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

Nature. 2022 Dec;612(7941):758-763. doi: 10.1038/s41586-022-05542-y. Epub 2022 Dec 14.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autopsy*
  • Brain* / virology
  • COVID-19* / virology
  • Humans
  • Organ Specificity*
  • RNA, Viral / analysis
  • Respiratory System / pathology
  • Respiratory System / virology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / isolation & purification
  • SARS-CoV-2* / pathogenicity
  • SARS-CoV-2* / physiology
  • Time Factors
  • Virus Replication

Substances

  • RNA, Viral