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Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection

Mireille Farjo, Katia Koelle, Michael A. Martin, Laura L. Gibson, Kimberly K.O. Walden, Gloria Rendon, Christopher J. Fields, Fadi G. Alnaji, Nicholas Gallagher, Chun Huai Luo, Heba H. Mostafa, Yukari C. Manabe, View ORCID ProfileAndrew Pekosz, Rebecca L. Smith, David D. McManus, View ORCID ProfileChristopher B. Brooke
doi: https://doi.org/10.1101/2022.06.21.497047
Mireille Farjo
1Department of Microbiology, University of Illinois at Urbana-Champaign
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Katia Koelle
2Department of Biology, Emory University
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Michael A. Martin
2Department of Biology, Emory University
3Population Biology, Ecology, and Evolution Graduate Program, Emory University
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Laura L. Gibson
4Division of Infectious Diseases and Immunology, Departments of Medicine and Pediatrics, University of Massachusetts Medical School
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Kimberly K.O. Walden
5High-Performance Biological Computing at the Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign
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Gloria Rendon
5High-Performance Biological Computing at the Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign
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Christopher J. Fields
5High-Performance Biological Computing at the Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign
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Fadi G. Alnaji
1Department of Microbiology, University of Illinois at Urbana-Champaign
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Nicholas Gallagher
6Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine
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Chun Huai Luo
6Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine
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Heba H. Mostafa
6Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine
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Yukari C. Manabe
7Division of Infectious Disease, Department of Medicine, Johns Hopkins School of Medicine
8W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health
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Andrew Pekosz
8W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health
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  • ORCID record for Andrew Pekosz
Rebecca L. Smith
9Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign
10Department of Pathobiology, University of Illinois at Urbana-Champaign
11Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign
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David D. McManus
12Division of Cardiology, University of Massachusetts Medical School
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Christopher B. Brooke
1Department of Microbiology, University of Illinois at Urbana-Champaign
9Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign
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  • ORCID record for Christopher B. Brooke
  • For correspondence: cbrooke@illinois.edu
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Abstract

The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we deep sequenced saliva and nasal samples collected daily from immune and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both naive and immune individuals appeared largely stochastic; however, we identified clear mutational hotspots within the viral genome, consistent with selection and differing between naive and immune individuals. In rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of virus between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Added supplemental table with acknowledgment of sources of GISAID sequence data used. Corrected some references, typos, and added a missing author affiliation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 23, 2022.
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Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection
Mireille Farjo, Katia Koelle, Michael A. Martin, Laura L. Gibson, Kimberly K.O. Walden, Gloria Rendon, Christopher J. Fields, Fadi G. Alnaji, Nicholas Gallagher, Chun Huai Luo, Heba H. Mostafa, Yukari C. Manabe, Andrew Pekosz, Rebecca L. Smith, David D. McManus, Christopher B. Brooke
bioRxiv 2022.06.21.497047; doi: https://doi.org/10.1101/2022.06.21.497047
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Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection
Mireille Farjo, Katia Koelle, Michael A. Martin, Laura L. Gibson, Kimberly K.O. Walden, Gloria Rendon, Christopher J. Fields, Fadi G. Alnaji, Nicholas Gallagher, Chun Huai Luo, Heba H. Mostafa, Yukari C. Manabe, Andrew Pekosz, Rebecca L. Smith, David D. McManus, Christopher B. Brooke
bioRxiv 2022.06.21.497047; doi: https://doi.org/10.1101/2022.06.21.497047

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