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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 758-763 |
| Number of pages | 6 |
| Journal | Nature |
| Volume | 612 |
| Issue number | 7941 |
| DOIs | |
| State | Published - Dec 22 2022 |
Funding
This study was financed and supported by the Intramural Research Program of the National Institutes of Health, Clinical Center, the Center for Cancer Research within the National Cancer Institute, the National Institute of Dental and Craniofacial Research and the National Institute of Allergy and Infectious Diseases. This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research and the Colgate-Palmolive Company. The following reagent was obtained through BEI Resources, National Institute of Allergy and Infectious Diseases, NIH: Cercopithecus aethiops kidney epithelial cells expressing transmembrane protease, serine 2 and human angiotensin-converting Enzyme 2 (Vero E6-TMPRSS2-T2A-ACE2), NR-54970. We thank C. Martens, S. Anzick and K. Barbian for whole-genome sequencing and related analysis. This study was financed and supported by the Intramural Research Program of the National Institutes of Health, Clinical Center, the Center for Cancer Research within the National Cancer Institute, the National Institute of Dental and Craniofacial Research and the National Institute of Allergy and Infectious Diseases. This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research and the Colgate-Palmolive Company. The following reagent was obtained through BEI Resources, National Institute of Allergy and Infectious Diseases, NIH: Cercopithecus aethiops kidney epithelial cells expressing transmembrane protease, serine 2 and human angiotensin-converting Enzyme 2 (Vero E6-TMPRSS2-T2A-ACE2), NR-54970. We thank C. Martens, S. Anzick and K. Barbian for whole-genome sequencing and related analysis.
ASJC Scopus subject areas
- General
