffusione del virus SARS-CoV-2

ISTITUTO SUPERIORE DI SANITA'

Authors
ISTITUTO SUPERIORE DI SANITA'


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01/05/2020 Articles
SARS-CoV-2 productively infects human gut enterocytes

Science

Authors
Mart M. Lamers, Joep Beumer, Jelte van der Vaart,, Kèvin Knoops, Jens Puschhof, Tim I. Breugem1, Raimond B. G. Ravelli, J. Paul van Schayck, Anna Z. Mykytyn, Hans Q. Duimel, Elly van Donselaar, Samra Riesebosch, Helma J. H. Kuijpers, Debby Schippers, Willine J. van de Wetering, Miranda de Graaf, Marion Koopmans, Edwin Cuppen, Peter J. Peters, Bart L. Haagmans, Hans Clevers

ABSTRACT


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


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29/04/2020 New Result
Spike mutation pipeline reveals the emergence of a more transmissible ...

Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2

bioRxiv

Authors
Werner Abfalterer, Brian Foley, Elena E Giorgi, Tanmoy Bhattacharya, Matthew D Parker, David G Partridge, Cariad M Evans,Thushan de Silva, Celia C LaBranche, David C Montefiori

Abstract

We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.

Read More »

21/04/2020 Articles
Comparative tropism, replication kinetics, and cell damage profiling o...

Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV...

The Lancet

Authors
Hin Chu, Jasper Fuk-Woo Chan, Terrence Tsz-Tai Yuen, Huiping Shuai, Shuofeng Yuan, Yixin Wang, Bingjie Hu, Cyril Chik-Yan Yip, Jessica Oi-Ling Tsang, Xiner Huang, Yue Chai, Dong Yang, Yuxin Hou, Kenn Ka-Heng Chik, Xi Zhang, Agnes Yim-Fong Fung, Hoi-Wah Tsoi, Jian-Piao Cai, Wan-Mui Chan, Jonathan Daniel Ip, Allen Wing-Ho Chu, Jie Zhou, David Christopher Lung, Kin-Hang Kok, Kelvin Kai-Wang To, Owen Tak-Yin Tsang, Kwok-Hung Chan, Kwok-Yung Yuen

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21/04/2020 Comment
SARS-CoV-2 cellular tropism

The Lancet

Authors
VALERIA CAGNO

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19/04/2020 Abstract
Recent progress and challenges in drug development against COVID-19...

NCBI

Authors
Tarek Mohamed Abd El-Aziza, James D. Stockanda

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18/04/2020 World Report
Flooded by the torrent: the COVID-19 drug pipeline

The Lancet

Authors
Asher Mullard

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17/04/2020 Letter
SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19...

SARS-CoV-2 Isolation From Ocular Secretions of a Patient With COVID-19 in Italy...

ANNALS OF INTERNAL MEDICINE

Authors
Francesca Colavita, Daniele Lapa, Fabrizio Carletti, Eleonora Lalle, Licia Bordi, Patrizia Marsella, Emanuele Nicastri, Nazario Bevilacqua, Maria Letizia Giancola, Angela Corpolongo, Giuseppe Ippolito, Maria Rosaria Capobianchi, Concetta Castilletti,

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16/04/2020 Articles
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a ...

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

SCIENCE DIRECT

Authors
Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder, Nadine Kruger, Tanja Herrler, Sandra Erichsen, Tobias S. Schiergens, Georg Herrler, Nai-Huei Wu, Andreas Nitsche, Marcel A. Muller, Christian Drosten and Stefan Pohlmann

Summary 

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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16/04/2020 News
Covid-19: First coronavirus was described in The BMJ in 1965

THE BMJ

Authors
Elisabeth Mahase

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16/04/2020 Correspondence
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-...

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Neeltje van Doremalen, Trenton Bushmaker, Dylan H. Morris, Myndi G. Holbrook, Amandine Gamble, Brandi N. Williamson, Azaibi Tamin, Jennifer L. Harcourt, Natalie J. Thornburg, Susan I. Gerber, James O. Lloyd-Smith, Emmie de Wit, Vincent J. Munster

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15/04/2020 Correspondence
Droplets and Aerosols in the Transmission of SARS-CoV-2

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Matthew Meselson

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15/04/2020 Communication
Temporal dynamics in viral shedding and transmissibility of COVID-19

NATURE MEDICINE

Authors
Xi He, Eric H. Y. Lau, Peng Wu, Xilong Deng, Jian Wang, Xinxin Hao, Yiu Chung Lau ,Jessica Y. Wong, Yujuan Guan, Xinghua Tan, Xiaoneng Mo, Yanqing Chen, Baolin Liao, Weilie Chen, Fengyu Hu, Qing Zhang, Mingqiu Zhong, Yanrong Wu, Lingzhai Zhao, Fuchun Zhang, Benjamin J. Cowling, Fang Li and Gabriel M. Leung

ABSTRACT

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.

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10/04/2020 Report
Structure of the RNA-dependent RNA polymerase from COVID-19 virus

SCIENCE

Authors
Yan Gao, Liming Yan,Yucen Huang, Fengjiang Liu, Yao Zhao, Lin Cao, Tao Wang, Qianqian Sun,Zhenhua Ming, Lianqi Zhang, Ji Ge, Litao Zheng, Ying Zhan, Haofeng Wang, Yan Zhu,Chen Zhu,Tianyu Hu, Tian Hua, Bing Zhang, Xiuna Yang, Jun Li, Haitao Yang, Zhijie Liu, Wenqing Xu, Luke W.Guddat, Quan Wang, Zhiyong Lou, Zihe Rao

ABSTRACT 

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 full-length 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 β-hairpin 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.

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09/04/2020 Articles
Structure of Mpro from COVID-19 virus and discovery of its inhibitors

CSH LABORATORY

Authors
Zhenming Jin, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, Xiaofeng Li, Leike Zhang, Chao Peng, Yinkai Duan, Jing Yu, Lin Wang, Kailin Yang, Fengjiang Liu, Rendi Jiang, Xinglou Yang, Tian You, Xiaoce Liu, Xiuna Yang, Fang Bai, Hong Liu, Xiang Liu, Luke W. Guddat, Wenqing Xu, Gengfu Xiao, Chengfeng Qin, Zhengli Shi, Hualiang Jiang, Zihe Rao &amp; Haitao Yang

Abstract

A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1-4. Currently there is no targeted therapeutics and effective 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 identified 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 inhibit Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited strong antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.

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08/04/2020 New Result
Genomic determinants of pathogenicity in SARS-CoV-2 and other human co...

Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses

BIORXIV

Authors
Ayal B. Gussow, Noam Auslander, Yuri I. Wolf, Eugene V. Koonin



ABSTRACT
SARS-CoV-2 poses an immediate, urgent and major threat to public health across the globe. Here we report an in-depth molecular analysis to reconstruct the evolutionary origins of the enhanced pathogenicity of SARS-CoV-2 and other coronaviruses that are severe human pathogens. Using integrated comparative genomics and machine learning techniques, we identify key genomic features that differentiate SARS-CoV-2 and the viruses behind the two previous coronavirus outbreaks, SARS-CoV and MERS-CoV, from less pathogenic coronaviruses. The identified features could be crucial elements of coronavirus pathogenicity and possible targets for diagnostics, prognostication and interventions.

Read More »

08/04/2020 Articles
Phylogenetic network analysis of SARS-CoV-2 genomes

PNAS

Authors
Peter Forstera, Lucy Forsterd, Colin Renfrewb, Michael Forsterc

Summary

 In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide. 

Read More »

02/04/2020 Communication
Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isola...

Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy...

Eurosurveillance

Authors
Paola Stefanelli , Giovanni Faggioni , Alessandra Lo Presti , Stefano Fiore , Antonella MarchI , Eleonora BenedettI , Concetta FabianI , Anna Anselmo, Andrea Ciammaruconi , Antonella Fortunato , Riccardo De Santis, Silvia Fillo, MariaRosaria Capobianchi , Maria Rita Gismondo , Alessandra Ciervo , Giovanni Rezza , Maria Rita Castrucci , Florigio Lista , on behalf of ISS COVID-19 study group6

Abstract
Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient’s sequence clustered with sequences from Germany while the tourist’s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients’ sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.

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30/03/2020 Articles
Estimates of the severity of coronavirus disease 2019: a model-based a...

Estimates of the severity of coronavirus disease 2019: a model-based analysis

The Lancet

Authors
Robert Verity, Lucy C Okell, Ilaria Dorigatti*, Peter Winskill, Charles Whittaker, Natsuko Imai, Gina Cuomo-Dannenburg, Hayley Thompson, Patrick G T Walker, Han Fu, Amy Dighe, Jamie T Griffin, Marc Baguelin, Sangeeta Bhatia, Adhiratha Boonyasiri, Anne Cori, Zulma Cucunub&aacute;, Rich FitzJohn, Katy Gaythorpe, Will Green, Arran Hamlet, Wes Hinsley, Daniel Laydon, Gemma Nedjati-Gilani, Steven Riley, Sabine van Elsland, Erik Volz, Haowei Wang, Yuanrong Wang, Xiaoyue Xi, Christl A Donnelly, Azra C Ghani, Neil M Ferguson

ABSTRACT

Background

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.

Findings

Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older.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 hospitalisation.

Interpretation

These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death.

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30/03/2020 Comment
Likelihood of survival of coronavirus disease 2019

The Lancet

Authors
Shigui Ruan

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30/03/2020 Articles
Estimating the number of infections and the impact of non-pharmaceutic...

Estimating the number of infections and the impact of non-pharmaceutical interventions....

Imperial College London

Authors
Seth Flaxman, , Swapnil Mishra, Axel Gandy, H Juliette T Unwin, Helen Coupland, Thomas A Mellan, Harrison Zhu, Tresnia Berah, Jeffrey W Eaton, Pablo N P Guzman, Nora Schmit, Lucia Cilloni, Kylie E C Ainslie, Marc Baguelin, Isobel Blake, Adhiratha Boonyasiri, Olivia Boyd, Lorenzo Cattarino, Constanze Ciavarella, Laura Cooper, Zulma Cucunub&aacute;, Gina Cuomo-Dannenburg, Amy Dighe, Bimandra Djaafara, Ilaria Dorigatti, Sabine van Elsland, Rich FitzJohn, Han Fu, Katy Gaythorpe, Lily Geidelberg, Nicholas Grassly, Will Green, Timothy Hallett, Arran Hamlet, Wes Hinsley, Ben Jeffrey, David Jorgensen, Edward Knock, Daniel Laydon, Gemma Nedjati-Gilani, Pierre Nouvellet, Kris Parag, Igor Siveroni, Hayley Thompson, Robert Verity, Erik Volz, Caroline Walters, Haowei Wang, Yuanrong Wang, Oliver Watson, Peter Winskill, Xiaoyue Xi, Charles Whittaker, Patrick GT Walker, Azra Ghani, Christl A. Donnelly, Steven Riley, Lucy C Okell, Michaela A C Vollmer, Neil M. Ferguson1 and Samir Bhatt

ABSTRACT

Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproduction number may be above or below this value. With current interventions remaining in place to at least the end of March, we estimate that interventions across all 11 countries will have averted 59,000 deaths up to 31 March [95% credible interval 21,000-120,000]. Many more deaths will be averted through ensuring that interventions remain in place until transmission drops to low levels. We estimate that, across all 11 countries between 7 and 43 million individuals have been infected with SARS-CoV-2 up to 28th March, representing between 1.88% and 11.43% of the population. The proportion of the population infected to date – the attack rate - is estimated to be highest in Spain followed by Italy and lowest in Germany and Norway, reflecting the relative stages of the epidemics. Given the lag of 2-3 weeks between when transmission changes occur and when their impact can be observed in trends in mortality, for most of the countries considered here it remains too early to be certain that recent interventions have been effective. If interventions in countries at earlier stages of their epidemic, such as Germany or the UK, are more or less effective than they were in the countries with advanced epidemics, on which our estimates are largely based, or if interventions have improved or worsened over time, then our estimates of the reproduction number and deaths averted would change accordingly. It is therefore critical that the current interventions remain in place and trends in cases and deaths are closely monitored in the coming days and weeks to provide reassurance that transmission of SARS-Cov-2 is slowing

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28/03/2020 Editorial
Covid-19 — Navigating the Uncharted

The New Egland Journal of Medicine

Authors
Anthony S. Fauci, Clifford Lane, Robert R. Redfield

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25/03/2020 Correspondence
Coordination of RECOVERY, RECOVERY-RS and PRINCIPLE trials

REMAP-CAP

Authors
REMAP-CAP

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25/03/2020 Overview
2019 Novel coronavirus (COVID-19) overview

SPRINGER LINK

Authors
Mehrdad Mohammadi, Maryam Meskini, Anderia Lucia do Nascimento Pinto

Abstract
Novel coronaviruses (CoVs) are zoonotic pathogens, but the first human-to-human transmission has been reported. CoVs have the best known genome of all RNA viruses, and mutations in the genome have now been found. A pneumonia of unknown cause detected in Wuhan, China, was first reported to the WHO Country Office in China on 31 December 2019. This study aims to report early findings related to COVID-19 and provide methods to prevent and treat it.

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23/03/2020 Viewpoint
Case-Fatality Rate and Characteristics of Patients Dying in Relation t...

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

JAMA

Authors
Graziano Onder, Giovanni Rezza, Silvio Brusaferro

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19/03/2020 Articles
Characterization of the receptor-binding domain (RBD) of 2019 novel co...

Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for...

Springer Nature

Authors
Wanbo Tai, Lei He, Xiujuan Zhang, Jing Pu, Denis Voronin, Shibo Jiang, Yusen Zhou, Lanying Du

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). 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.

2019 novel coronavirus, SARS-CoV-2, spike protein, receptor-binding domain, viral inhibitor, cross-neutralization

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17/03/2020 Correspondence
The proximal origin of SARS-CoV-2

Springer Nature

Authors
Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, Robert F. Garry

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09/03/2020 Articles
Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients

Oxford Academy

Authors
Zijie Shen, Yan Xiao, Lu Kang, Wentai Ma, Leisheng Shi, Li Zhang, Zhuo Zhou, Jing Yang, Jiaxin Zhong, Donghong Yang, Li Guo, Guoliang Zhang, Hongru Li, Yu Xu, Mingwei Chen, Zhancheng Gao, Jianwei Wang , Lili Ren, Mingkun Li

Background
A novel coronavirus (SARS-CoV-2) has infected more than 75,000 individuals and spread to over 20 countries. It is still unclear how fast the virus evolved and how the virus interacts with other microorganisms in the lung.

Methods
We have conducted metatranscriptome sequencing for the bronchoalveolar lavage fluid of eight SARS-CoV-2 patients, 25 community-acquired pneumonia (CAP) patients, and 20 healthy controls.

Results
The median number of intra-host variants was 1-4 in SARS-CoV-2 infected patients, which ranged between 0 and 51 in different samples. The distribution of variants on genes was similar to those observed in the population data (110 sequences). However, very few intra-host variants were observed in the population as polymorphism, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intra-host variants in a person-to-person spread, the risk should not be overlooked. The microbiota in SARS-CoV-2 infected patients was similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria.

Conclusion
SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intra-host variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

SARS-CoV-2, COVID-19, intra-host variant, microbiota, transmission

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05/03/2020 Correspondence
A distinct name is needed for the new coronavirus

The Lancet

Authors
Shibo Jiang, Zhengli Shi, Yuelong Shu, Jingdong Song, George F Gao, Wenjie Tan, Deyin Guo

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01/03/2020 Correspondence
Coordination of recovery and remap cap

REMAP-CAP

Authors
REMAP-CAP

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25/02/2020 Short Communication
Early phylogenetic estimate of the effective reproduction number of SA...

Early phylogenetic estimate of the effective reproduction number of SARS‐CoV‐2

Wiley Online Library

Authors
Alessia Lai, Annalisa Bergna, Carla Acciarri, Massimo Galli, Gianguglielmo Zehender

To reconstruct the evolutionary dynamics of the 2019 novel‐coronavirus recently causing an outbreak in Wuhan, China, 52 SARS‐CoV‐2 genomes available on 4 February 2020 at Global Initiative on Sharing All Influenza Data were analyzed. The two models used to estimate the reproduction number (coalescent‐based exponential growth and a birth‐death skyline method) indicated an estimated mean evolutionary rate of 7.8 × 10−4 subs/site/year (range, 1.1 × 10−4‐15 × 10−4) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range, 2.1‐5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.

evolutionary dynamics, reproductive number, SARS‐CoV‐2

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24/02/2020 Articles
Functional assessment of cell entry and receptor usage for SARS-CoV-2....

Functional assessment of cell entry and receptor usage for SARS-CoV-2....

Nature Research

Authors
Michael Letko, Andrea Marzi, Vincent Munster

Abstract

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoo- notic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.

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19/02/2020 Viewpoint
Defining the Epidemiology of Covid-19 — Studies Needed

The NEW ENGLAND JOURNAL of MEDICINE

Authors
Marc Lipsitch, D.Phil., David L. Swerdlow, and Lyn Finelli

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19/02/2020 Letter
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patie...

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Lirong Zou, et all

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19/02/2020 Editorial
Coronaviruses in animals and humans

The bmj

Authors
Lisa F P Ng, Julian A Hiscox

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18/02/2020 Reviews
2019 Novel coronavirus: where we are and what we know

SPRINGER LINK

Authors
Zhangkai J. Cheng, Jing Shan



ABSTRACT
There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.

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13/02/2020 Articles
No credible evidence supporting claims of the

Taylor and Francis Group

Authors
Shan-Lu Liu, Linda J. Saif, Susan R. Weiss &amp; Lishan Su

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03/02/2020 Articles
A pneumonia outbreak associated with a new coronavirus of probable bat...

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Nature

Authors
Peng Zhou, Xing-Lou Yang, Xian-Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao-Rui Si, Yan Zhu, Bei Li, Chao-Lin Huang, Hui-Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren-Di Jiang, Mei-Qin Liu, Ying Chen, Xu-Rui Shen, Xi Wang, Xiao-Shuang Zheng, Kai Zhao, Quan-Jiao Chen, Fei Deng, Lin-Lin Liu, Bing Yan, Fa-Xian Zhan, Yan-Yi Wang, Geng-Fu Xiao, Zheng-Li Shi

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4
Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7
Here we report the identifcation and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confrmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from fve patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fuid of a critically ill patient could be neutralized by sera from several patients. Notably, we confrmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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30/01/2020 Articles
Genomic characterisation and epidemiology of 2019 novel coronavirus: i...

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

The Lancet

Authors
Prof Roujian Lu, Xiang Zhao, Juan Li, Peihua Niu, Bo Yang, Honglong Wu, Wenling Wang, Hao Song, Baoying Huang, Na Zhu, Yuhai Bi, Xuejun Ma, Prof Faxian Zhan, Liang Wang, Tao Hu, Hong Zhou, Prof Zhenhong Hu, Prof Weimin Zhou, Li Zhao, Jing Chen, Yao Meng, Ji Wang, Yang Lin, Jianying Yuan, Zhihao Xie, Jinmin Ma, William J Liu, Dayan Wang,Prof Wenbo Xu, Edward C Holmes, George F Gao, Guizhen Wu

Summary
Background
In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. 

Methods
We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus.

Findings
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. 

Funding
National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

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10/12/2018 Reviews
Origin and evolution of pathogenic coronaviruses

Nature Reviews

Authors
Jie Cui, Fang Li, Zheng-Li Shi

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

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