SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo
Kenrie P Y Hui,John C. W. Ho,Man Chun Cheung,Ka Chun Ng,Rachel Hiu Ha Ching,Ka-ling Lai,T. Kam,Haogao Gu,Ko-Yung Sit,M. K. Hsin,Timmy W.K. Au,Leo L. M. Poon,Malik Peiris,John M. Nicholls,Michael C. W. Chan +14 more
Reads0
Chats0
TLDR
In this paper , the authors compared the replication competence and cellular tropism of the wild-type SARS-CoV-2 variants of concern with progressively increased transmissibility between humans, and found that Omicron is more dependent on TMPRSS2 and cathepsins for infection.Abstract:
The emergence of SARS-CoV-2 variants of concern with progressively increased transmissibility between humans is a threat to global public health. The Omicron variant of SARS-CoV-2 also evades immunity from natural infection or vaccines1, but it is unclear whether its exceptional transmissibility is due to immune evasion or intrinsic virological properties. Here we compared the replication competence and cellular tropism of the wild-type virus and the D614G, Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529) variants in ex vivo explant cultures of human bronchi and lungs. We also evaluated the dependence on TMPRSS2 and cathepsins for infection. We show that Omicron replicates faster than all other SARS-CoV-2 variants studied in the bronchi but less efficiently in the lung parenchyma. All variants of concern have similar cellular tropism compared to the wild type. Omicron is more dependent on cathepsins than the other variants of concern tested, suggesting that the Omicron variant enters cells through a different route compared with the other variants. The lower replication competence of Omicron in the human lungs may explain the reduced severity of Omicron that is now being reported in epidemiological studies, although determinants of severity are multifactorial. These findings provide important biological correlates to previous epidemiological observations. read more
Citations
More filters
Journal ArticleDOI
Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study
TL;DR: In this paper , the relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression, with higher reductions for more severe endpoints and significant variation with age.
Journal ArticleDOI
Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants
Hung Fu Tseng,Bradley Ackerson,Yi Luo,Lina S. Sy,Carla A. Talarico,Yun Tian,Katia Bruxvoort,Julia Tubert,Ana Florea,J.-H. Ku,Soon Kyu Choi,Harpreet S. Takhar,M. Aragones,Lei Qian +13 more
TL;DR: In this paper , a test-negative case-control study was conducted to evaluate mRNA-1273 vaccine effectiveness against infection and hospitalization with Omicron (B.1.529) variant.
Journal ArticleDOI
Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study
TL;DR: In this article , the authors collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App) to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population.
Posted ContentDOI
The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry
Thomas P. Peacock,Jonathan Brown,Jie-Nan Zhou,Nazia Thakur,Joseph Newman,Ruthiran Kugathasan,Ksenia Sukhova,Myrsini Kaforou,Dalan Bailey,Wendy S. Barclay +9 more
TL;DR: It is shown Omicron replicates rapidly in human primary airway cultures, more so even than the previously dominant variant of concern, Delta, and is posited to be more infectious at lower exposure doses, and resulting in enhanced intrinsic transmissibility.
Journal ArticleDOI
Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California
TL;DR: In this article , the authors show that Omicron variant infections were associated with substantially reduced risk of progression to severe clinical outcomes relative to time-matched Delta (B.1.2) variant infections within a large, integrated healthcare system in Southern California.
References
More filters
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
Beitrag zur kollektiven behandlung pharmakologischer reihenversuche
TL;DR: In this paper, ein Verfahren zur kollektiven behandlung von Reihenversuchen angegeben, das gestattet, bei kleinerem Umfang des Kollektivs (Reihenversuch mit vier bis funf Gruppen zu je sechs Tieren) and bei starker Streuung zu einem zahlenmasigen Ausdruck des Versuchsergebnisses zu gelangen.
Journal ArticleDOI
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.
Nicholas G Davies,Sam Abbott,Rosanna C. Barnard,Christopher I Jarvis,Adam J. Kucharski,James D Munday,Carl A. B. Pearson,Timothy W Russell,Damien C. Tully,Alex D. Washburne,Tom Wenseleers,Amy Gimma,William Waites,Kerry L. M. Wong,Kevin van Zandvoort,Justin D. Silverman,Karla Diaz-Ordaz,Ruth H. Keogh,Rosalind M Eggo,Sebastian Funk,Mark Jit,Katherine E. Atkins,Katherine E. Atkins,W. John Edmunds +23 more
TL;DR: Using a variety of statistical and dynamic modeling approaches, the authors estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants, and a fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases.
Journal ArticleDOI
Spike mutation D614G alters SARS-CoV-2 fitness.
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 +21 more
TL;DR: Hamsters infected with SARS-CoV-2 expressing spike D614G (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission.
Journal ArticleDOI
Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells
Shutoku Matsuyama,Naganori Nao,Kazuya Shirato,Miyuki Kawase,Shinji Saito,Ikuyo Takayama,Noriyo Nagata,Tsuyoshi Sekizuka,Hiroshi Katoh,Fumihiro Kato,Masafumi Sakata,Maino Tahara,Satoshi Kutsuna,Norio Ohmagari,Makoto Kuroda,Tadaki Suzuki,Tsutomu Kageyama,Makoto Takeda +17 more
TL;DR: It is shown that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to Sars-CoV-2 infection, making it useful for isolating and propagating SARS-Cov-2.