TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes.
Ruochen Zang,Ruochen Zang,Maria Florencia Gomez Castro,Broc T. McCune,Qiru Zeng,Paul W. Rothlauf,Paul W. Rothlauf,Naomi M. Sonnek,Zhuoming Liu,Kevin Brulois,Kevin Brulois,Xin Wang,Harry B. Greenberg,Harry B. Greenberg,Michael S. Diamond,Matthew A. Ciorba,Sean P. J. Whelan,Siyuan Ding +17 more
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TLDR
In this article, the authors reported productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids, which may contribute to local and systemic illness and overall disease progression.Abstract:
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients. However, it is unclear whether SARS-CoV-2 replicates in the human intestine and contributes to possible fecal-oral transmission. Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells. We also demonstrate that viruses released into the intestinal lumen were inactivated by simulated human colonic fluid, and infectious virus was not recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression.read more
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Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.
Bette T. Korber,Will Fischer,Sandrasegaram Gnanakaran,Hyejin Yoon,James Theiler,Werner Abfalterer,Nick Hengartner,Elena E. Giorgi,Tanmoy Bhattacharya,Brian T. Foley,Kathryn M. Hastie,Matthew Parker,David G Partridge,Cariad Evans,Timothy M. Freeman,Thushan I de Silva,Adrienne Angyal,Rebecca Brown,Laura Carrilero,Luke R. Green,Luke R. Green,Luke R. Green,Danielle C. Groves,Katie Johnson,Alexander J Keeley,Benjamin B Lindsey,Paul J. Parsons,Mohammad Raza,Sarah Rowland-Jones,Nikki Smith,Rachel Tucker,Dennis Wang,Matthew Wyles,Charlene McDanal,Lautaro G. Perez,Haili Tang,Alex Moon-Walker,Alex Moon-Walker,Alex Moon-Walker,Sean P. J. Whelan,Celia C. LaBranche,Erica Ollmann Saphire,David C. Montefiori +42 more
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
Journal ArticleDOI
Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies.
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,Davide Corti,Herbert W. Virgin,Herbert W. Virgin,Ali H. Ellebedy,Pei Yong Shi,Michael S. Diamond +32 more
TL;DR: In this article, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, the authors report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants.
Journal ArticleDOI
Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
Zhuoming Liu,Laura A. VanBlargan,Louis Marie Bloyet,Paul W. Rothlauf,Paul W. Rothlauf,Rita E. Chen,Spencer Stumpf,Haiyan Zhao,John M. Errico,Elitza S. Theel,Mariel J. Liebeskind,Brynn Alford,William Buchser,Ali H. Ellebedy,Daved H. Fremont,Michael S. Diamond,Sean P. J. Whelan +16 more
TL;DR: In this article, a VSV-eGFP-SARS-CoV-2-S chimeric virus was exposed to 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) and generated 50 different escape mutants.
Journal ArticleDOI
Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.
TL;DR: In this paper, a review of the literature on long COVID-19 syndrome is presented, which is driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (i.e. from viral persistence, immune dysregulation, and autoimmunity).
Journal ArticleDOI
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies
Laura A. VanBlargan,John M. Errico,Peter Halfmann,Seth J. Zost,James E. Crowe,Lisa A. Purcell,Yoshihiro Kawaoka,Davide Corti,Daved H. Fremont,Michael S. Diamond +9 more
TL;DR: In this paper , the authors tested a panel of anti-receptor-binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309), the parent mAb of VIR-7831 (sotrovimab)), AstraZeneca (COV2-2196 and COV22130, the parentmAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Eli Lilly (LY-CoV555 and LY-Cov016) and Celltrion (CT-P59) for their ability to neutralize an infectious B.1.1-Omicron isolate.
References
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TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Journal ArticleDOI
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Nanshan Chen,Min Zhou,Xuan Dong,Jie-Ming Qu,Fengyun Gong,Yang Han,Yang Qiu,Jingli Wang,Ying Liu,Yuan Wei,Jia'an Xia,Ting Yu,Xinxin Zhang,Li Zhang +13 more
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
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