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SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells

View ORCID ProfileAvan Antia, View ORCID ProfileDavid M. Alvarado, Qiru Zeng, Deanna L. Davis, Matthew A. Ciorba, Siyuan Ding
doi: https://doi.org/10.1101/2022.04.13.487939
Avan Antia
1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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David M. Alvarado
2Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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Qiru Zeng
1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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Deanna L. Davis
2Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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Matthew A. Ciorba
2Inflammatory Bowel Diseases Center, Division of Gastroenterology, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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  • For correspondence: mciorba@wustl.edu siyuan.ding@wustl.edu
Siyuan Ding
1Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
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  • For correspondence: mciorba@wustl.edu siyuan.ding@wustl.edu
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Abstract

Omicron B.1.1.529 became the predominant SARS-CoV-2 variant in early 2022, causing a new wave of public anxiety. Compared to the ancestral strain, Omicron has 50 mutations, with over 30 mutations in the spike protein. These differences likely underlie the changes in Omicron biology noted in other studies, including an attenuation in the lung parenchyma, compared to the ancestral SARS-CoV-2 strain and other variants, as well as a preference for endosomal entry, in place of the TMPRSS2-mediated membrane fusion pathway. This raises questions on Omicron tropism and infectivity in various target organ systems, including the gastrointestinal (GI) tract. Up to 70% of COVID-19 patients report GI symptoms, including nausea, vomiting, and diarrhea. Here, we show that in the context of donor intrinsic genetic heterogeneity, the SARS-CoV-2 Omicron variant infects human colonoids similarly, if not less effectively, than the ancestral WT (WA1) strain or the Delta variant. Additionally, we note a higher ratio of viral RNA to infectious virus titer, which may suggest that Omicron is potentially less infectious in the intestine. This study lays the foundation for further work defining mechanisms mediating intestinal infection and pathogenesis by Omicron.

Competing Interest Statement

D.M.A., M.A.C, and S.D. received funding through investigator initiated sponsored research agreements from Pfizer (#61798927) and Janssen (NOPRODIBD0001).

Footnotes

  • Conflict of interest statement: D.M.A., M.A.C, and S.D. received funding through investigator initiated sponsored research agreements from Pfizer (#61798927) and Janssen (NOPRODIBD0001).

  • Funding: Washington University DDRCC (NIDDK P30 DK052574) and T32 fellowship (DK007130) (A.A.), CCF #648423 (D.M.A.), Philanthropic support from the Lawrence C. Pakula MD IBD Innovation Fund at Washington University and www.givinitallforguts.org (D.M.A, M.A.C), R01 DK109384 (M.A.C.), R56 AI167285 (M.A.C, S.D.), R01 AI150796 (S.D.).

  • All data, analytic methods, and study materials will be made available to other researchers upon request.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 14, 2022.
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SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells
Avan Antia, David M. Alvarado, Qiru Zeng, Deanna L. Davis, Matthew A. Ciorba, Siyuan Ding
bioRxiv 2022.04.13.487939; doi: https://doi.org/10.1101/2022.04.13.487939
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SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells
Avan Antia, David M. Alvarado, Qiru Zeng, Deanna L. Davis, Matthew A. Ciorba, Siyuan Ding
bioRxiv 2022.04.13.487939; doi: https://doi.org/10.1101/2022.04.13.487939

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