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

Abstract

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction 1 – 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 brain 3 , 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.

Successful lung transplantation using an allograft from a COVID-19–recovered donor: a potential role for subgenomic RNA to guide organ utilization

“…This appears driven partly by concerns about the persistence of SARS-CoV-2 viral RNA in the lung and extrapulmonary tissue, which can be detected for weeks to months after the initial diagnosis. 13 , 15 , 19 However, the detection of genomic RNA cannot differentiate replicating viruses from nonreplicating viruses, resulting in discard of organs that may not pose a risk of viral transmission. An assay capable of detecting active viral replication with high sensitivity could prove useful in further stratifying the risk of SARS-CoV-2 transmission from donors with a recent COVID-19 infection.…”

“…SARS-CoV-2 proteins and RNA have, however, been identified in multiple organs, and data suggest that viral RNA can persist in tissues for prolonged periods of time following an infection. 14 , 15 In a scenario in which a donor with a recently resolved COVID-19 infection has an LRT sample positive for SARS-CoV-2 by genomic RNA testing, sgRNA testing of an LRT sample and of a bronchial tissue via transbronchial biopsy could be performed to assess replication-competent viruses and guide organ utilization decisions ( Fig. 3 ).…”

“…Although lung allografts from SARS-CoV-2–positive donors with an active infection should be avoided, the safety of pulmonary organs from donors who have recovered from COVID-19 is not well described. Because SARS-CoV-2 RNA can be shed in the respiratory tract for weeks despite symptomatic improvement, 13 , 14 , 15 it is difficult to determine the optimal time to recover lungs from donors with a recent COVID-19 infection. This is a critical question because the exclusion of these donors could restrict an already limited resource, and the COVID-19–recovered status is increasingly prevalent.…”

COVID-19 and Prostate Cancer, Can Two Negatives Equal a Positive?

“…An outbreak of SARS-CoV-2 began in December 2019 and has infected hundreds of millions of people worldwide so far [5]. Meanwhile, this lethal virus may trigger a strong immune response in the host [6]. Thus, it would be very interesting to investigate if SARS-CoV-2 infection could enhance the host's antitumor immunity.…”

Increased neurovirulence of omicron BA.5 and XBB variants over BA.1 in K18-hACE2 mice and human brain organoids

“…The mechanism(s) whereby brain pathology/immunopathology and/or neuropathology might manifest in COVID-19 patients remains debatable, with the systemic cytokine storm and/or direct brain infection likely involved 22,[27][28][29][30][31][32] . A number of studies have now shown brain infection in COVID-19 patients [33][34][35][36][37] , with viral RNA or protein detected in the brains of 20-38% of patients that died of COVID-19 38,39 . A number of groups have also reported detection of viral RNA in cerebrospinal fluid of COVID-19 patients [40][41][42][43][44] , including patients infected with omicron virus 45 .…”