COVID-19 / SARS-CoV-2 preprints

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin

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

https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2

Reports the identification and characterization of (nCoV-2019). Full-length genome sequences were obtained from patients, and were found to share 79.5% sequence identify to SARS-CoV, and to be 96% identical at the whole genome level to a bat coronavirus. Study confirmed that virus uses the same cell entry receptor, ACE2, as SARS-CoV.

Pattern of early human-to-human transmission of Wuhan 2019-nCoV

Julien Riou, Christian L. Althaus

https://www.biorxiv.org/content/10.1101/2020.01.23.917351v1

Reports stochastic simulations of early outbreak trajectories. Found that transmission characteristics were similar in magnitude to SARS-CoV and the 1918 pandemic influenza. Underlied importance of surveillance and early control.

Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

D. Paraskevis, E.G. Kostaki, G. Magiorkinis, G. Panayiotakopoulos, S. Tsiodras

https://www.biorxiv.org/content/10.1101/2020.01.26.920249v1

The analysis suggests that the 2019-nCoV shows discordant clustering with the Bat-SARS-like coronavirus sequences. Almost half of the virus’ genome is of a distinct lineage within the betacoronavirus.

Beware of asymptomatic transmission: Study on 2019-nCoV prevention and control measures based on extended SEIR model

Peng Shao, Yingji Shan

https://www.biorxiv.org/content/10.1101/2020.01.28.923169v1

Based on model studying the movement of people, this study is among first suggesting importance of testing, given role of assymptomatic transmission

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

Xiaolong Tian, Cheng Li, Ailing Huang, Shuai Xia, Sicong Lu, Zhengli Shi, Lu Lu, Shibo Jiang, Zhenlin Yang, Yanling Wu, Tianlei Ying

https://www.biorxiv.org/content/10.1101/2020.01.28.923011v1

Study found that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD, and proposes CR3022 as a potential candidate for therapeutics. The study emphasizes that various other antibodies that successfully neutralize SARS-CoV, fail to neutralize 2019-nCoV.

The incubation period of 2019-nCoV infections among travellers from Wuhan, China

Jantien A. Backer, Don Klinkenberg, Jacco Wallinga

https://www.medrxiv.org/content/10.1101/2020.01.27.20018986v2

Using the travel history of cases detected outside Wuhan, authors first estimated the mean incubation period to be 6.4 days, ranging from 2.1 to 11.1 days. They first suggested using these values for case definition.

Evolution and variation of 2019-novel coronavirus

Chenglong Xiong, Lufang Jiang, Yue Chen, Qingwu Jiang

https://www.biorxiv.org/content/10.1101/2020.01.30.926477v1

The study found a viral isolate different from other 2019-nCoVs, and suggests at least two different viral strains of 2019-nCoV are involved in the outbreak.

The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

Markus Hoffmann, Hannah Kleine-Weber, Nadine Krüger, Marcel Müller, Christian Drosten, Stefan Pöhlmann

https://www.biorxiv.org/content/10.1101/2020.01.31.929042v1.full

SARS-CoV-2 enters cells via SARS-coronavirus receptor, ACE2, and cellular protease TMPRSS2. TMPRSS2 inhibitor and serum from convalescent SARS patient prevented entry of SARS-CoV-2. This highlights the similarities between SARS-CoV-2 and SARS-coronavirus infections and could identify a potential target for antiviral intervention.

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

Hao Zhang, Zijian Kang, Haiyi Gong, Da Xu, Jing Wang, Zifu Li, Xingang Cui, Jianru Xiao, Tong Meng, Wang Zhou, Jianmin Liu, Huji Xu

https://www.biorxiv.org/content/10.1101/2020.01.30.927806v1

The work evaluated single-cell transcriptomes of lung, esophagus, gastric, ileum and colon. The data showed that apart from being highly expressed in organs of the respiratory tract, ACE2 (which acts as receptor for the virus) was also highly expressed in absorptive enterocytes from ileum and colon. These results indicated the digestive system as another potential route for 2019-nCov infection.

Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China

Fan Wu, Su Zhao, Bin Yu, Yan-Mei Chen, Wen Wang, Yi Hu, Zhi-Gang Song, Zhao-Wu Tao, Jun-Hua Tian, Yuan-Yuan Pei, Ming-Li Yuan, Yu-Ling Zhang, Fa-Hui Dai, Yi Liu, Qi-Min Wang, Jiao-Jiao Zheng, Lin Xu, Edward C. Holmes, Yong-Zhen Zhang

https://www.biorxiv.org/content/10.1101/2020.01.24.919183v2

Bronchoalveolar lavage was collected from 7 workers at the Wuhan seafood market. Next generation metagenomic RNA sequencing identified an RNA virus of family Coronaviridae, called at the time WH-Human-1 coronavirus. Phylogenetic analyis showed 89.1% similarity to SARS-like coronaviruses previously sampled from bats in China.

Estimated effectiveness of traveller screening to prevent international spread of 2019 novel coronavirus (2019-nCoV)

Katelyn Gostic, Ana C. R. Gomez, Riley O. Mummah, Adam J. Kucharski, James O. Lloyd-Smith

https://www.medrxiv.org/content/10.1101/2020.01.28.20019224v2

he study analyzes the impact of travel screening programs on coronavirus spread. They make a model available for interactive use. They estimate that around half of infected travelers will be missed by screening programs, but predict these cases will be those that have not yet developed symptoms and are unaware of exposure.

Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig

Changhai Lei, Wenyan Fu, Kewen Qian, Tian Li, Sheng Zhang, Min Ding, Shi Hu

https://www.biorxiv.org/content/10.1101/2020.02.01.929976v2

The study generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. Fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro.

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

Xiaoqiang Chai, Longfei Hu, Yan Zhang, Weiyu Han, Zhou Lu, Aiwu Ke, Jian Zhou, Guoming Shi, Nan Fang, Jia Fan, Jiabin Cai, Jue Fan, Fei Lan

https://www.biorxiv.org/content/10.1101/2020.02.03.931766v1

Describes that a proportion of SARS and 2019-nCoV patients showed signs of liver damage. The study found specific expression of ACE2 in cholangiocytes (epithelial cells of the bile duct), and suggests that the liver damage observed in some infected patients might be due to cholangiocyte dysfunction. The authors suggest addressing potential liver dysfunction in patients during and after hospital care.

Preparedness and vulnerability of African countries against introductions of 2019-nCoV

Marius Gilbert, Giulia Pullano, Francesco Pinotti, Eugenio Valdano, Chiara Poletto, Pierre-Yves Boelle, Eric D'Ortenzio, Yazdan Yazdanpanah, Serge Paul Eholie, Mathias Altmann, Bernardo Gutierrez, Moritz U. G. Kraemer, Vittoria Colizza

https://www.medrxiv.org/content/10.1101/2020.02.05.20020792v1

This study evaluated the preparedness and vulnerability of African countries against the risk of importation of 2019-nCoV based on travel volumes from infected provinces in China to African countries. Identified Egypt, Algeria, and South Africa ashaving the highest importation risk. Identified Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya as being at moderate risk, but as having high vulnerability. Suggests intensifying surveillance, and prioritizing capacity building.

A database resource for Genome-wide dynamics analysis of Coronaviruses on a historical and global scale

Zhenglin Zhu, Kaiwen Meng, Geng Meng

https://www.biorxiv.org/content/10.1101/2020.02.05.920009v1

This work developed a coronavirus database (CoVdb)- an online genomics and proteomics analysis platform. The database annotates the genome of every strain and identifies 780 possible ORFs of all strains available in Genebank. It also provides population genetics analysis, functional analysis and structural analysis on a historical and global scale. Accessed freely at http://covdb.popgenetics.net.

The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated

Steven Sanche, Yen Ting Lin, Chonggang Xu, Ethan Romero-Severson, Nick Hengartner, Ruian Ke

https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1

Initially, the basic reproductive number (R0) was estimated to be 2.2 to 2.7. This study integrates new estimates and high-resolution real-time human travel and infection data with mathematical models, and re-estimates the R0 value as being between 4.7 and 6.6.

Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)

Suxin Wan, Qingjie Yi, Shibing Fan, Jinglong Lv, Xianxiang Zhang, Lian Guo, Chunhui Lang, Qing Xiao, Kaihu Xiao, Zhengjun Yi, Mao Qiang, Jianglin Xiang, Bangshuo Zhang, Yongping Chen

https://www.medrxiv.org/content/10.1101/2020.02.10.20021832v1

Time-varying transmission dynamics of Novel Coronavirus Pneumonia in China

Tao Liu, Jianxiong Hu, Jianpeng Xiao, Guanhao He, Min Kang, Zuhua Rong, Lifeng Lin, Haojie Zhong, Qiong Huang, Aiping Deng, Weilin Zeng, Xiaohua Tan, Siqing Zeng, Zhihua Zhu, Jiansen Li, Dexin Gong, Donghua Wan, Shaowei Chen, Lingchuan Guo, Yan Li, Limei Sun, Wenjia Liang, Tie Song, Jianfeng He, Wenjun Ma

https://www.biorxiv.org/content/10.1101/2020.01.25.919787v2

Proposed that novel coronavirus has higher transmissibility than SARS between humans.

Diarrhea may be underestimated: a missing link in 2019 novel coronavirus

Weicheng Liang, Zhijie Feng, Shitao Rao, Cuicui Xiao, Zexiao Lin, Qi Zhang, Wei Qi

https://www.medrxiv.org/content/10.1101/2020.02.03.20020289v2

The authors suggest that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection, and that diarrhea may serve as an indicator for infection. They suggest that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.

The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice

Linlin Bao, Wei Deng, Baoying Huang, Hong Gao, Jiangning Liu, Lili Ren, Qiang Wei, Pin Yu, Yanfeng Xu, Feifei Qi, Yajin Qu, Fengdi Li, Qi Lv, Wenling Wang, Jing Xue, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Linna Zhao, Peipei Liu, Li Zhao, Fei Ye, Huijuan Wang, Weimin Zhou, Na Zhu, Wei Zhen, Haisheng Yu, Xiaojuan Zhang, Li Guo, Lan Chen, Conghui Wang, Ying Wang, Xinming Wang, Yan Xiao, Qiangming Sun, Hongqi Liu, Fanli Zhu, Chunxia Ma, Lingmei Yan, Mengli Yang, Jun Han, Wenbo Xu, Wenjie Tan, Xiaozhong Peng, Qi Jin, Guizhen Wu, Chuan Qin

https://www.biorxiv.org/content/10.1101/2020.02.07.939389v3

he study used hACE2 transgenic mice to study the pathogenicity of SARS-CoV-2. They define histopathology in the lungs, specific to transgenice mice and not observed in wild type mice. They propose this mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.

A human monoclonal antibody blocking SARS-CoV-2 infection

Chunyan Wang, Wentao Li, Dubravka Drabek, Nisreen M.A. Okba, Rien van Haperen, Albert D.M.E. Osterhaus, Frank J.M. van Kuppeveld, Bart L. Haagmans, Frank Grosveld, Berend-Jan Bosch

https://www.biorxiv.org/content/10.1101/2020.03.11.987958v1

Report of a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.

Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial

Philippe GAUTRET, Jean Christophe LAGIER, Philippe PAROLA, Van Thuan HOANG, Line MEDDED, Morgan MAILHE, Barbara DOUDIER, Johan COURJON, Valerie GIORDANENGO, Vera ESTEVES VIEIRA, Herve TISSOT DUPONT, Stephane HONORE, Philippe COLSON, Eric CHABRIERE, Bernard LA SCOLA, Jean Marc ROLAIN, Philippe BROUQUI, Didier RAOULT Sr.

https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v1

This preprint was the first to describe the use of Hydroxychloroquine and Azithromycin to treat COVID-19. It appeared in the journal International Journal of Antimicrobial Agents a day after it was submitted. 42 COVID-19 positive patients were enrolled in this study, 16 of which recieved normal care (control) and 26 receiving the Hydroxychloroquine therapy. Out of these 26, 20 completed the study with 6 of these patients also recieving Azithromycin (antibiotic). At day 6 of treatment, 100% of patients recieving the combination therapy were COVID-19 negative with approximately 50% of the Hydroxychloroquine-only group being COVID-19 negative. In contrast, most of the control were COVID-19 positive. Importantly, this was not a randomised clinical trial and there were numerous issues with the study and the subsequent “peer review” prior to publication. These are outlined fully by Dr Elizabeth Bik (https://scienceintegritydigest.com/2020/03/24/thoughts-on-the-gautret-et-al-paper-about-hydroxychloroquine-and-azithromycin-treatment-of-covid-19-infections/).

Reinfection could not occur in SARS-CoV-2 infected rhesus macaques

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

https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1

Rhesus macaques previously infected with SARS-CoV-2 could not be reinfected with virus within a period of 28 days after symptoms were alleviated. Conclusions highly exploratory and based on preliminary data gathered from 4 rhesus macaques.

Temporal dynamics in viral shedding and transmissibility of COVID-19

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

https://www.medrxiv.org/content/10.1101/2020.03.15.20036707v2

Models suggest that COVID-19 Infectiousness peaks at or before symptom onset, and 44% of transmissions could happen before symptom onset.

SARS-CoV-2 specific antibody responses in COVID-19 patients

NISREEN M.A. OKBA, Marcel A Muller, Wentao Li, Chunyan Wang, Corine H. GeurtsvanKessel, Victor M. Corman, Mart M. Lamers, Reina S. Sikkema, Erwin de Bruin, Felicity D. Chandler, Yazdan Yazdanpanah, Quentin Le Hingrat, Diane Descamps, Nadhira Houhou-Fidouh, Chantal B. E. M. Reusken, Berend-Jan Bosch, Christian Drosten, Marion P.G. Koopmans, Bart L. Haagmans

https://www.medrxiv.org/content/10.1101/2020.03.18.20038059v1

Confirming S1 as specific antigen for SARS-CoV-2 testing, relative to S2 antigen.

Analysis of codon usage and evolutionary rates of the 2019-nCoV genes

Maddalena Dilucca, Athanasia Pavlopoulou

https://www.biorxiv.org/content/10.1101/2020.03.25.006569v1

Main results suggest that the higher evolutionary rate observed for genes encoding nucleocapsid, viral replicase and spike proteins, could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Wenqi Shen, Ying Shi, Ziyang Zhang, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Christopher J.P. Mathy, Tina Perica, Kala B. Pilla

https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3