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High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection

Author

Listed:
  • Erica Normandin

    (Broad Institute of Harvard and MIT
    Harvard Medical School)

  • Melissa Rudy

    (Broad Institute of Harvard and MIT)

  • Nikolaos Barkas

    (Broad Institute of Harvard and MIT)

  • Stephen F. Schaffner

    (Broad Institute of Harvard and MIT)

  • Zoe Levine

    (Broad Institute of Harvard and MIT
    Harvard Medical School)

  • Robert F. Padera

    (Brigham and Women’s Hospital)

  • Mehrtash Babadi

    (Broad Institute of Harvard and MIT)

  • Shibani S. Mukerji

    (Massachusetts General Hospital)

  • Daniel J. Park

    (Broad Institute of Harvard and MIT)

  • Bronwyn L. MacInnis

    (Broad Institute of Harvard and MIT
    Harvard T. H. Chan School of Public Health, Harvard University
    Massachusetts Consortium on Pathogen Readiness)

  • Katherine J. Siddle

    (Broad Institute of Harvard and MIT
    Harvard Medical School)

  • Pardis C. Sabeti

    (Broad Institute of Harvard and MIT
    Harvard T. H. Chan School of Public Health, Harvard University
    Massachusetts Consortium on Pathogen Readiness
    Howard Hughes Medical Institute)

  • Isaac H. Solomon

    (Brigham and Women’s Hospital)

Abstract

SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects. The majority of the 180 viral variants identified within subjects are unique to individual tissue samples. We find more high-frequency (>10%) minor variants in subjects with a longer disease course, with one subject harboring ten such variants, exclusively in extrapulmonary tissues. One tissue-specific high-frequency variant was a nonsynonymous mutation in the furin-cleavage site of the spike protein. Our findings suggest adaptation and/or compartmentalized infection, illuminating the basis of extrapulmonary COVID-19 symptoms and potential for viral reservoirs, and have broad utility for investigating human pathogens.

Suggested Citation

  • Erica Normandin & Melissa Rudy & Nikolaos Barkas & Stephen F. Schaffner & Zoe Levine & Robert F. Padera & Mehrtash Babadi & Shibani S. Mukerji & Daniel J. Park & Bronwyn L. MacInnis & Katherine J. Sid, 2023. "High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-34256-y
    DOI: 10.1038/s41467-022-34256-y
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