Autopsies reveal startling new information

Analysis of tissue samples from autopsies of 44 people who died with[{” attribute=””>COVID-19 shows that SAR-CoV-2 virus spread throughout the body—including into the brain—and that it lingered for almost 8 months. The study was published on December 14 in the journal Nature.

Scientists from the National Institutes of Health (NIH) tested samples from autopsies that were performed from April 2020 to March 2021. They conducted extensive sampling of the nervous system, including the brain, in 11 of the patients.

RNA and viable virus in various organs

All of the patients died with COVID-19, and none were vaccinated. The blood plasma of 38 patients tested positive for SARS-CoV-2, 3 tested negative, and plasma was unavailable for the other 3.

Thirty percent of the patients were female, and the median 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.

Analysis showed that SARS-CoV-2, as expected, primarily infected and damaged airway and lung tissue. But the researchers also found viral RNA in 84 distinct body locations and bodily 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 substantial viral burden.”

“We demonstrated virus replication in multiple non-respiratory sites during the first two weeks following symptom onset.”

The investigators also isolated viable SARS-CoV-2 virus from diverse tissues in and outside the respiratory tract, including the brain, heart, lymph nodes, gastrointestinal tract, adrenal gland, and eye. They isolated virus from 25 of 55 specimens tested (45%).

The authors wrote, “We demonstrated virus replication in multiple non-respiratory sites during the first two weeks following symptom onset.”

They add, “Our focus on short postmortem intervals, a comprehensive standardized approach to tissue collection, dissecting the brain before fixation, preserving tissue in RNA later, and flash freezing of fresh tissue allowed us to detect and quantify SARS-CoV-2 RNA levels with high sensitivity by [polymerase chain reaction] and [in situ hybridization]as well as isolate the virus in cell culture from multiple non-respiratory tissues including the brain, which are significant differences compared to other studies.”

Possible consequences for the ‘long COVID’

Senior study author Daniel Chertow, MD, MPH, said at the NIH news that before the work, “the opinion in the field was that SARS-CoV-2 is predominantly a respiratory virus.”

Finding the presence of the virus throughout the body — and sharing those findings with colleagues a year ago — helped scientists investigate the link between widely infected body tissues and “long COVID,” or symptoms that persist for weeks and months after infection.

“We hope to replicate the data on the persistence of the virus and study the relationship with long-term COVID.”

— Study co-author Stephen Hewitt, MD, PhD

Part of the NIH-funded Paxlovid RECOVER trial, which is expected to begin in 2023, includes expanding the autopsy work highlighted in Nature study, according to co-author Stephen Hewitt, MD, who serves on the board of directors for the Project RECOVER. Autopsies in the RECOVER trial include people who were vaccinated and infected with the worrisome variants—data that were not available in yesterday’s study.

“We hope to replicate the persistence data 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 those 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 & Daniel S. Chertow, December 14 Nature.
DOI: 10.1038/s41586-022-05542-y