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SARS-CoV-2 infection and persistence in the human body and brain at autopsy

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  • Sydney R. Stein

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Sabrina C. Ramelli

    (Clinical Center, National Institutes of Health)

  • Alison Grazioli

    (Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health)

  • Joon-Yong Chung

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Manmeet Singh

    (Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Claude Kwe Yinda

    (Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Clayton W. Winkler

    (Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Junfeng Sun

    (Clinical Center, National Institutes of Health)

  • James M. Dickey

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Kris Ylaya

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Sung Hee Ko

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Andrew P. Platt

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Peter D. Burbelo

    (National Institute of Dental and Craniofacial Research, National Institutes of Health)

  • Martha Quezado

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Stefania Pittaluga

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Madeleine Purcell

    (University of Maryland School of Medicine)

  • Vincent J. Munster

    (Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Frida Belinky

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Marcos J. Ramos-Benitez

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, National Institutes of Health)

  • Eli A. Boritz

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Izabella A. Lach

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Daniel L. Herr

    (University of Maryland School of Medicine)

  • Joseph Rabin

    (University of Maryland School of Medicine)

  • Kapil K. Saharia

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Ronson J. Madathil

    (University of Maryland School of Medicine)

  • Ali Tabatabai

    (University of Maryland School of Medicine)

  • Shahabuddin Soherwardi

    (TidalHealth Peninsula Regional)

  • Michael T. McCurdy

    (University of Maryland School of Medicine
    University of Maryland St. Joseph Medical Center)

  • Karin E. Peterson

    (Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Jeffrey I. Cohen

    (Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Emmie Wit

    (Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health)

  • Kevin M. Vannella

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Stephen M. Hewitt

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • David E. Kleiner

    (Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Daniel S. Chertow

    (Clinical Center, National Institutes of Health
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Abstract

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1–3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6–14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.

Suggested Citation

  • Sydney R. Stein & Sabrina C. Ramelli & Alison Grazioli & Joon-Yong Chung & Manmeet Singh & Claude Kwe Yinda & Clayton W. Winkler & Junfeng Sun & James M. Dickey & Kris Ylaya & Sung Hee Ko & Andrew P. , 2022. "SARS-CoV-2 infection and persistence in the human body and brain at autopsy," Nature, Nature, vol. 612(7941), pages 758-763, December.
  • Handle: RePEc:nat:nature:v:612:y:2022:i:7941:d:10.1038_s41586-022-05542-y
    DOI: 10.1038/s41586-022-05542-y
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    Citations

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    Cited by:

    1. Noel G. Panagiotides & Fritz Zimprich & Klaus Machold & Oliver Schlager & Markus Müller & Sebastian Ertl & Henriette Löffler-Stastka & Renate Koppensteiner & Patricia P. Wadowski, 2023. "A Case of Autoimmune Small Fiber Neuropathy as Possible Post COVID Sequelae," IJERPH, MDPI, vol. 20(6), pages 1-12, March.
    2. S. Jaumdally & M. Tomasicchio & A. Pooran & A. Esmail & A. Kotze & S. Meier & L. Wilson & S. Oelofse & C. Merwe & A. Roomaney & M. Davids & T. Suliman & R. Joseph & T. Perumal & A. Scott & M. Shaw & W, 2024. "Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Scott Lu & Michael J. Peluso & David V. Glidden & Michelle C. Davidson & Kara Lugtu & Jesus Pineda-Ramirez & Michel Tassetto & Miguel Garcia-Knight & Amethyst Zhang & Sarah A. Goldberg & Jessica Y. Ch, 2024. "Early biological markers of post-acute sequelae of SARS-CoV-2 infection," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    4. Sung Hee Ko & Pierce Radecki & Frida Belinky & Jinal N. Bhiman & Susan Meiring & Jackie Kleynhans & Daniel Amoako & Vanessa Guerra Canedo & Margaret Lucas & Dikeledi Kekana & Neil Martinson & Limakats, 2024. "Rapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Clovis S. Palmer & Chrysostomos Perdios & Mohamed Abdel-Mohsen & Joseph Mudd & Prasun K. Datta & Nicholas J. Maness & Gabrielle Lehmicke & Nadia Golden & Linh Hellmers & Carol Coyne & Kristyn Moore Gr, 2024. "Non-human primate model of long-COVID identifies immune associates of hyperglycemia," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Al Ozonoff & Naresh Doni Jayavelu & Shanshan Liu & Esther Melamed & Carly E. Milliren & Jingjing Qi & Linda N. Geng & Grace A. McComsey & Charles B. Cairns & Lindsey R. Baden & Joanna Schaenman & Albe, 2024. "Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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