An analysis of autopsied tissue samples from 44 people who died with COVID-19 revealed that the SAR-CoV-2 virus spread throughout the body, including the brain, and persisted for nearly 8 months.
An analysis of tissue samples from the autopsies of 44 people who died with COVID-19 shows that the SAR-CoV-2 virus spread throughout the body, including in the brain, and persisted for nearly 8 months. The study was published on December 14 in the journal Nature.
Scientists at the National Institutes of Health (NIH) tested samples from autopsies that were performed from April 2020 to March 2021. They performed comprehensive samples of the nervous system, including the brain, in 11 of the patients.
Viable RNA and virus in various organs
All patients died of COVID-19 and none were vaccinated. Blood plasma from 38 patients tested positive for SARS-CoV-2, 3 tested negative, and plasma was not available for the other 3.
Thirty percent of the patients were women and the mean age was 62.5 years. Twenty-seven patients (61.4%) had three or more comorbidities. The median interval from symptom onset to death was 18.5 days.
The analysis showed that SARS-CoV-2, as expected, primarily infected and damaged the airways and lung tissue. But the researchers also found viral RNA in 84 different body locations and body fluids, and in one case they isolated viral RNA 230 days after a patient’s symptoms began.
The researchers detected SARS-CoV-2 RNA and protein in the hypothalamus and cerebellum of one patient and in the spinal cord and basal ganglia of two other patients. But they found little damage to brain tissue, “despite the substantial viral load.”
“We have shown virus replication in multiple non-respiratory sites within the first two weeks after the onset of symptoms.”
The researchers also isolated viable SARS-CoV-2 virus from various tissues inside and outside the respiratory tract, including the brain, heart, lymph nodes, gastrointestinal tract, adrenal gland, and eye. They isolated the virus from 25 of the 55 specimens tested (45%).
The authors wrote: “We demonstrated virus replication at multiple non-respiratory sites within the first two weeks after symptom onset.”
They add: “Our focus on short postmortem intervals, a comprehensive standardized approach to tissue collection, dissecting the brain before fixation, preserving tissue for RNA later, and snap-freezing fresh tissue allowed us to detect and quantify SARS-CoV-2 RNA levels with high sensitivity for [polymerase chain reaction] i [in situ hybridization]as well as isolating virus in cell culture from multiple non-respiratory tissues, including the brain, which are notable differences compared to other studies.”
Possible ramifications for “long covid”
Lead study author Daniel Chertow, MD, MPH, said in an NIH press release that, before the work, “the thinking in the field was that SARS-CoV-2 was predominantly a respiratory virus.” .
Finding viral presence throughout the body, and sharing those findings with colleagues a year ago, helped scientists explore a link between widely infected body tissues and “long covid,” or symptoms that persist for weeks and months after the infection
“We hope to replicate the data on viral persistence and study the relationship with long-term COVID.”
– Study co-author Stephen Hewitt, MD, PhD
Part of an NIH-funded Paxlovid RECOVER trial expected to start in 2023 includes an extension of the autopsy work highlighted in the Nature study, according to co-author Stephen Hewitt, MD, PhD, who is part of a steering committee of the RECOVER project. Autopsies in the RECOVER trial include people who were vaccinated and infected with variants of concern, data that were not available in yesterday’s study.
“We hope to replicate the data on viral persistence and study the relationship with long-term COVID,” Hewitt said. “In less than a year we have about 85 cases and we are working to expand these efforts.”
Reference: “SARS-CoV-2 infection and persistence in the human body and brain at autopsy” by 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, Isabella A. Lach, Daniel L. Herr, Joseph Rabin, Kapil K. Saharia, Ronson J. Madathil, Ali Tabatabai, Shahabuddin Soherwardi, Michael T. McCurdy, NIH COVID-19 Autopsy Consortium, Karin E. Peterson, Jeffrey I. Cohen, Emmie de Witt, Kevin M. Vannella, Stephen M. Hewitt, David E. Kleiner, and Daniel S. Chertow