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22/08/2022 Original Investigation
Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains A Sy...

Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains A Systematic Review and Meta-analysis

JAMA

Authors
Yu Wu, PhD; Liangyu Kang, MD; Zirui Guo, MD; Jue Liu, PhD; Min Liu, PhD; Wannian Liang

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01/08/2022 Articles
Intrinsic generation time of the SARS-CoV-2 Omicron variant: An observ...

Intrinsic generation time of the SARS-CoV-2 Omicron variant: An observational study of household transmission

THE LANCET

Authors
Mattia Manica 1 Alfredo De Bellis 1 Giorgio Guzzetta 1 Pamela Mancuso Massimo Vicentini Francesco Venturelli Alessandro Zerbini Eufemia Bisaccia Maria Litvinova Francesco Menegale Carla Molina Grané Piero Poletti Valentina Marziano Agnese Zardini Valeria d'Andrea Filippo Trentini Antonino Bella Flavia Riccardo Patrizio Pezzotti Marco Ajelli Paolo Giorgi Rossi Stefano Merler

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08/07/2022 Articles
Effectiveness and protection duration of Covid-19 vaccines and previou...

Effectiveness and protection duration of Covid-19 vaccines and previous infection against any SARS-CoV-2 infection in young adults

NATURE

Authors
Lior Rennert, Zichen Ma, Christopher S. McMahan, Delphine Dean

Abstract
Data on effectiveness and protection duration of Covid-19 vaccines and previous infection against general SARS-CoV-2 infection in general populations are limited. Here we evaluate protection from Covid-19 vaccination (primary series) and previous infection in 21,261 university students undergoing repeated surveillance testing between 8/8/2021–12/04/2021, during which B.1.617 (delta) was the dominant SARS-CoV-2 variant. Estimated mRNA-1273, BNT162b2, and AD26.COV2.S effectiveness against any SARS-CoV-2 infection is 75.4% (95% CI: 70.5-79.5), 65.7% (95% CI: 61.1-69.8), and 42.8% (95% CI: 26.1–55.8), respectively. Among previously infected individuals, protection is 72.9% when unvaccinated (95% CI: 66.1–78.4) and increased by 22.1% with full vaccination (95% CI: 15.8–28.7). Statistically significant decline in protection is observed for mRNA-1273 (P < .001), BNT162b2 (P < .001), but not Ad26.CoV2.S (P = 0.40) or previous infection (P = 0.12). mRNA vaccine protection dropped 29.7% (95% CI: 17.9–41.6) six months post- vaccination, from 83.2% to 53.5%. We conclude that the 2-dose mRNA vaccine series initially offers strong protection against general SARS-CoV-2 infection caused by the delta variant in young adults, but protection substantially decreases over time. These findings indicate that vaccinated individuals may still contribute to community spread. While previous SARS-CoV-2 infection consistently provides moderately strong protection against repeat infection from delta, vaccination yields a substantial increase in protection.

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06/07/2022 Original Investigation
Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths ...

Estimated Number of COVID-19 Infections, Hospitalizations, and Deaths Prevented Among Vaccinated Persons in the US, December 2020 to September 2021

JAMA

Authors
Molly K. Steele, Alexia Couture, Carrie Reed, Danielle Iuliano, Michael Whitaker, Hannah Fast, Aron J. Hall, Adam MacNeil, Betsy Cadwell, Kristin J. Marks, Benjamin J. Silk

Abstract
Importance The number of SARS-CoV-2 infections and COVID-19–associated hospitalizations and deaths prevented among vaccinated persons, independent of the effect of reduced transmission, is a key measure of vaccine impact.

Objective To estimate the number of SARS-CoV-2 infections and COVID-19–associated hospitalizations and deaths prevented among vaccinated adults in the US.

Design, Setting, and Participants In this modeling study, a multiplier model was used to extrapolate the number of SARS-CoV-2 infections and COVID-19–associated deaths from data on the number of COVID-19–associated hospitalizations stratified by state, month, and age group (18-49, 50-64, and ≥65 years) in the US from December 1, 2020, to September 30, 2021. These estimates were combined with data on vaccine coverage and effectiveness to estimate the risks of infections, hospitalizations, and deaths. Risks were applied to the US population 18 years or older to estimate the expected burden in that population without vaccination. The estimated burden in the US population 18 years or older given observed levels of vaccination was subtracted from the expected burden in the US population 18 years or older without vaccination (ie, counterfactual) to estimate the impact of vaccination among vaccinated persons.

Exposures Completion of the COVID-19 vaccination course, defined as 2 doses of messenger RNA (BNT162b2 or mRNA-1273) vaccines or 1 dose of JNJ-78436735 vaccine.

Main Outcomes and Measures Monthly numbers and percentages of SARS-CoV-2 infections and COVID-19–associated hospitalizations and deaths prevented were estimated among those who have been vaccinated in the US.

Results COVID-19 vaccination was estimated to prevent approximately 27 million (95% uncertainty interval [UI], 22 million to 34 million) infections, 1.6 million (95% UI, 1.4 million to 1.8 million) hospitalizations, and 235 000 (95% UI, 175 000–305 000) deaths in the US from December 1, 2020, to September 30, 2021, among vaccinated adults 18 years or older. From September 1 to September 30, 2021, vaccination was estimated to prevent 52% (95% UI, 45%–62%) of expected infections, 56% (95% UI, 52%-62%) of expected hospitalizations, and 58% (95% UI, 53%-63%) of expected deaths in adults 18 years or older.

Conclusions and Relevance These findings indicate that the US COVID-19 vaccination program prevented a substantial burden of morbidity and mortality through direct protection of vaccinated individuals.

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30/06/2022 Articles
Characteristics associated with the residual risk of severe COVID-19 a...

Characteristics associated with the residual risk of severe COVID-19 after a complete vaccination schedule: A cohort study of 28 million people in France

THE LANCET

Authors
Laura Semenzato Jérémie Botton Jérôme Drouin Bérangère Baricault Marion Bertrand Marie-Joëlle Jabagi François Cuenot Stéphane Le Vu Rosemary Dray-Spira Alain Weill Mahmoud Zureik

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23/06/2022 Report
Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2...

Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct

SCIENCE

Authors
Anna Z. Mykytyn1 , Melanie Rissmann1 †, Adinda Kok1 †, Miruna E. Rosu1 †, Debby Schipper1 , Tim I. Breugem1 , Petra B. van den Doel1 , Felicity Chandler1 , Theo Bestebroer1 , Maurice de Wit2, Martin E. van Royen3, Richard Molenkamp1 , Bas B. Oude Munnink1 , Rory D. de Vries1 , Corine GeurtsvanKessel, Derek J. Smith, Marion P. G. Koopmans, Barry Rockx, Mart M. Lamers, Ron Fouchier, Bart L. Haagmans

Abstract
The emergence and rapid spread of SARS-CoV-2 variants may impact vaccine efficacy significantly. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early SARS-CoV-2 variants (614G, Alpha, Beta, Gamma, Zeta, Delta and Mu) using hamster antisera obtained after primary infection. We first verified that the choice of the cell line for the neutralization assay did not affect the topology of the map substantially. Antigenic maps generated using pseudotyped SARS-CoV-2 on the widely used VeroE6 cell line and the human airway cell line Calu-3 generated similar maps. Maps made using authentic SARS-CoV-2 on Calu-3 cells also closely resembled those generated with pseudotyped viruses. The antigenic maps revealed a central cluster of SARS-CoV-2 variants, which grouped based on mutual spike mutations. Whereas these early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape vaccine-induced antibody responses as a result of different antigenic characteristics. Thus, antigenic cartography could be used to assess antigenic properties of future SARS-CoV-2 variants of concern that emerge and to decide on the composition of novel spike-based (booster) vaccines.

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17/06/2022 News
Covid-19: Long covid risk is lower with omicron than delta, researcher...

Covid-19: Long covid risk is lower with omicron than delta, researchers find

THE BMJ

Authors
Jacqui Wise

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24/05/2022 Articles
Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England

SCIENCE

Authors
Paul Elliott, Oliver Eales, Nicholas Steyn, David Tang, Barbara Bodinier, Haowei Wang, Joshua Elliott, Matthew Whitaker, Christina Atchison, Peter J. Diggle, Andrew J. Page, Alexander J. Trotter, Deborah Ashby, Wendy Barclay, Graham Taylor, Helen Ward, Ara Darzi, Graham S. Cooke, Christl A. Donnelly, Marc Chadeau-Hyam

Abstract
Rapid transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The REal-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5+ years, approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (N=109,181) with Omicron BA.2 largely replacing BA.1. Prevalence was increasing overall with the greatest increase in those aged 65-74 and 75+ years. This was associated with increased hospitalizations and deaths but at much lower levels than in previous waves against a backdrop of high levels of vaccination.

07/04/2022 News
Covid-19: Symptomatic infection with omicron variant is milder and sho...

Covid-19: Symptomatic infection with omicron variant is milder and shorter than with delta, study reports

THE BMJ

Authors
Jacqui Wise

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04/03/2022 Articles
Evolution of the SARS-CoV-2 spike protein in the human host

NATURE

Authors
Antoni G. Wrobel, Donald J. Benton, Chloë Roustan, Annabel Borg, Saira Hussain, Stephen R. Martin, Peter B. Rosenthal, John J. Skehel, Steven J. Gamblin

Abstract
Recently emerged variants of SARS-CoV-2 contain in their surface spike glycoproteins multiple substitutions associated with increased transmission and resistance to neutralising antibodies. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (Alpha) and B.1.351 (Beta) variants to better understand the evolution of the virus in humans. Spikes of both variants have the same mutation, N501Y, in the receptor-binding domains. This substitution confers tighter ACE2 binding, dependent on the common earlier substitution, D614G. Each variant spike has acquired other key changes in structure that likely impact virus pathogenesis. The spike from the Alpha variant is more stable against disruption upon binding ACE2 receptor than all other spikes studied. This feature is linked to the acquisition of a more basic substitution at the S1-S2 furin site (also observed for the variants of concern Delta, Kappa, and Omicron) which allows for near-complete cleavage. In the Beta variant spike, the presence of a new substitution, K417N (also observed in the Omicron variant), in combination with the D614G, stabilises a more open spike trimer, a conformation required for receptor binding. Our observations suggest ways these viruses have evolved to achieve greater transmissibility in humans.

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18/02/2022 Correspondence
Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Var...

Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants

THE LANCET

Authors
Shabir A Madhi, Chikwe Ihekweazu, Helen Rees, Andrew J Pollard

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18/02/2022 Correspondence
Decoupling of omicron variant infections and severe COVID-19

THE LANCET

Authors
Shabir A Madhi, Chikwe Ihekweazu, Helen Rees, Andrew J Pollard

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09/02/2022 Correspondence
Protection against the Omicron Variant from Previous SARS-CoV-2 Infect...

Protection against the Omicron Variant from Previous SARS-CoV-2 Infection

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
V.V.A.A.

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02/02/2022 PERSPECTIVE
Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron V...

Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Roby P. Bhattacharyya, William P. Hanage

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21/01/2022 Articles
Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicr...

Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron

NATURE

Authors
Huiping Shuai, Jasper Fuk-Woo Chan, Bingjie Hu, Yue Chai, Terrence Tsz-Tai Yuen, Feifei Yin, Xiner Huang, Chaemin Yoon, Jing-Chu Hu, Huan Liu, Jialu Shi, Yuanchen Liu, Tianrenzheng Zhu, Jinjin Zhang, Yuxin Hou, Yixin Wang, Lu Lu, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Melinda A. Brindley, Bao-Zhong Zhang, Jian-Dong Huang, Kelvin Kai-Wang To, Kwok-Yung Yuen, Hin Chu

Abstract
SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human population1. While recent reports reveal that the Omicron variant robustly escapes from vaccine and therapeutic neutralization antibodies2-10, the pathogenicity of the virus remains unknown. Here we show that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 cells. Further mechanistic investigations reveal that the Omicron variant is inefficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. Omicron replication is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is attenuated in virus replication and pathogenicity in mice in comparison with WT and previous variants.

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20/01/2022 Report
SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of ...

SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein–ACE2 complex

SCIENCE

Authors
Dhiraj Mannar, James W. Saville, Xing Zhu, Shanti S. Srivastava, Alison M. Berezuk, Katharine S. Tuttle, Ana Citlali Marquez, Inna Sekirov, Sriram Subramaniam

Abstract
The newly reported Omicron variant is poised to replace Delta as the most prevalent SARS-CoV-2 variant across the world. Cryo-EM structural analysis of the Omicron variant spike protein in complex with human ACE2 reveals new salt bridges and hydrogen bonds formed by mutated residues R493, S496 and R498 in the RBD with ACE2. These interactions appear to compensate for other Omicron mutations such as K417N known to reduce ACE2 binding affinity, resulting in similar biochemical ACE2 binding affinities for Delta and Omicron variants. Neutralization assays show that pseudoviruses displaying the Omicron spike protein exhibit increased antibody evasion. The increase in antibody evasion, together with retention of strong interactions at the ACE2 interface, thus represent important molecular features that likely contribute to the rapid spread of the Omicron variant.

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11/01/2022 Articles
Predicting the mutational drivers of future SARS-CoV-2 variants of con...

Predicting the mutational drivers of future SARS-CoV-2 variants of concern

SCIENCE

Authors
M. Cyrus Maher, Istvan Bartha, Steven Weaver, Julia di Iulio, Elena Ferri, Leah Soriaga, Florian A. Lempp, Brian L. Hie, Bryan Bryson, Bonnie Berger, David L. Robertson, Gyorgy Snell, Davide Corti, Herbert W. Virgin, Sergei L. Kosakovsky Pond, Amalio Telenti

Abstract
SARS-CoV-2 evolution threatens vaccine- and natural infection-derived immunity as well as the efficacy of therapeutic antibodies. To improve public health preparedness, we sought to predict which existing amino acid mutations in SARS-CoV-2 might contribute to future variants of concern. We tested the predictive value of features comprising epidemiology, evolution, immunology, and neural network-based protein sequence modeling, and identified primary biological drivers of SARS-CoV-2 intra-pandemic evolution. We found evidence that ACE2-mediated transmissibility and resistance to population-level host immunity has waxed and waned as a primary driver of SARS-CoV-2 evolution over time. We retroactively identified with high accuracy (area under the receiver operator characteristic curve, AUROC=0.92-0.97) mutations that will spread, at up to four months in advance, across different phases of the pandemic. The behavior of the model was consistent with a plausible causal structure wherein epidemiological covariates combine the effects of diverse and shifting drivers of viral fitness. We applied our model to forecast mutations that will spread in the future and characterize how these mutations affect the binding of therapeutic antibodies. These findings demonstrate that it is possible to forecast the driver mutations that could appear in emerging SARS-CoV-2 variants of concern. We validate this result against Omicron, showing elevated predictive scores for its component mutations prior to emergence, and rapid score increase across daily forecasts during emergence. This modeling approach may be applied to any rapidly evolving pathogens with sufficiently dense genomic surveillance data, such as influenza, and unknown future pandemic viruses.

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02/12/2021 Articles
Structural basis for continued antibody evasion by the SARS-CoV-2 rece...

Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain

SCIENCE

Authors
Katherine G. Nabel, Sarah A. Clark, Sundaresh Shankar, Junhua Pan, Lars E. Clark, Pan Yang, Adrian Coscia, Lindsay G. A. McKay, Haley H. Varnum, Vesna Brusic, Nicole V. Tolan, Guohai Zhou, Michaël Desjardins, Sarah E. Turbett, Sanjat Kanjilal, Amy C. Sherman, Anand Dighe, Regina C. LaRocque, Edward T. Ryan, Casey Tylek, Joel F. Cohen-Solal, Anhdao T. Darcy, Davide Tavella, Anca Clabbers, Yao Fan, Anthony Griffiths, Ivan R. Correia, Jane Seagal, Lindsey R. Baden, Richelle C. Charles, Jonathan Abraham

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29/11/2021 News
Covid-19: Omicron may be more transmissible than other variants and pa...

Covid-19: Omicron may be more transmissible than other variants and partly resistant to existing vaccines, scientists fear

THE BMJ

Authors
Ingrid Torjesen

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17/08/2021 New Result
Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 ...

Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant

BIORXIV

Authors
Jun Zhang, Tianshu Xiao, Yongfei Cai, Christy L. Lavine, Hanqin Peng, Haisun Zhu, Krishna Anand, Pei Tong, Avneesh Gautam, Megan L. Mayer, Richard M. Walsh Jr., Sophia Rits-Volloch, Duane R. Wesemann, Wei Yang, Michael S. Seaman, Jianming Lu, Bing Chen

Abstract
The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report here structure, function and antigenicity of its full-length spike (S) trimer in comparison with those of other variants, including Gamma, Kappa, and previously characterized Alpha and Beta. Delta S can fuse membranes more efficiently at low levels of cellular receptor ACE2 and its pseudotyped viruses infect target cells substantially faster than all other variants tested, possibly accounting for its heightened transmissibility. Mutations of each variant rearrange the antigenic surface of the N-terminal domain of the S protein in a unique way, but only cause local changes in the receptor-binding domain, consistent with greater resistance particular to neutralizing antibodies. These results advance our molecular understanding of distinct properties of these viruses and may guide intervention strategies.

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08/07/2021 PERSPECTIVE
After the pandemic: perspectives on the future trajectory of COVID-19

NATURE

Authors
Amalio Telenti, Ann Arvin, Lawrence Corey, Davide Corti, Michael S. Diamond, Adolfo García-Sastre, Robert F. Garry, Edward C. Holmes, Phil Pang, Herbert W. Virgin

Abstract
There is a realistic expectation that the global effort in vaccination will bring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic under control. Nonetheless, uncertainties remain about the type of long-term association the virus will establish with the human population, particularly whether the coronavirus disease 2019 (COVID-19) will become an endemic disease. Although the trajectory is difficult to predict, the conditions, concepts, and variables that influence this transition can be anticipated. Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fueled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection, and reentries from zoonotic reservoirs. Here, we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. There are key pieces of data that are urgently needed in order to make good decisions. We outline these and propose a way forward.

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07/07/2021 Articles
Genomic epidemiology of SARS‐CoV‐2 in the UAE reveals novel virus muta...

Genomic epidemiology of SARS‐CoV‐2 in the UAE reveals novel virus mutation, patterns of co‐infection and tissue specifc host immune response

NATURE

Authors
Rong Liu, Pei Wu, Pauline Ogrodzki, Sally Mahmoud, Ke Liang, Pengjuan Liu, Stephen S. Francis, Hanif Khalak, Denghui Liu, Junhua Li, Tao Ma, Fang Chen, Weibin Liu, Xinyu Huang, Wenjun He, Zhaorong Yuan, Nan Qiao, Xin Meng, Budoor Alqarni, Javier Quilez, Vinay Kusuma, Long Lin, Xin Jin, Chongguang Yang, Xavier Anton, Ashish Koshy, Huanming Yang, Xun Xu, Jian Wang, Peng Xiao, Nawal Al Kaabi, Mohammed Saifuddin Fasihuddin, Francis Amirtharaj Selvaraj, Stefan Weber, Farida Ismail Al Hosani, Siyang Liu, Walid Abbas Zaher

Abstract
To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world and that defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host–pathogen interaction investigation.

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04/06/2021 News
Covid-19: Delta variant is now UK’s most dominant strain and spreading...

Covid-19: Delta variant is now UK’s most dominant strain and spreading through schools

THE BMJ

Authors
Ingrid Torjesen

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30/05/2021 New Result
Human genome integration of SARS-CoV-2 contradicted by long-read seque...

Human genome integration of SARS-CoV-2 contradicted by long-read sequencing

BIORXIV

Authors
Nathan Smits, Jay Rasmussen, Gabriela O. Bodea, Alberto A. Amarilla, Patricia Gerdes, Francisco J. Sanchez-Luque, Prabha Ajjikuttira, Naphak Modhiran, Benjamin Liang, Jamila Faivre, Ira W. Deveson, Alexander A. Khromykh, Daniel Watterson, Adam D. Ewing, Geoffrey J. Faulkner

Abstract
A recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find any evidence of the virus existing as DNA. By examining ONT data from separate HEK293T cultivars, we resolved the complete sequences of 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events in vivo are highly unlikely to drive later oncogenesis or explain post-recovery detection of the virus.

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28/05/2021 New Result
The SARS-CoV-2 variants associated with infections in India, B.1.617, ...

The SARS-CoV-2 variants associated with infections in India, B.1.617, show enhanced spike cleavage by furin

BIORXIV

Authors
Thomas P. Peacock, Carol M. Sheppard, Jonathan C. Brown, Niluka Goonawardane, Jie Zhou, Max Whiteley, PHE Virology Consortium, Thushan I. de Silva, Wendy S. Barclay

Abstract
The spike (S) glycoprotein of the SARS-CoV-2 virus that emerged in 2019 contained a suboptimal furin cleavage site at the S1/S2 junction with the sequence 681PRRAR/S686. This cleavage site is required for efficient airway replication, transmission, and pathogenicity of the virus. The B.1.617 lineage has recently emerged in India, coinciding with substantial disease burden across the country. Early evidence suggests that B.1.617.2 (a sublineage of B.1.617) is more highly transmissible than contemporary lineages. B.1.617 and its sublineages contain a constellation of S mutations including the substitution P681R predicted to further optimise this furin cleavage site. We provide experimental evidence that virus of the B.1.617 lineage has enhanced S cleavage, that enhanced processing of an expressed B.1.617 S protein in cells is due to P681R, and that this mutation enables more efficient cleavage of a peptide mimetic of the B.1.617 S1/S2 cleavage site by recombinant furin. Together, these data demonstrate viruses in this emerging lineage have enhanced S cleavage by furin which we hypothesise could be enhancing transmissibility and pathogenicity.

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27/05/2021 New Result
Exploring the natural origins of SARS-CoV-2 in the light of recombinat...

Exploring the natural origins of SARS-CoV-2 in the light of recombination

BIORXIV

Authors
Spyros Lytras, Joseph Hughes, Darren Martin, Arné de Klerk, Rentia Lourens, Sergei L Kosakovsky Pond, Wei Xia, Xiaowei Jiang, David L Robertson

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27/05/2021 Correspondence
SARS-CoV-2 variants of concern are emerging in India

NATURE

Authors
Jasdeep Singh, Syed Asad Rahman, Nasreen Z. Ehtesham, Subhash Hira, Seyed E. Hasnain

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19/05/2021 Articles
Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE...

Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE-2 in humans and other species

CELL

Authors
Kefang Liu, Xiaoqian Pan, Linjie Li, Feng Yu, Anqi Zheng, Pei Du, Pengcheng Han, Yumin Meng, Yanfang Zhang, Lili Wu, Qian Chen, Chunli Song, Yunfei Jia, Sheng Niu, Dan Lu, Chengpeng Qiao, Zhihai Chen, Dongli Ma, Xiaopeng Ma, Shuguang Tan, Xin Zhao, Jianxun Qi, George F. Gao, Qihui Wang

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15/05/2021 New Result
Distinct mutations and lineages of SARS-CoV-2 virus in the early phase...

Distinct mutations and lineages of SARS-CoV-2 virus in the early phase of COVID-19 pandemic and subsequent global expansion

BIORXIV

Authors
Yan Chen, Shiyong Li, Wei Wu, Shuaipeng Geng, Mao Mao

Abstract
A novel coronavirus, SARS-CoV-2, has caused over 85 million cases and over 1.8 million deaths worldwide since it occurred twelve months ago in Wuhan, China. Here we conceptualized the time-series evolutionary and expansion dynamics of SARS-CoV-2 by taking a series of cross-sectional view of viral genomes from early outbreak in January in Wuhan to early phase of global ignition in early April, and finally to the subsequent global expansion by late December 2020. By scrutinizing cases from early outbreak, we found a viral genotype from the Seafood Market in Wuhan featured with two concurrent mutations has become the overwhelmingly dominant genotype (95.7%) of the pandemic. By analyzing 4,013 full-length SARS-CoV-2 genomes from different continents by early April, we were able to visualize the genomic diversity over a 14-week timespan since the outbreak in Wuhan. 2,954 unique nucleotide substitutions were identified with 31 of the 4,013 genomes remaining as ancestral type, and 952 (32.2%) mutations recurred in more than one genome. 11 major viral genotypes with unique geographic distributions were identified. As the pandemic has been unfolding for more than one year, we also used the same approach to analyze 261,323 full-length SARS-CoV-2 genomes from the world since the outbreak in Wuhan (i.e. including all the available viral genomes in the GISAID database as of 25 December 2020) in order to recapitulate our findings in a real-time fashion and to present a full catalogue of SARS-CoV-2 mutations. We demonstrated the viral genotypic dynamics from different geographic locations over one-year timespan reveal transmission routes and indicate subsequent expansion. This study, to our knowledge, is heretofore the largest and most comprehensive genomic study of SARS-CoV-2. It indicates the viral genotypes can be utilized as molecular barcodes in combination with epidemiologic data to monitor the spreading routes of the pandemic and evaluate the effectiveness of control measures. Moreover, the dynamics of viral mutational spectrum in the study may help the early identification of new strains in patients to reduce further spread of infection, and guide the development of molecular diagnosis and vaccines against COVID-19, and last but not the least help assess their accuracy and efficacy.

Evidence before this study As the COVID-19 pandemic continues, in order to mitigate the risk of further regional expansions as well as to estimate the effectiveness of control measures in various regions, viral genomic studies on its origins, transmission routes and expansion models have begun to surge. Several studies on the genomics of SARS-CoV-2 virus have offered clues of the origins, and transmission path of the disease. However, due to lack of early samples, a limited number of SARS-CoV-2 genomes, and/or focusing on specific geographic locations, we still lack a complete global view of the expansion of COVID-19 in the context of the viral mutational spectrum.

Added value of this study In this study we provide a global view of the mutation dynamic and transmission routes of SARS-CoV-2 with a foothold on the early phase of the pandemic. This is also the largest and the most comprehensive SARS-CoV-2019 viral genome study and molecular epidemiology study that provides an unprecedented time window to study mutations and evolution of SARS-CoV-2. The unique molecular barcodes defined by Strain of Origin (SOO) algorithm can be utilized to prospectively monitor the spreading trajectory and reveal the expansion of the ongoing pandemic. Our full catalogue of SARS-CoV-2 mutations can also guide the development and help assess the accuracy of molecular diagnosis and the efficacy of the vaccines against COVID-19.

Implications of all the available evidence The results that we presented here serve as a proof of concept to demonstrate the utility of large-scale viral genome sequencing during a novel pathogen outbreak. Ramping up sampling in a real-time manner may generate high-resolution maps of who-infected-whom transmission at community level and reveal the subsequent expansion patterns which are especially crucial for the most severely stricken countries and regions to promptly develop tailored mitigation plans.

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13/05/2021 Editorial
Effectiveness of England’s initial vaccine roll out

THE BMJ

Authors
Andreas Martin Lisewski

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10/05/2021 Articles
A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal s...

A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality

MEDRXIV

Authors
Pierre Fillatre, Marie-José Dufour, Sylvie Behillil, Remi Vatan, Pascale Reusse, Alice Gabellec, Nicolas Velmans, Catherine Montagne, Sophie Geffroy, Edith Droumaguet, Véronique Merour, Vincent Enouf, Rodolphe Buzele, Marion Valence, Elena Guillotel, Bertrand Gagniere, Artem Baidaluk, Anna Zhukova, Mathieu Tourdjman, Vincent Thibault, Claire Grolhier, Charlotte Pronier, Xavier Lescure, Etienne Simon-Loriere, Dominique Costagliola, Sylvie Van Der Werf, Pierre Tattevin, Nicolas Massart

ABSTRACT
Background In early January 2021, an outbreak of nosocomial cases of COVID-19 emerged in Western France, with RT-PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS-CoV-2 lineage: B.1.616. In March, WHO classified this variant as ‘under investigation’ (VUI). We analyzed the characteristics and outcomes of COVID-19 cases related to this new variant.

Methods Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled patients with at least one of the following: i) positive SARS-CoV-2 RT-PCR on a respiratory sample; ii) seroconversion with anti-SARS-CoV-2 IgG/IgM; iii) suggestive symptoms and typical features of COVID-19 on chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown.

Findings From January 1st to March 24th, 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n=34), VOC (n=32), and unknown (n=48). B.1.616-related cases were older than VOC-related cases (81 years [73-88], vs 73 years [67-82], P<0.05) and their first RT-PCR tests were less often positive (5/34, 15% vs 31/32, 97%, P<0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.2 [1.3– 13.5], P=0.018), and increased lethality (logrank test P=0.01): 28-day mortality 15/34 (44%) with B.1.616, vs. 5/32 (16%) for VOC, P=0.036.

Interpretation We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, poorly detected by RT-PCR on nasopharyngeal samples, with high lethality.

Evidence before this study Among the numerous SARS-CoV-2 variants described worldwide, only 3 are currently classified as Variant of Concern (VOC) by the WHO, since they are associated with either an increased risk in transmissibility, severity, or significant reduction in neutralization by antibodies: B.1.1.7, B.1.351 and P.1 (Pango lineage nomenclature). With the ongoing circulation of SARS-CoV-2 in many places worldwide, the emergence of new variants may reduce the efficacy of vaccines and jeopardize our prospects to control the pandemic. In early January 2021, an outbreak of cases highly suggestive of COVID-19 despite negative RT-PCR tests on repeated nasopharyngeal (NP) samples was reported in Western France, leading to several nosocomial clusters. Whole-genome sequencing (WGS) from lower respiratory tract samples identified a new lineage of SARS-CoV-2 virus, classified as B1.616. Consequently, the French public health agency (Santé publique France) and the WHO classified B.1.616 as ‘variant under investigation’ (VUI).

Added value of this study Our observational study, conducted from January 1st to March 24th 2021 in the B.1.616 identified area, provides the first clinical and virological description of B.1.616-associated COVID-19. The 34 cases had clinical, biological and radiological findings in line with classical features of COVID-19, while RT-PCR tests on nasopharyngeal (NP) samples failed to detect SARS-CoV-2 in most patients. Indeed, this gold-standard test was positive in only 15% of the first tests in B.1.616-related COVID-19 patients. Of note, the diagnostic performance of RT-PCR tests was satisfactory on lower respiratory tract samples, suggesting that failure to detect B.1.616 on NP samples would be due to a viral load below the limit of detection in the upper respiratory tract, rather than to genomic mismatches between routine RT-PCR targets and this variant. In our cohort, B.1.616 was independently associated with worse clinical outcome, with high 28-day mortality (44%).

Implications of all the available evidence Diagnosis of B.1.616-related COVID-19 cases should not rely on RT-PCR tests on NP samples. In the epidemic area, strict infection control measures must be maintained as long as COVID-19 diagnosis is not ruled out, in order to limit nosocomial clusters and case fatality. Further studies are needed to confirm and investigate the association between genomic characteristics of B.1.616, and i) poor detection by RT-PCR tests on NP samples; ii) prognosis.

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30/04/2021 Articles
COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in ...

COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program - Kentucky, March 2021

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Alyson M Cavanaugh, Sarah Fortier, Patricia Lewis, Vaneet Arora, Matt Johnson, Karim George, Joshua Tobias, Stephanie Lunn, Taylor Miller, Douglas Thoroughman, Kevin B Spicer

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27/04/2021 New Result
The SARS-CoV-2 RNA interactome

ELSEVIER

Authors
Sungyul Lee, Young-suk Lee, Yeon Choi, Ahyeon Son, Youngran Park, Kyung-Min Lee, Jeesoo Kim, Jong-Seo Kim, V. Narry Kim

Abstract
SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs including ZC3HAV1, TRIM25, PARP12, and SHFL and 8 proviral RBPs such as EIF3D and CSDE1 which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.

24/04/2021 New Result
Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P...

Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India

BIORXIV

Authors
Sarah Cherian, Varsha Potdar, Santosh Jadhav, Pragya Yadav, Nivedita Gupta, Mousmi Das, Soumitra Das, View ORCID ProfileAnurag Agarwal, Sujeet Singh, Priya Abraham, Samiran Panda, Shekhar Mande, Renu Swarup, Balram Bhargava, Rajesh Bhushan, INSACOG Consortium

Abstract
As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains.

Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to selected monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation is warranted for accessing both ACE2 binding and the effectiveness of commonly elicited neutralizing mAbs for the strains of lineage B.1.617.

The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

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23/04/2021 Articles
Isolation of SARS-CoV-2 from the air in a car driven by a COVID patien...

Isolation of SARS-CoV-2 from the air in a car driven by a COVID patient with mild illness

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Authors
John A. Lednicky, Michael Lauzardo, Md. M. Alam, Maha A. Elbadry, Caroline J. Stephenson, Julia C. Gibson, J. Glenn Morris Jr.

Abstract
Objective
To determine if viable virus could be isolated from the air within a car driven by a patient infected with SARS-CoV-2, and to assess the size range of the infectious particles.
Methods
We used a Sioutas personal cascade impactor sampler (PCIS) to screen for SARS-CoV-2 in a car driven by a COVID-19 patient. The patient, who had only mild illness without fever or cough and was not wearing a mask, drove the car for 15 minutes with the air conditioning turned on and windows closed. The PCIS was clipped to the sun-visor above the front passenger seat and was retrieved from the car two hours after completion of the drive.
Results
SARS-CoV-2 was detectable at all PCIS stages by PCR and was cultured from the section of the sampler collecting particles in the 0.25 to 0.50 μm size range.
Conclusions
Our data highlight the potential risk of SARS-CoV-2 transmission by minimally symptomatic persons in the closed space inside of a car and suggest that a substantial component of that risk is via aerosolized virus.

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15/04/2021 Comment
Ten scientific reasons in support of airborne transmission of SARS-CoV...

Ten scientific reasons in support of airborne transmission of SARS-CoV-2

THE LANCET

Authors
Trisha Greenhalgh, Jose L Jimenez, Kimberly A Prather, Zeynep Tufekci, David Fisman, Robert Schooley

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15/04/2021 Articles
Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent a...

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

CELL PRESS

Authors
Piyada Supasa, Daming Zhou, Wanwisa Dejnirattisai, ..., Jingshan Ren, David I. Stuart, Gavin R. Screaton

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12/04/2021 Articles
Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SAR...

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

NATURE

Authors
Alexey Stukalov, Virginie Girault, Vincent Grass, Ozge Karayel, Valter Bergant, Christian Urban, Darya A. Haas, Yiqi Huang, Lila Oubraham, Anqi Wang, M. Sabri Hamad, Antonio Piras, Fynn M. Hansen, Maria C. Tanzer, Igor Paron, Luca Zinzula, Thomas Enghleitner, Maria Reinecke, Teresa M. Lavacca, Rosina Ehmann, Roman Wölfel, Jörg Jores, Bernhard Kuster, Ulrike Protzer, Roland Rad, John Ziebuhr, Volker Thiel, Pietro Scaturro, Matthias Mann, Andreas Pichlmair

Abstract
The global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19 pathophysiology1–10. Integration of such datasets to obtain a holistic view of virus-host interactions and to define the pathogenic properties of SARS-CoV-2 is limited by the heterogeneity of the experimental systems. We therefore conducted a concurrent multi-omics study of SARS-CoV-2 and SARS-CoV. Using state-of-the-art proteomics, we profiled the interactome of both viruses, as well as their influence on transcriptome, proteome, ubiquitinome and phosphoproteome in a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed crosstalk between the perturbations taking place upon SARS-CoV-2 and SARS-CoV infections at different layers and identified unique and common molecular mechanisms of these closely related coronaviruses. The TGF-β pathway, known for its involvement in tissue fibrosis, was specifically dysregulated by SARS-CoV-2 ORF8 and autophagy by SARS-CoV-2 ORF3. The extensive dataset (available at https://covinet.innatelab.org) highlights many hotspots that can be targeted by existing drugs and it can guide rational design of virus- and host-directed therapies, which we exemplify by identifying kinase and MMPs inhibitors with potent antiviral effects against SARS-CoV-2.

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09/04/2021 Articles
Rise of Variants in Europe Shows How Dangerous the Virus Can Be

THE NEW YORK TIMES

Authors
Josh Holder, Allison McCann, Benjamin Mueller

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06/04/2021 New Result
Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses

BIORXIV

Authors
Matthew Cotten, David L. Robertson, V.T. Phan

Abstract
Defining the unique protein features of SARS-CoV-2, the viral agent causing Coronavirus Disease 2019, may guide efforts to control this pathogen. We examined proteins encoded by the Sarbecoviruses closest to SARS-CoV-2 using profile Hidden Markov Model similarities to identify features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2. The analysis provided a measure of total proteome similarity and showed that a small subset of bat Sarbecoviruses are closely related but unlikely to be the direct source of SARS-CoV-2. Spike analysis reveals that the current SARS-CoV-2 variants of concern have sampled only 36% of the possible spikes changes which have occurred historically in Sarbecovirus evolution. It is likely that new SARS-CoV-2 variants with changes in these regions are compatible with virus replication and are to be expected in the coming months, unless global viral replication is severely reduced.

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05/04/2021 Articles
Community Transmission of SARS-CoV-2 Associated with a Local Bar Openi...

Community Transmission of SARS-CoV-2 Associated with a Local Bar Opening Event — Illinois, February 2021

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Samira Sami, Caitlin R. Turbyfill, Shelby Daniel-Wayman, Stacy Shonkwiler, Kiva A. Fisher; Macey Kuhring; Aaron M. Patrick; Stephanie Hinton, Amanda S. Minor, Jessica N. Ricaldi, Ngozi Ezike, Judy Kauerauf, Wayne A. Duffus

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05/04/2021 Brief Report
Analyzing the vast coronavirus literature with CoronaCentral

PNAS

Authors
Jake Lever, Russ B. Altman

Abstract
The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as “long COVID” and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.

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04/04/2021 Articles
Troubling "Eek" variant found in most Tokyo hospital COVID cases - NHK

REUTERS

Authors
Reuters Staff

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04/04/2021 Articles
A novel variant of interest of SARS-CoV-2 with multiple spike mutation...

A novel variant of interest of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa

MEDRXIV

Authors
Tulio de Oliveira, Silvia Lutucuta, John Nkengasong, Joana Morais, Joana Paula Paixão, Zoraima Neto, Pedro Afonso, Julio Miranda, Kumbelembe David, Luzia Inglês, Amilton Pereira Agostinho Paulo Raisa Rivas Carralero, Helga Reis Freitas, Franco Mufinda, Sofonias Kifle Tessema, Houriiyah Tegally, Emmanuel James San, Eduan Wilkinson, Jennifer Giandhari, Sureshnee Pillay, Marta Giovanetti, Yeshnee Naidoo, Aris Katzourakis, Mahan Ghafari, Lavanya Singh, Derek Tshiabuila, Darren Martin, Richard J Lessells

Abstract
At the end of 2020, the Network for Genomic Surveillance in South Africa (NGS-SA) detected a SARS-CoV-2 variant of concern (VOC) in South Africa (501Y.V2 or PANGO lineage B.1.351)1. 501Y.V2 is associated with increased transmissibility and resistance to neutralizing antibodies elicited by natural infection and vaccination2,3. 501Y.V2 has since spread to over 50 countries around the world and has contributed to a significant resurgence of the epidemic in southern Africa. In order to rapidly characterize the spread of this and other emerging VOCs and variants of interest (VOIs), NGS-SA partnered with the Africa Centres for Disease Control and Prevention and the African Society of Laboratory Medicine through the Africa Pathogen Genomics Initiative to strengthen SARS-CoV-2 genomic surveillance across the region.

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01/04/2021 Articles
Computational epitope map of SARS-CoV-2 spike protein

PLOS

Authors
Mateusz SikoraI, So ̈ren von Bu ̈lowI, Florian E. C. BlancI, Michael GechtI, Roberto CovinoI, Gerhard HummerI

Abstract
The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.

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30/03/2021 Comment
Pandemic moves and countermoves: vaccines and viral variants

THE LANCET

Authors
Rogier W Sanders, Menno D de Jong

Read More »

29/03/2021 Case Report
Risk of SARS-CoV-2 transmission from ne...nted previous infection or v...

Risk of SARS-CoV-2 transmission from ne...nted previous infection or vaccination

ECDC

Authors
ECDC (European Centre for Disease Prevention and Control)

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26/03/2021 Viewpoint
The emerging plasticity of SARS-CoV-2

SCIENCE

Authors
Kevin D. McCormick, Jana L. Jacobs, John W. Mellors

Read More »

22/03/2021 Articles
Transmissibility and transmission of respiratory viruses

NATURE

Authors
Nancy H. L. Leung

Abstract
Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R0) or secondary attack rate is heterogeneous for the same virus. Respiratory viruses can be transmitted via four major modes of transmission: direct (physical) contact, indirect contact (fomite), (large) droplets and (fine) aerosols. We know little about the relative contribution of each mode to the transmission of a particular virus in different settings, and how its variation affects transmissibility and transmission dynamics. Discussion on the particle size threshold between droplets and aerosols and the importance of aerosol transmission for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is ongoing. Mechanistic evidence supports the efficacies of non-pharmaceutical interventions with regard to virus reduction; however, more data are needed on their effectiveness in reducing transmission. Understanding the relative contribution of different modes to transmission is crucial to inform the effectiveness of non-pharmaceutical interventions in the population. Intervening against multiple modes of transmission should be more effective than acting on a single mode.

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18/03/2021 New Result
12 Months of COVID-19 Eliminated 12 Years of Progress in the Global Fi...

12 Months of COVID-19 Eliminated 12 Years of Progress in the Global Fight Against Tuberculosis\

STOP TB PARTNERSHIP

Authors
Stop TB PARTNERSHIP

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12/03/2021 Articles
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced ...

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

CELL

Authors
Wilfredo F. Garcia-Beltran, Evan C. Lam, Kerri St. Denis, Adam D. Nitido, Zeidy H. Garcia, Blake M. Hauser, Jared Feldman, Maia N. Pavlovic, David J. Gregory, Mark C. Poznansky, Alex Sigal, Aaron G. Schmidt, A. John Iafrate, Vivek Naranbhai, Alejandro B. Balazs

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08/03/2021 Articles
Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

NATURE

Authors
Pengfei Wang, Manoj S. Nair, Lihong Liu, Sho Iketani, Yang Luo, Yicheng Guo, Maple Wang, Jian Yu, Baoshan Zhang, Peter D. Kwong, Barney S. Graham, John R. Mascola, Jennifer Y. Chang, Michael T. Yin, Magdalena Sobieszczyk, Christos A. Kyratsous, Lawrence Shapiro, Zizhang Sheng, Yaoxing Huang, David D. Ho

Abstract
The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. The prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization1–3, with more in the pipeline4–7. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-199,10. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of the spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

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04/03/2021 Articles
Resistance of SARS-CoV-2 variants to neutralization by monoclonal and ...

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

NATURE

Authors
Rita E. Chen, Xianwen Zhang, James Brett Case, Emma S. Winkler, Yang Liu, Laura A. VanBlargan, Jianying Liu, John M. Errico, Xuping Xie, Naveenchandra Suryadevara, Pavlo Gilchuk, Seth J. Zost, Stephen Tahan, Lindsay Droit, Jackson S. Turner, Wooseob Kim, Aaron J. Schmitz, Mahima Thapa, David Wang, Adrianus C. M. Boon, Rachel M. Presti, Jane A. O’Halloran, Alfred H. J. Kim, Parakkal Deepak, Dora Pinto, Daved H. Fremont, James E. Crowe Jr, Davide Corti, Herbert W. Virgin, Ali H. Ellebedy, Pei-Yong Shi, Michael S. Diamond

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.

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04/03/2021 Original Investigation
SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 Fr...

SARS-CoV-2 on Ocular Surfaces in a Cohort of Patients With COVID-19 From the Lombardy Region, Italy

JAMA

Authors
Claudio Azzolini, Simone Donati, Elias Premi, Andreina Baj, Claudia Siracusa, Angelo Genoni, Paolo A. Grossi, Lorenzo Azzi, Fausto Sessa, Francesco Dentali, Paolo Severgnini, Giulio Minoja, Luca Cabrini, Maurizio Chiaravalli, Giovanni Veronesi, Giulio Carcano, Lorenzo S. Maffioli, Angelo Tagliabue

Abstract
Importance Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears.

Objectives To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions.

Design, Setting, and Participants Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test.

Exposure SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs.

Main Outcomes and Measures Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data.

Results A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus.

Conclusions and Relevance In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.

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03/03/2021 Viewpoint
The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a...

The Potential Future of the COVID-19 Pandemic Will SARS-CoV-2 Become a Recurrent Seasonal Infection?

JAMA

Authors
Christopher J. L. Murray, Peter Piot

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26/02/2021 Articles
SARS-CoV-2 spike D614G change enhances replication and transmission

NATURE

Authors
Bin Zhou, Tran Thi Nhu Thao, Donata Hoffmann, Adriano Taddeo, Nadine Ebert, Fabien Labroussaa, Anne Pohlmann, Jacqueline King, Silvio Steiner, Jenna N. Kelly, Jasmine Portmann, Nico Joel Halwe, Lorenz Ulrich, Bettina Salome Trüeb, Xiaoyu Fan, Bernd Hoffmann, Li Wang, Lisa Thomann, Xudong Lin, Hanspeter Stalder, Berta Pozzi, Simone de Brot, Nannan Jiang, Dan Cui, Jaber Hossain, Malania Wilson, Matthew Keller, Thomas J. Stark, John R. Barnes, Ronald Dijkman, Joerg Jores, Charaf Benarafa, David E. Wentworth, Volker Thiel, Martin Beer

Abstract
During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic1. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human host cell surface receptor angiotensin-converting enzyme 2 (ACE2), (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

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26/02/2021 PERSPECTIVE
SARS-CoV-2 dependence on host pathways

SCIENCE

Authors
Jason P. Wong, Blossom Damania

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23/02/2021 Articles
One Year of SARS-CoV-2 Evolution

ONE YEAR OF SARS-COV-2 EVOLUTION

Authors
Aiping Wu, Lulan Wang, Hang-Yu Zhou, Cheng-Yang Ji, Shang Zhou Xia, Yang Cao, Jing Meng, Xiao Ding, Sarah Gold, Taijiao Jiang, Genhong Cheng

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23/02/2021 Original Investigation
Densely sampled viral trajectories suggest longer duration of acute in...

Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2

HARVARD LIBRARY

Authors
Stephen M. Kissler, Joseph R. Fauver, Christina Mack, Caroline G. Tai, Mallery I. Breban, Anne E. Watkins, Radhika M. Samant, Deverick J. Anderson, David D. Ho, Nathan D. Grubaugh, Yonatan H. Grad

Abstract
To test whether acute infection with B.1.1.7 is associated with higher or more sustained nasopharyngeal viral concentrations, we assessed longitudinal PCR tests performed in a cohort of 65 individuals infected with SARS-CoV-2 undergoing daily surveillance testing, including seven in fected with B.1.1.7. For individuals infected with B.1.1.7, the mean duration of the proliferation phase was 5.3 days (90% credible interval [2.7, 7.8]), the mean duration of the clearance phase was 8.0 days [6.1, 9.9], and the mean overall duration of infection (proliferation plus clearance) was 13.3 days [10.1, 16.5]. These compare to a mean proliferation phase of 2.0 days [0.7, 3.3], a mean clearance phase of 6.2 days [5.1, 7.1], and a mean duration of infection of 8.2 days [6.5, 9.7] for non-B.1.1.7 virus. The peak viral concentration for B.1.1.7 was 19.0 Ct [15.8, 22.0] compared to 20.2 Ct [19.0, 21.4] for non-B.1.1.7. This converts to 8.5 log10 RNA copies/ml [7.6, 9.4] for B.1.1.7 and 8.2 log10 RNA copies/ml [7.8, 8.5] for non-B.1.1.7. These data offer evidence that SARS-CoV-2 variant B.1.1.7 may cause longer infections with similar peak viral concentration compared to non-B.1.1.7 SARS-CoV-2. This extended duration may contribute to B.1.1.7 SARS CoV-2’s increased transmissibility.

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13/02/2021 Articles
The antigenic anatomy of SARS-CoV-2 receptor binding domain

CELL

Authors
Wanwisa Dejnirattisai, Daming Zhou, Helen M. Ginn, Helen M.E. Duyvesteyn, Piyada Supasa, James Brett Case, Yuguang Zhao, Thomas S. Walter, Alexander J. Mentzer, Chang Liu, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Natasha M. Kafai, Adam L. Bailey, Rita E. Chen, Baoling Ying, Craig Thompson, Jai Bolton, Alex Fyfe, Sunetra Gupta, Tiong Kit Tan, Javier Gilbert- Jaramillo, William James, Michael Knight, Miles W. Carroll, Donal Skelly, Christina Dold, Yanchun Peng, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Nigel Temperton, David R. Hall, Mark A. Williams, Neil G. Paterson, Felicity K.R. Bertram, C. Alistair Seibert, Daniel K. Clare, Andrew Howe, Julika Raedecke, Yun Song, Alain R. Townsend, Kuan-Ying A. Huang, Elizabeth E. Fry, Juthathip Mongkolsapaya, Michael S. Diamond, Jingshan Ren, David I. Stuart, Gavin R. Screaton

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11/02/2021 Letter
Emergence of a Novel SARS-CoV-2 Variant in Southern California

JAMA

Authors
Wenjuan Zhang, Brian D. Davis, Stephanie S. Chen, Jorge M. Sincuir Martinez, Jasmine T. Plummer, Eric Vail

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11/02/2021 Comment
SARS-CoV-2 variants and ending the COVID-19 pandemic

THE LANCET

Authors
Arnaud Fontanet, Brigitte Autran, Bruno Lina, Marie Paule Kieny, Salim S Abdool Karim, Devi Sridhar

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11/02/2021 Editorial
SARS-CoV-2 Viral Variants—Tackling a Moving Target

JAMA

Authors
John R. Mascola, Barney S. Graham, Anthony S. Fauci

Read More »

11/02/2021 Articles
Saliva is a reliable and accessible source for the detection of SARS-C...

Saliva is a reliable and accessible source for the detection of SARS-CoV-2

ELSEVIER

Authors
AA.VV.

Abstract
Objectives
The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated.

Methods
A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components.

Results
The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C.

Conclusions
The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.

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11/02/2021 Articles
COVID-19 re-infection: Diagnostic challenges and proposed diagnostic c...

COVID-19 re-infection: Diagnostic challenges and proposed diagnostic criteria

ELSEVIER

Authors
A.V.Raveendran

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10/02/2021 PERSPECTIVE
Experts Discuss COVID-19—Vaccine Questions, School Openings, and More

JAMA

Authors
Rochelle P. Walensky, Paul A. Offit, Christopher W. Seymour, Arnold S. Monto, Nicholas Christakis

Read More »

10/02/2021 Letter
Imported SARS-COV-2 Variant P.1 Detected in Traveler Returning from Br...

Imported SARS-COV-2 Variant P.1 Detected in Traveler Returning from Brazil to Italy

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Fabrizio Maggi, Federica Novazzi, Angelo Genoni, Andreina Baj, Pietro Giorgio Spezia, Daniele Focosi, Cristian Zago, Alberto Colombo, Gianluca Cassani, Renee Pasciuta, Antonio Tamborini, Agostino Rossi, Martina Prestia, Riccardo Capuano, Lorenzo Azzi, Annalisa Donadini, Giuseppe Catanoso, Paolo Antonio Grossi, Lorenzo Maffioli, Gianni Bonelli

Abstract
We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.

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09/02/2021 Articles
Evidence for SARS-CoV-2 related coronaviruses circulating in bats and ...

Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia

NATURE

Authors
Supaporn Wacharapluesadee, Chee Wah Tan, Patarapol Maneeorn, Prateep Duengkae, Feng Zhu, Yutthana Joyjinda, Thongchai Kaewpom, Wan Ni Chia, Weenassarin Ampoot, Beng Lee Lim, Kanthita Worachotsueptrakun, Vivian Chih-Wei Chen, Nutthinee Sirichan, Chanida Ruchisrisarod, Apaporn Rodpan, Kirana Noradechanon, Thanawadee Phaichana, Niran Jantarat, Boonchu Thongnumchaima, Changchun Tu, Gary Crameri, Martha M. Stokes, Thiravat Hemachudha, Lin-Fa Wang

Abstract
Among the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.

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08/02/2021 Correspondence
CovMT: an interactive SARS-CoV-2 mutation tracker, with a focus on cri...

CovMT: an interactive SARS-CoV-2 mutation tracker, with a focus on critical variants

THE LANCET

Authors
*Intikhab Alam, Aleksandar Radovanovic, Roberto Incitti, Allan A Kamau, Mohammed Alarawi, Esam I Azhar, Takashi Gojobori

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08/02/2021 Articles
Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 ...

Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 Protein-Protein Interaction

BIOPHYSICAL JOURNAL

Authors
Wenpeng Cao, Chuqiao Dong, Seonghan Kim, Decheng Hou, Wanbo Tai, Lanying Du, Wonpil Im, X. Frank Zhang

ABSTRACT
The current COVID-19 pandemic has led to a devastating impact across the world.
SARS-CoV-2 (the virus causing COVID-19) is known to use the receptor-binding domain
(RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2
(ACE2) receptor expressed on many human cell types. The RBD−ACE2 interaction is a crucial
step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2
interaction with the SARS-CoV-2 S protein has a higher affinity than its binding with the
structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS
outbreak. However, the biophysical mechanism behind such binding affinity difference is
unclear. This study utilizes combined single-molecule force spectroscopy and steered molecular
dynamics (SMD) simulation approaches to quantify the specific interactions between CoV-2 or
CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between CoV-2
RBD and ACE2 range from 70 to 105 pN and are 30-40% higher than those of CoV-1 RBD and
ACE2 under similar loading rates. SMD results indicate that CoV-2 RBD interacts with the Nlinked glycan on Asn90 of ACE2. This interaction is mostly absent in the CoV-1 RBD−ACE2
complex. During the SMD simulations, the extra RBD-N-glycan interaction contributes to a
greater force and prolonged interaction lifetime. The observation is confirmed by our
experimental force spectroscopy study. After removing N-linked glycans on ACE2, its
mechanical binding strength with CoV-2 RBD decreases to a similar level of the CoV-1
RBD−ACE2 interaction. Together, the study uncovers the mechanism behind the difference in
ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies
to block SARS-CoV-2 entry

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05/02/2021 Articles
SARS-CoV-2 evolution during treatment of chronic infection

NATURE

Authors
Steven A. Kemp, Dami A. Collier, Rawlings P. Datir, Isabella A. T. M. Ferreira, Salma Gayed, Aminu Jahun, Myra Hosmillo, Chloe Rees-Spear, Petra Mlcochova, Ines Ushiro Lumb, David J. Roberts, Anita Chandra, Nigel Temperton, The CITIID-NIHR BioResource COVID-19 Collaboration, The COVID-19 Genomics UK (COG-UK) Consortium, Katherine Sharrocks, Elizabeth Blane, Yorgo Modis, Kendra Leigh, John Briggs, Marit van Gils, Kenneth G. C. Smith, John R. Bradley, Chris Smith, Rainer Doffinger, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, David D. Pollock, Richard A. Goldstein, Anna Smielewska, Jordan P. Skittrall, Theodore Gouliouris, Ian G. Goodfellow, Effrossyni Gkrania-Klotsas, Christopher J. R. Illingworth, Laura E. McCoy, Ravindra K. Gupta

Abstract
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE21, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.

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04/02/2021 Articles
CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neu...

CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks

BIORXIV

Authors
Ellen D. Zhong, Tristan Bepler, Bonnie Berger, Joseph H. Davis

Abstract
Cryo-electron microscopy (cryo-EM) single-particle analysis has proven powerful in determining the structures of rigid macromolecules. However, many imaged protein complexes exhibit conformational and compositional heterogeneity that poses a major challenge to existing three-dimensional reconstruction methods. Here, we present cryoDRGN, an algorithm that leverages the representation power of deep neural networks to directly reconstruct continuous distributions of 3D density maps and map per-particle heterogeneity of single-particle cryo-EM datasets. Using cryoDRGN, we uncovered residual heterogeneity in high-resolution datasets of the 80S ribosome and the RAG complex, revealed a new structural state of the assembling 50S ribosome, and visualized large-scale continuous motions of a spliceosome complex. CryoDRGN contains interactive tools to visualize a dataset’s distribution of per-particle variability, generate density maps for exploratory analysis, extract particle subsets for use with other tools and generate trajectories to visualize molecular motions. CryoDRGN is open-source software freely available at http://cryodrgn.csail.mit.edu.

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03/02/2021 News
Scientists call for fully open sharing of coronavirus genome data

NATURE

Authors
Richard Van Noorden

Read More »

02/02/2021 Articles
What's Going On With All These Coronavirus Variants? An Illustrated Gu...

What's Going On With All These Coronavirus Variants? An Illustrated Guide

NPR

Authors
MICHAELEEN DOUCLEFF, MEREDITH RIZZO

Read More »

02/02/2021 Articles
The effect of the D614G substitution on the structure of the spike gly...

The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2

PNAS

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

Abstract
The majority of currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses have mutant spike glycoproteins that contain the D614G substitution. Several studies have suggested that spikes with this substitution are associated with higher virus infectivity. We use cryo-electron microscopy to compare G614 and D614 spikes and show that the G614 mutant spike adopts a range of more open conformations that may facilitate binding to the SARS-CoV-2 receptor, ACE2, and the subsequent structural rearrangements required for viral membrane fusion.

Read More »

29/01/2021 PERSPECTIVE
Insights from SARS-CoV-2 sequences

SCIENCE

Authors
Michael A. Martin, David VanInsberghe, Katia Koelle

Read More »

29/01/2021 Articles
Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant tha...

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

CELL

Authors
Jing-wen Lin, Chao Tang, Han-cheng Wei, Baowen Du, Chuan Chen, Minjin Wang, Yongzhao Zhou, Ming-xia Yu, Lu Cheng, Suvi Kuivanen, Natacha S. Ogando, Lev Levanov, Yuancun Zhao, Chang-ling Li, Ran Zhou, Zhidan Li, Yiming Zhang, Ke Sun, Chengdi Wang, Li Chen, Xia Xiao, Xiuran Zheng, Sha-sha Chen, Zhen Zhou, Ruirui Yang, Dan Zhang, Mengying Xu, Junwei Song, Danrui Wang, Yupeng Li, ShiKun Lei, Wanqin Zeng, Qingxin Yang, Ping He, Yaoyao Zhang, Lifang Zhou, Ling Cao, Feng Luo, Huayi Liu, Liping Wang, Fei Ye, Ming Zhang, Mengjiao Li, Wei Fan, Xinqiong Li, Kaiju Li, Bowen Ke, Jiannan Xu, Huiping Yang, Shusen He, Ming Pan, Yichen Yan, Yi Zha, Lingyu Jiang, Changxiu Yu, Yingfen Liu, Zhiyong Xu, Qingfeng Li, Yongmei Jiang, Jiufeng Sun, Wei Hong, Hongping Wei, Guangwen Lu, Olli Vapalahti, Yunzi Luo, Yuquan Wei, Thomas Connor, Wenjie Tan, Eric J. Snijder, Teemu Smura, Weimin Li, Jia Geng, Binwu Ying, Lu Chen

Read More »

29/01/2021 News
Nota técnica aborda Sars-CoV-2 e nova variante no AM

FIOCRUZ (FUNDACAO OSVALDO CRUZ)

Authors
Fiocruz Amazônia

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29/01/2021 News
Covid-19: Sore throat, fatigue, and myalgia are more common with new U...

Covid-19: Sore throat, fatigue, and myalgia are more common with new UK variant

THE BMJ

Authors
Elisabeth Mahase

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28/01/2021 Articles
Circulating SARS-CoV-2 spike N439K variants maintain fitness while eva...

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

CELL

Authors
Emma C. Thomson, Laura E. Rosen, James G. Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A. Wojcechowskyj, Chris Davis, Luca Piccoli, David J. Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O’Toole, Dora Pinto, Rachel M. Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B. Sreenu, Jay Nix, Ivy Zhang, Ruth F. Jarrett, William G. Glass, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Tristan I. Croll, Natasha Johnson, Julia Di Iulio, Arthur Wickenhagen, Alessandro Ceschi, Aoife M. Harbison, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Marco Schiuma, Malcolm G. Semple, Peter J.M. Openshaw, Elisa Fadda, J. Kenneth Baillie, John D. Chodera, The ISARIC4C Investigators, the COVID-19 Genomics UK (COG-UK) consortium, Suzannah J. Rihn, Samantha J. Lycett, Herbert W. Virgin, Amalio Telenti, Davide Corti, David L. Robertson, Gyorgy Snell

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26/01/2021 News
Covid-19: New UK variant may be linked to increased death rate, early ...

Covid-19: New UK variant may be linked to increased death rate, early data indicate

THE BMJ

Authors
Gareth Iacobucci

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25/01/2021 Report
Prospective mapping of viral mutations that escape antibodies used to ...

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

SCIENCE

Authors
Tyler N. Starr, Allison J. Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary, Adam S. Dingens, Jonathan Z. Li, Jesse D. Bloom

Abstract
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

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25/01/2021 Case Report
Prospective mapping of viral mutations that escape antibodies used to ...

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

SCIENCE

Authors
Tyler N. Starr, Allison J. Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary, Adam S. Dingens, Jonathan Z. Li, Jesse D. Bloom

Abstract
Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

Read More »

18/01/2021 News
Covid-19: What new variants are emerging and how are they being invest...

Covid-19: What new variants are emerging and how are they being investigated?

THE BMJ

Authors
Elisabeth Mahase

Read More »

15/01/2021 Articles
New coronavirus variants could cause more reinfections, require update...

New coronavirus variants could cause more reinfections, require updated vaccines

SCIENCE

Authors
Kai Kupferschmidt

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15/01/2021 Report
Learning the language of viral evolution and escape

SCIENCE

Authors
Brian Hie, Ellen D. Zhong, Bonnie Berger, Bryan Bryson

Abstract
The ability for viruses to mutate and evade the human immune system and cause infection, called viral escape, remains an obstacle to antiviral and vaccine development. Understanding the complex rules that govern escape could inform therapeutic design. We modeled viral escape with machine learning algorithms originally developed for human natural language. We identified escape mutations as those that preserve viral infectivity but cause a virus to look different to the immune system, akin to word changes that preserve a sentence’s grammaticality but change its meaning. With this approach, language models of influenza hemagglutinin, HIV-1 envelope glycoprotein (HIV Env), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike viral proteins can accurately predict structural escape patterns using sequence data alone. Our study represents a promising conceptual bridge between natural language and viral evolution.

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15/01/2021 Press Release
Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, ...

Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021

MMWR (MORBIDITY AND MORTALITY WEEKLY REPORT)

Authors
Summer E. Galloway, Prabasaj Paul, Duncan R. MacCannell, Michael A. Johansson, John T. Brooks, Adam MacNeil, Rachel B. Slayton, Suxiang Tong, Benjamin J. Silk, Gregory L. Armstrong, Matthew Biggerstaff, Vivien G. Dugan

Read More »

14/01/2021 Articles
ATP biphasically modulates LLPS of SARS-CoV-2 nucleocapsid protein and...

ATP biphasically modulates LLPS of SARS-CoV-2 nucleocapsid protein and specifically binds its RNA-binding domain

ELSEVIER

Authors
Mei Dang, Yifan Li, Jianxing Song

Abstract
SARS-CoV-2 is a highly contagious coronavirus causing the ongoing pandemic. Very recently its genomic RNA of ∼30 kb was decoded to be packaged with nucleocapsid (N) protein into phase separated condensates. Interestingly, viruses have no ability to generate ATP but host cells have very high ATP concentrations of 2–12 mM. A key question thus arises whether ATP modulates liquid-liquid phase separation (LLPS) of the N protein. Here we discovered that ATP not only biphasically modulates LLPS of the viral N protein as we previously found on human FUS and TDP-43, but also dissolves the droplets induced by oligonucleic acid. Residue-specific NMR characterization showed ATP specifically binds the RNA-binding domain (RBD) of the N protein with the average Kd of 3.3 ± 0.4 mM. The ATP-RBD complex structure was constructed by NMR-derived constraints, in which ATP occupies a pocket within the positive-charged surface utilized for binding nucleic acids. Our study suggests that ATP appears to be exploited by SARS-CoV-2 to promote its life cycle by facilitating the uncoating, localizing and packing of its genomic RNA. Therefore the interactions of ATP with the viral RNA and N protein might represent promising targets for design of drugs and vaccines to terminate the pandemic.

Read More »

12/01/2021 Correspondence
First detection of SARS-CoV-2 spike protein N501 mutation in Italy in ...

First detection of SARS-CoV-2 spike protein N501 mutation in Italy in August, 2020

THE LANCET

Authors
Simona Fiorentini, Serena Messali, Alberto Zani, Francesca Caccuri, Marta Giovanetti, Massimo Ciccozzi, Arnaldo Caruso

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08/01/2021 PERSPECTIVE
SARS-CoV-2 spillover events

SCIENCE

Authors
Peng Zhou, Zheng-Li Shi

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08/01/2021 Research
Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the U...

Establishment and lineage dynamics of the SARS-CoV-2 epidemic in the UK

SCIENCE

Authors
Louis du Plessis, John T. McCrone, Alexander E. Zarebski, Verity Hill, Christopher Ruis, Bernardo Gutierrez, Jayna Raghwani, Jordan Ashworth, Rachel Colquhoun, Thomas R. Connor, Nuno R. Faria, Ben Jackson, Nicholas J. Loman, Áine O’Toole, Samuel M. Nicholls, Kris V. Parag, Emily Scher, Tetyana I. Vasylyeva, Erik M. Volz, Alexander Watts, Isaac I. Bogoch, Kamran Khan, David M. Aanensen, Moritz U. G. Kraemer, Andrew Rambaut, Oliver G. Pybus

Abstract
The UK’s COVID-19 epidemic during early 2020 was one of world’s largest and unusually well represented by virus genomic sampling. Here we reveal the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 SARS-CoV-2 genomes, including 26,181 from the UK sampled throughout the country’s first wave of infection. Using large-scale phylogenetic analyses, combined with epidemiological and travel data, we quantify the size, spatio-temporal origins and persistence of genetically-distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, while lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.

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05/01/2021 Articles
New variant of SARS-CoV-2 in UK causes surge of COVID-19

THE LANCET

Authors
Tony Kirby

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31/12/2020 Articles
Estimated transmissibility and severity of novel SARS-CoV-2 Variant of...

Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

CMMID REPOSITORY

Authors
Nicholas Davies, Rosanna C Barnard, Christopher I Jarvis, Adam J Kucharski, James D Munday, Carl A.B. Pearson, Timothy W Russell, Damien C Tully, Sam Abbott, Amy Gimma, William Waites, Kerry LM Wong, Kevin van Zandvoort, Rosalind M Eggo, Sebastian Funk, Mark Jit, Katherine E Atkins, W John Edmunds

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29/12/2020 Risk Assestment
Risk related to spread of new SARS- CoV-2 variants of concern in the E...

Risk related to spread of new SARS- CoV-2 variants of concern in the EU/EEA

ECDC

Authors
EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL

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22/12/2020 Articles
Phylogenetic supertree reveals detailed evolution of SARS‐CoV‐2

NATURE

Authors
Tingting Li, Dongxia Liu, Yadi Yang, Jiali Guo, Yujie Feng, Xinmo Zhang, Shilong Cheng, Jie Feng

Abstract
Corona Virus Disease 2019 (COVID-19) caused by the emerged coronavirus SARS-CoV-2 is spreading globally. The origin of SARS-Cov-2 and its evolutionary relationship is still ambiguous. Several reports attempted to figure out this critical issue by genome-based phylogenetic analysis, yet limited progress was obtained, principally owing to the disability of these methods to reasonably integrate phylogenetic information from all genes of SARS-CoV-2. Supertree method based on multiple trees can produce the overall reasonable phylogenetic tree. However, the supertree method has been barely used for phylogenetic analysis of viruses. Here we applied the matrix representation with parsimony (MRP) pseudo-sequence supertree analysis to study the origin and evolution of SARS-CoV-2. Compared with other phylogenetic analysis methods, the supertree method showed more resolution power for phylogenetic analysis of coronaviruses. In particular, the MRP pseudo-sequence supertree analysis firmly disputes bat coronavirus RaTG13 be the last common ancestor of SARS-CoV-2, which was implied by other phylogenetic tree analysis based on viral genome sequences. Furthermore, the discovery of evolution and mutation in SARS-CoV-2 was achieved by MRP pseudo-sequence supertree analysis. Taken together, the MRP pseudo-sequence supertree provided more information on the SARS-CoV-2 evolution inference relative to the normal phylogenetic tree based on full-length genomic sequences.

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22/12/2020 Articles
Emergence and rapid spread of a new severe acute respiratory syndrome-...

Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa

MEDRXIV

Authors
Houriiyah Tegally, Eduan Wilkinson, Marta Giovanetti, Arash Iranzadeh, Vagner Fonseca, Jennifer Giandhari, Deelan Doolabh, Sureshnee Pillay, Emmanuel James San, Nokukhanya Msomi, Koleka Mlisana, Anne von Gottberg, Sibongile Walaza, Mushal Allam, Arshad Ismail, Thabo Mohale, Allison J Glass, Susan Engelbrecht, Gert Van Zyl, Wolfgang Preiser, Francesco Petruccione, Alex Sigal, Diana Hardie, Gert Marais, Marvin Hsiao, Stephen Korsman, Mary-Ann Davies, Lynn Tyers, Innocent Mudau, Denis York, Caroline Maslo, Dominique Goedhals, Shareef Abrahams, Oluwakemi Laguda-Akingba, Arghavan Alisoltani-Dehkordi, Adam Godzik, Constantinos Kurt Wibmer, Bryan Trevor Sewell, José Lourenço, Luiz Carlos Junior Alcantara, Sergei L Kosakovsky Pond, Steven Weaver, Darren Martin, Richard J Lessells, Jinal N Bhiman, Carolyn Williamson, Tulio de Oliveira

Summary
Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

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21/12/2020 Articles
Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from...

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland

NATURE

Authors
Ana da Silva Filipe, James G. Shepherd, Thomas Williams, Joseph Hughes, Elihu Aranday-Cortes, Patawee Asamaphan, Shirin Ashraf, Carlos Balcazar, Kirstyn Brunker, Alasdair Campbell, Stephen Carmichael, Chris Davis, Rebecca Dewar, Michael D. Gallagher, Rory Gunson, Verity Hill, Antonia Ho, Ben Jackson, Edward James, Natasha Jesudason, Natasha Johnson, E. Carol McWilliam Leitch, Kathy Li, Alasdair MacLean, Daniel Mair, David A. McAllister, John T. McCrone, Sarah E. McDonald, Martin P. McHugh, A. Keith Morris, Jenna Nichols, Marc Niebel, Kyriaki Nomikou, Richard J. Orton, Áine O’Toole, Massimo Palmarini, Benjamin J. Parcell, Yasmin A. Parr, Andrew Rambaut, Stefan Rooke, Sharif Shaaban, Rajiv Shah, Joshua B. Singer, Katherine Smollett, Igor Starinskij, Lily Tong, Vattipally B. Sreenu, Elizabeth Wastnedge, The COVID-19 Genomics UK (COG-UK) Consortium, Matthew T. G. Holden, David L. Robertson, Kate Templeton, Emma C. Thomson

Abstract
Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.

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21/12/2020 Research
Emergence of a Highly Fit SARS-CoV-2 Variant

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Ralph S. Baric, Elizabeth G. Phimister

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19/12/2020 Case Report
Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage...

Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

ARAMBAUT

Authors
Andrew Rambaut, Nick Loman, Oliver Pybus, Wendy Barclay, Jeff Barrett, Alesandro Carabelli, Tom Connor, Tom Peacock, David L Robertson, Erik Volz

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18/12/2020 Research
Susceptibility of Domestic Swine to Experimental Infection with Severe...

Susceptibility of Domestic Swine to Experimental Infection with Severe Acute Respiratory Syndrome Coronavirus 2

CDC (CENTERS FOR DISEASE CONTROL AND PREVENTION)

Authors
Brad S. Pickering, Greg Smith, Mathieu M. Pinette, Carissa Embury-Hyatt, Estella Moffat, Peter Marszal, Charles E. Lewis

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes coronavirus disease, has been shown to infect several species. The role of domestic livestock and associated risks for humans in close contact with food production animals remains unknown for many species. Determining the susceptibility of pigs to SARS-CoV-2 is critical to a One Health approach to manage potential risk for zoonotic transmission. We found that pigs are susceptible to SARS-CoV-2 after oronasal inoculation. Among 16 animals, we detected viral RNA in group oral fluids and in nasal wash from 2 pigs, but live virus was isolated from only 1 pig. Antibodies also were detected in only 2 animals at 11 and 13 days postinoculation but were detected in oral fluid samples at 6 days postinoculation, indicating antibody secretion. These data highlight the need for additional livestock assessment to determine the potential role of domestic animals in the SARS-CoV-2 pandemic.

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16/12/2020 News
Covid-19: New coronavirus variant is identified in UK

THE BMJ

Authors
Jacqui Wise

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04/12/2020 Articles
Evidence of exposure to SARS-CoV-2 in cats and dogs from households in...

Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy

NATURE

Authors
E. I. Patterson , G. Elia, A. Grassi, A. Giordano, C. Desario, M. Medardo, S. L. Smith, E. R. Anderson1 , T. Prince7, G. T. Patterson 6, E. Lorusso2, M. S. Lucente2, G. Lanave2, S. Lauzi, U. Bonfanti, A. Stranieri, V. Martella, F. Solari Basano, V. R. Barrs, A. D. Radford, U. Agrimi, G. L. Hughes, S. Paltrinieri, N. Decaro

Abstract
SARS-CoV-2 emerged from animals and is now easily transmitted between people. Sporadic detection of natural cases in animals alongside successful experimental infections of pets, such as cats, ferrets and dogs, raises questions about the susceptibility of animals under natural conditions of pet ownership. Here, we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households. Understanding risk factors associated with this and their potential to infect other species requires urgent investigation.

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19/11/2020 Articles
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of vi...

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

THE LANCET

Authors
Muge Cevik, Matthew Tate, Ollie Lloyd, Alberto Enrico Maraolo, Jenna Schafers, Antonia Ho

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18/11/2020 News
What the data say about asymptomatic COVID infections

NATURE

Authors
Bianca Nogrady

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13/11/2020 Articles
Functional importance of the D614G mutation in the SARS-CoV-2 spike pr...

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

ELSEVIER

Authors
Cody B.Jackson, Lizhou Zhang, Michael Farzan, Hyeryun Choe

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. Compared to the reference strain of SARS-CoV-2, the majority of currently circulating isolates possess an S protein variant characterized by an aspartic acid-to-glycine substitution at amino acid position 614 (D614G). Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2. This review summarizes and synthesizes the epidemiological and functional observations of the D614G spike mutation, with focus on the biochemical and cell-biological impact of this mutation and its consequences for S protein function. We further discuss the significance of these recent findings in the context of the current global pandemic.

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12/11/2020 Report
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and tr...

SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

SCIENCE

Authors
Yixuan J. Hou, Shiho Chiba, Peter Halfmann, Camille Ehre, Makoto Kuroda, Kenneth H. Dinnon III, Sarah R. Leist, Alexandra Schäfer, Noriko Nakajima, Kenta Takahashi, Rhianna E. Lee, Teresa M. Mascenik, Rachel Graham, Caitlin E. Edwards, Longping V. Tse, Kenichi Okuda, Alena J. Markmann, Luther Bartelt, Aravinda de Silva, David M. Margolis, Richard C. Boucher, Scott H. Randell, Tadaki Suzuki, Lisa E. Gralinski, Yoshihiro Kawaoka, Ralph S. Baric

Abstract
The spike D614G substitution is prevalent in global SARS-CoV-2 strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells, but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

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30/10/2020 PERSPECTIVE
Will SARS- CoV-2 become endemic?

SCIENCE

Authors
Jeffrey Shaman, Marta Galanti

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28/10/2020 Research
Escape from neutralizing antibodies by SARS-CoV-2 spike protein varian...

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

ELIFE

Authors
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio CC Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz

Abstract
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

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27/10/2020 Articles
Structural basis for potent neutralization of SARS-CoV-2 and role of a...

Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation

NATURE

Authors
Nicholas K. Hurlburt, Emilie Seydoux, Yu-Hsin Wan, Venkata Viswanadh Edara, Andrew B. Stuart, Junli Feng, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos, Marie Pancera

Abstract
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.

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27/10/2020 STUDY PROTOCOL
Coronavirus disease 2019 (COVID-19)

THE BMJ

Authors
Nicholas J. Beeching, Tom E. Fletcher, Robert Fowler, William A. Petri, Xin Zhang, Ran Nir-Paz

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26/10/2020 Articles
Spike mutation D614G alters SARS-CoV-2 fitness

NATURE

Authors
Jessica A. Plante, Yang Liu, Jianying Liu, Hongjie Xia, Bryan A. Johnson, Kumari G. Lokugamage, Xianwen Zhang, Antonio E. Muruato, Jing Zou, Camila R. Fontes-Garfias, Divya Mirchandani, Dionna Scharton, John P. Bilello, Zhiqiang Ku, Zhiqiang An, Birte Kalveram, Alexander N. Freiberg, Vineet D. Menachery, Xuping Xie, Kenneth S. Plante, Scott C. Weaver & Pei-Yong Shi

Abstract
A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic1,2. However, the impact on viral spread and vaccine efficacy remains to be defined. Here, we engineer the D614G mutation in the USA-WA1/2020 strain and characterize its effect. D614G enhances replication on human lung epithelial cells and primary human airway tissues through an improved infectivity of virions. Hamsters infected with the G614 variant produced higher infectious titers in the nasal washes and trachea, but not lungs, confirming clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. Sera from D614-infected hamsters exhibit modestly higher neutralization titers against G614 virus than against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

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23/10/2020 Analysis
Virology, transmission, and pathogenesis of SARS-CoV-2

THE BMJ

Authors
Muge Cevik, Krutika Kuppalli, Jason Kindrachuk, Malik Peiris

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15/10/2020 Articles
Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets...

Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols

MEDRXIV

Authors
Z. Chen, Niklas Bobrovitz, Zahra Premji, Marion Koopmans, David N. Fisman, Frank X. Gu

Abstract
A growing number of studies provide insight into how SARS-CoV-2 spreads1-7. Yet, many factors that characterize its transmissibility remain unclear, including mechanistic correlates of overdispersion, viral kinetics, the extent to which respiratory droplets and aerosols carry viable virus and the infectiousness of asymptomatic, presymptomatic and pediatric cases7. Here, we developed a comprehensive dataset of respiratory viral loads (rVLs) via systematic review and investigated these factors using meta-analyses and modeling. By comparing cases of COVID-19, SARS and influenza A(H1N1)pdm09, we found that heterogeneity in rVL was associated with overdispersion and facilitated the distinctions in individual variation in infectiousness among these emergent diseases. For COVID-19, case heterogeneity was broad throughout the infectious period, although rVL tended to peak at 1 day from symptom onset (DFSO) and be elevated for 1-5 DFSO. While most cases presented minimal risk, highly infectious ones could spread SARS-CoV-2 by talking, singing or breathing, which shed virions at comparable rates via droplets and aerosols. Coughing shed considerable quantities of virions, predominantly via droplets, and greatly increased the contagiousness of many symptomatic cases relative to asymptomatic ones. Asymptomatic and symptomatic infections showed similar likelihoods of expelling aerosols with SARS-CoV-2, as did adult and pediatric cases. Children tended to be less contagious by droplet spread than adults based on tendencies of symptomatology rather than rVL. Our findings address longstanding questions on SARS-CoV-2 transmissibility and present pertinent considerations for disease control.

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07/10/2020 Research
The effect of temperature on persistence of SARS-CoV-2 on common surfa...

The effect of temperature on persistence of SARS-CoV-2 on common surfaces

BMC

Authors
Shane Riddell, Sarah Goldie, Andrew Hill, Debbie Eagles, Trevor W. Drew

Abstract
Background
The rate at which COVID-19 has spread throughout the globe has been alarming. While the role of fomite transmission is not yet fully understood, precise data on the environmental stability of SARS-CoV-2 is required to determine the risks of fomite transmission from contaminated surfaces.

Methods
This study measured the survival rates of infectious SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on several common surface types. All experiments were carried out in the dark, to negate any effects of UV light. Inoculated surfaces were incubated at 20 °C, 30 °C and 40 °C and sampled at various time points.

Results
Survival rates of SARS-CoV-2 were determined at different temperatures and D-values, Z-values and half-life were calculated. We obtained half lives of between 1.7 and 2.7 days at 20 °C, reducing to a few hours when temperature was elevated to 40 °C. With initial viral loads broadly equivalent to the highest titres excreted by infectious patients, viable virus was isolated for up to 28 days at 20 °C from common surfaces such as glass, stainless steel and both paper and polymer banknotes. Conversely, infectious virus survived less than 24 h at 40 °C on some surfaces.

Conclusion
These findings demonstrate SARS-CoV-2 can remain infectious for significantly longer time periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19.

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29/09/2020 Articles
Viral epitope profiling of COVID-19 patients reveals cross-reactivity ...

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity

SCIENCE

Authors
Ellen Shrock, Eric Fujimura, Tomasz Kula, Richard T. Timms, I-Hsiu Lee4, Yumei Leng, Matthew L. Robinson5, Brandon M. Sie, Mamie Z. Li, Yuezhou Chen, Jennifer Logue, Adam Zuiani, Denise McCulloch, Felipe J. N. Lelis, Stephanie Henson, Daniel R. Monaco, Meghan Travers, Shaghayegh Habibi, William A. Clarke, Patrizio Caturegli, Oliver Laeyendecker, Alicja Piechocka-Trocha, Jon Li, Ashok Khatri, Helen Y. Chu6, MGH COVID-19 Collection & Processing Team, Alexandra-Chloé Villani, Kyle Kays, Marcia B. Goldberg, Nir Hacohen, Michael R. Filbin, Xu G. Yu, Bruce D. Walker, Duane R. Wesemann, H. Benjamin Larman, James A. Lederer, Stephen J. Elledge

Abstract
Understanding humoral responses to SARS-CoV-2 is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era controls using VirScan revealed over 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Pre-existing antibodies in controls recognized SARS-CoV-2 ORF1, while only COVID-19 patients primarily recognized spike and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of CMV and HSV-1, possibly influenced by demographic covariates. Among hospitalized patients, males make greater SARS-CoV-2 antibody responses than females.

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29/09/2020 Articles
High-resolution structures ofthe SARS-CoV-2 2′-O- methyltransferase re...

High-resolution structures ofthe SARS-CoV-2 2′-O- methyltransferase reveal strategies for structure-based inhibitor design

SCIENCE

Authors
Monica Rosas-Lemus, George Minasov, Ludmilla Shuvalova, Nicole L. Inniss, Olga Kiryukhina, Joseph Brunzelle, Karla J. F. Satchell

Abstract
There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2′-O-methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG). We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog m7GpppA and either SAM or SAH. Comparative analyses between these structures and published structures for nsp16 from other betacoronaviruses revealed flexible loops in open and closed conformations at the m7GpppA-binding pocket. Bound sulfates in several of the structures suggested the location of the ribonucleic acid backbone phosphates in the ribonucleotide-binding groove. Additional nucleotide-binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for the development of antiviral inhibitors.

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24/09/2020 Articles
COVID19: an announced pandemic

NATURE

Authors
Sara Platto, Tongtong Xue, Ernesto Carafoli

Abstract
A severe upper respiratory tract syndrome caused by the new coronavirus has now spread to the entire world as a highly contagious pandemic. The large scale explosion of the disease is conventionally traced back to January of this year in the Chinese province of Hubei, the wet markets of the principal city of Wuhan being assumed to have been the specific causative locus of the sudden explosion of the infection. A number of findings that are now coming to light show that this interpretation of the origin and history of the pandemic is overly simplified. A number of variants of the coronavirus would in principle have had the ability to initiate the pandemic well before January of this year. However, even if the COVID-19 had become, so to say, ready, conditions in the local environment would have had to prevail to induce the loss of the biodiversity’s “dilution effect” that kept the virus under control, favoring its spillover from its bat reservoir to the human target. In the absence of these appropriate conditions only abortive attempts to initiate the pandemic could possibly occur: a number of them did indeed occur in China, and probably elsewhere as well. These conditions were unfortunately present at the wet marked in Wuhan at the end of last year.

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21/09/2020 Articles
COVID-19 image classification using deep features and fractional-order...

COVID-19 image classification using deep features and fractional-order marine predators algorithm

NATURE

Authors
Ahmed T. Sahlol, Dalia Yousri, Ahmed A. Ewees, Mohammed A. A. Al-qaness, Robertas Damasevicius, Mohamed Abd Elaziz

Abstract
Currently, we witness the severe spread of the pandemic of the new Corona virus, COVID-19, which causes dangerous symptoms to humans and animals, its complications may lead to death. Although convolutional neural networks (CNNs) is considered the current state-of-the-art image classification technique, it needs massive computational cost for deployment and training. In this paper, we propose an improved hybrid classification approach for COVID-19 images by combining the strengths of CNNs (using a powerful architecture called Inception) to extract features and a swarm-based feature selection algorithm (Marine Predators Algorithm) to select the most relevant features. A combination of fractional-order and marine predators algorithm (FO-MPA) is considered an integration among a robust tool in mathematics named fractional-order calculus (FO). The proposed approach was evaluated on two public COVID-19 X-ray datasets which achieves both high performance and reduction of computational complexity. The two datasets consist of X-ray COVID-19 images by international Cardiothoracic radiologist, researchers and others published on Kaggle. The proposed approach selected successfully 130 and 86 out of 51 K features extracted by inception from dataset 1 and dataset 2, while improving classification accuracy at the same time. The results are the best achieved on these datasets when compared to a set of recent feature selection algorithms. By achieving 98.7%, 98.2% and 99.6%, 99% of classification accuracy and F-Score for dataset 1 and dataset 2, respectively, the proposed approach outperforms several CNNs and all recent works on COVID-19 images.

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17/09/2020 Articles
Receptor binding and priming of the spike protein of SARS-CoV-2 for me...

Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion

NATURE

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

Abstract
SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1–4, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus Spike glycoprotein, S5–7. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2 components that remain associated following cleavage8–10. Fusion activation following receptor binding is proposed to involve the exposure of a second proteolytic site (S2’), cleavage of which is required for the fusion peptide release11,12. We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. The ten structures describe ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of an S1 subdomain following ACE2 binding, that disrupts interactions with S2, notably involving Asp61413–15, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.

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11/09/2020 PERSPECTIVE
Coronavirus dons a new crown

SCIENCE

Authors
Nuruddin Unchwaniwala, Paul Ahlquist

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11/09/2020 Report
A molecular pore spans the double membrane of the coronavirus replicat...

A molecular pore spans the double membrane of the coronavirus replication organelle

SCIENCE

Authors
Georg Wolff, Ronald W. A. L. Limpens, Jessika C. Zevenhoven-Dobbe, Ulrike Laugks, Shawn Zheng, Anja W. M. de Jong, Roman I. Koning, David A. Agard, Kay Grünewald, Abraham J. Koster, Eric J. Snijder, Montserrat Bárcena1

Abstract
Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.

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11/09/2020 Articles
Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2...

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

NATURE

Authors
Jinsung Yang, Simon J. L. Petitjean, Melanie Koehler, Qingrong Zhang, Andra C. Dumitru, Wenzhang Chen, Sylvie Derclaye, Stéphane P. Vincent, Patrice Soumillion, David Alsteens

Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.

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03/09/2020 Original Research
Profiling and characterization of SARS-CoV-2 mutants’ infectivity and ...

Profiling and characterization of SARS-CoV-2 mutants’ infectivity and antigenicity

NATURE

Authors
Lin Wang, Ling Wang, Hui Zhuang

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03/09/2020 PERSPECTIVE
On Becoming a Plague Doctor

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors
Mark Earnest

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02/09/2020 Articles
Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 ...

Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques

NATURE

Authors
Wei Deng, Linlin Bao, Hong Gao, Zhiguang Xiang, Yajin Qu, Zhiqi Song, Shuran Gong, Jiayi Liu, Jiangning Liu, Pin Yu, Feifei Qi, Yanfeng Xu, Fengli Li, Chong Xiao, Qi Lv, Jing Xue, Qiang Wei, Mingya Liu, Guanpeng Wang, Shunyi Wang, Haisheng Yu, Ting Chen, Xing Liu, Wenjie Zhao, Yunlin Han, Chuan Qin

ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmitted through the respiratory route, but potential extra-respiratory routes of SARS-CoV-2 transmission remain uncertain. Here we inoculated five rhesus macaques with 1 × 106 TCID50 of SARS-CoV-2 conjunctivally (CJ), intratracheally (IT), and intragastrically (IG). Nasal and throat swabs collected from CJ and IT had detectable viral RNA at 1–7 days post-inoculation (dpi). Viral RNA was detected in anal swabs from only the IT group at 1–7 dpi. Viral RNA was undetectable in tested swabs and tissues after intragastric inoculation. The CJ infected animal had a higher viral load in the nasolacrimal system than the IT infected animal but also showed mild interstitial pneumonia, suggesting distinct virus distributions. This study shows that infection via the conjunctival route is possible in non-human primates; further studies are necessary to compare the relative risk and pathogenesis of infection through these different routes in more detail.

24/08/2020 Articles
Emerging of a SARS-CoV-2 viral strain with a deletion in nsp1

RESEARCH SQUARE

Authors
Francesca Benedetti Greg Snyder Marta Giovanetti Silvia Angeletti Massimo Ciccozzi Davide Zella


ABSTRACT
Background:
The new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first detected in Wuhan (China) in December of 2019 is responsible for the current global pandemic.
Phylogenetic analysis revealed that it is similar to other betacoronaviruses, such as SARS-CoV and Middle-Eastern Respiratory Syndrome, MERS-CoV. Its genome is ∼30 kb in length and contains two large overlapping polyproteins, ORF1a and ORF1ab that encode for several structural and non-structural proteins. The non-structural protein 1 (nsp1) is arguably the most important pathogenic determinant, and previous studies on SARS-CoV indicate that it is both involved in viral replication and hampering the innate immune system response. Detailed experiments of site-specific mutagenesis and in vitro reconstitution studies determined that the mechanisms of action are mediated by i) the presence of specific amino acid residues of nsp1 and b) the interaction between the protein and the host’s small ribosomal unit. In fact, substitution of certain amino acids resulted in reduction of its negative effects.
Methods: A total of 17928 genome sequences were obtained from the GISAID database (December 2019 to July 2020) from patients infected by SARS-CoV-2 from different areas around the world. Genomes alignment was performed using MAFFT (REFF) and the nsp1 genomic regions were identified using BioEdit and verified using BLAST. Nsp1 protein of SARS-CoV-2 with and without deletion have been subsequently modelled using I-TASSER.
Results: We identified SARS-CoV-2 genome sequences, from several Countries, carrying a previously unknown deletion of 9 nucleotides in position 686-694, corresponding to the AA position 241-243 (KSF). This deletion was found in different geographical areas. Structural prediction modelling suggests an effect on the C-terminal tail structure.
Conclusions: Modelling analysis of a newly identified deletion of 3 amino acids (KSF) of SARS-CoV-2 nsp1 suggests that this deletion could affect the structure of the C-terminal region of the protein, important for regulation of viral replication and negative effect on host’s gene expression. In addition, substitution of the two amino acids (KS) from nsp1 of SARS-CoV was previously reported to revert loss of interferon-alpha expression. The deletion that we describe indicates that SARS-CoV-2 is undergoing profound genomic changes. It is important to: i) confirm the spreading of this particular viral strain, and potentially of strains with other deletions in the nsp1 protein, both in the population of asymptomatic and pauci-symptomatic subjects, and ii) correlate these changes in nsp1 with potential decreased viral pathogenicity.

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23/08/2020 Reviews
Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and th...

Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development

ELSEVIER

Authors
Subodh Kumar, Samrata Anil, M.Tharappela, Zhong Lia, Hongmin Liab


ABSTRACT
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.

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20/08/2020 NEWSDESK
The origin of SARS-CoV-2

THE LANCET

Authors
Talha Burki


ABSTRACT
The recent outbreak of the betacoronavirus SARS-CoV-2 has become a significant concern to public health care worldwide. As of August 19, 2020, more than 22,140,472 people are infected, and over 781,135 people have died due to this deadly virus. In the USA alone, over 5,482,602 people are currently infected, and more than 171,823 people have died. SARS-CoV-2 has shown a higher infectivity rate and a more extended incubation period as compared to previous coronaviruses. SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2). Previously, several methods to develop a vaccine against SARS-CoV or MERS-CoV have been tried with limited success. Since SARS-CoV-2 uses the spike (S) protein for entry to the host cell, it is one of the most preferred targets for making vaccines or therapeutics against SARS-CoV-2. In this review, we have summarised the characteristics of the S protein, as well as the different approaches being used for the development of vaccines and/or therapeutics based on the S protein.

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18/08/2020 Letter
Peripheral immunophenotypes in children with multisystem inflammatory ...

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

NATURE

Authors
Michael J. Carter, Matthew Fish, Aislinn Jennings, Katie J. Doores, Paul Wellman, Jeffrey Seow, Sam Acors, Carl Graham, Emma Timms, Julia Kenny, Stuart Neil, Michael H. Malim, Shane M. Tibby, Manu Shankar-Hari


ABSTRACT
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1—multisystem inflammatory syndrome in children (MIS-C)—which comprises multiorgan dysfunction and systemic inflammation2,3,4,5,6,7,8,9,10,11,12,13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.

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18/08/2020 Research
Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cr...

Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak

PNAS

Authors
Tsuyoshi Sekizuka, Kentaro Itokawa, Tsutomu Kageyama, Shinji Saito, Ikuyo Takayama, Hideki Asanuma, Naganori Nao, Rina Tanaka, Masanori Hashino, View ORCID ProfileTakuri Takahashi, Hajime Kamiya, View ORCID ProfileTakuya Yamagishi, View ORCID ProfileKensaku Kakimoto, Motoi Suzuki, Hideki Hasegawa, Takaji Wakita, Makoto Kuroda


ABSTRACT
The Diamond Princess cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a coronavirus disease 2019 case. We performed whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from PCR+ clinical specimens and conducted a phylogenetic analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the Diamond Princess originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters could be linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network/phylogeny analysis in identifying potential infection routes. In late December 2019, an outbreak of a novel coronavirus disease 2019 (COVID-19) originated in Wuhan, China. It was caused by a new strain of betacoronavirus: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1, 2). The Diamond Princess (DP) cruise ship was put under quarantine soon after its return to Yokohama, Japan on February 3, 2020, after visiting Kagoshima, Hong Kong, Vietnam, Taiwan, and Okinawa, because an 80-y-old passenger who disembarked in Hong Kong was confirmed as a COVID-19 case on February 1 after the ship had departed from Hong Kong on January 25. The passenger presented with a cough beginning on January 23. From February 3 to 4 the health status of all passengers and crew members was investigated by quarantine officers and upper-respiratory specimens were collected from symptomatic passengers, crew, and their close contacts for SARS-CoV-2 PCR testing. As of February 5, there were a total of 3,711 individuals with 2,666 passengers and 1,045 crew members on board the DP. The Japanese government asked about 3,600 passengers and crew members to stay on board in Yokohama during the 14-d isolation period through February 19 to prevent the further spread of COVID-19 cases. A field epidemiological study about the DP COVID-19 cases has been published (3). As of March 8, 697 COVID-19 cases had been identified among the 3,711 persons on the DP and 7 people had died (4). Here, we have generated a haplotype network of the SARS-CoV-2 outbreak using genome-wide single nucleotide variations (SNVs), identifying the genotypes of isolates that disseminated in the DP cruise ship after quarantine on February 5, 2020.

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18/08/2020 Articles
Effects of a major deletion in the SARS-CoV-2 genome on the severity o...

Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study

THE LANCET

Authors
Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Chien Lye, Lisa F P Ng

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16/08/2020 Reviews
Biological fluid dynamics of airborne COVID-19 infection

SPRINGER LINK

Authors
Giovanni Seminara, Bruno Carli, Guido Forni, Sandro Fuzzi, Andrea Mazzino, Andrea Rinaldo

Abstract
We review the state of knowledge on the bio-fluid dynamic mechanisms involved in the transmission of the infection from SARS-CoV-2. The relevance of the subject stems from the key role of airborne virus transmission by viral particles released by an infected person via coughing, sneezing, speaking or simply breathing. Speech droplets generated by asymptomatic disease carriers are also considered for their viral load and potential for infection. Proper understanding of the mechanics of the complex processes whereby the two-phase flow emitted by an infected individual disperses into the environment would allow us to infer from first principles the practical rules to be imposed on social distancing and on the use of facial and eye protection, which to date have been adopted on a rather empirical basis. These measures need compelling scientific validation. A deeper understanding of the relevant biological fluid dynamics would also allow us to evaluate the contrasting effects of natural or forced ventilation of environments on the transmission of contagion: the risk decreases as the viral load is diluted by mixing effects but contagion is potentially allowed to reach larger distances from the infected source. To that end, our survey supports the view that a formal assessment of a number of open problems is needed. They are outlined in the discussion.

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13/08/2020 Editorial
A dangerous rush for vaccines

SCIENCE

Authors
H. Holden Thorp

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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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30/07/2020 Articles
Differential Tropism of SARS-CoV and SARS-CoV-2 in Bat Cells

CENTERS FOR DISEASE CONTROL AND PREVENTION

Authors
Susanna K.P. Lau1Comments to Author , Antonio C.P. Wong1, Hayes K.H. Luk1, Kenneth S.M. Li, Joshua Fung, Zirong He, Flora K.K. Cheng, Tony T.Y. Chan, Stella Chu, Kam Leng Aw-Yong, Terrence C.K. Lau, Kitty S.C. Fung, Patrick C.Y. Woo

Abstract
Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.

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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