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

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. Platt, Peter D. Burbelo, Martha Quezado, Stefania Pittaluga, Madeleine Purcell, Vincent J. Munster, Frida Belinky, Marcos J. Ramos-Benitez, Eli A. Boritz, Izabella A. Lach, Daniel L. Herr, Joseph Rabin, Kapil K. Saharia, Ronson J. Madathil, Ali Tabatabai, Shahabuddin Soherwardi, Michael T. McCurdy, Karin E. Peterson, Jeffrey I. Cohen, Emmie Wit, Kevin M. Vannella, Stephen M. Hewitt, David E. Kleiner and Daniel S. Chertow ()
Additional contact information
Sydney R. Stein: Clinical Center, 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
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
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
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
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
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
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
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

Nature, 2022, vol. 612, issue 7941, 758-763

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-05542-y

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