Three years have passed since the emergence of novel coronavirus SARS-CoV-2, and scientists are still working to understand exactly how this virus interacts with the human body. One ongoing mystery is how broadly SARS-CoV-2 infects different organs, beyond the respiratory system.
Several studies, for example, have come to differing conclusions as to whether the neurological effects of COVID are due to the virus directly infecting brain tissue. Most recently, a team from the Stanford School of Medicine closely analyzed post-mortem brain tissue samples from several COVID patients and couldn't find any traces of viral RNA.
That research did, on the other hand, detect significant inflammatory biomarkers, leading to the hypothesis that the short- and long-term neurological symptoms could be due to persistent immune system activity. This hypothesis has been backed up by subsequent autopsy studies finding neuroinflammation in COVID patients.
This new research, led by National Institutes of Health scientists in association with the University of Maryland, autopsied 44 patients who died from, or with, COVID-19. The study focused on harvesting tissue soon after death from a variety of different locations in the body.
"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 ddPCR [polymerase chain reaction] and ISH [in situ hybridization], as well as isolate virus in cell culture from multiple non-respiratory tissues including the brain, which are notable differences compared to other studies," the researchers write in the new study.
The findings revealed SARS-CoV-2 RNA could be detected in 84 different locations in the body. The highest burden of viral RNA was found in airway and lung tissue, however, the virus was also detected in the brain, gut, heart, kidney, eye, adrenal gland, and lymph nodes.
The tissue tested came from patients at several different stages of infection, from the earliest stages (less than 14 days after symptom onset) up to nine months after the acute disease. The highest viral burden was unsurprisingly found in those patients at the earliest stages of an infection, but 14 of 27 patients beyond the two-week mark still showed the presence of virus in at least one non-respiratory tissue analyzed.
While the study's findings are certainly striking, what they mean is still unclear. All the patients included in the research were older, unvaccinated, autopsied during the first year of the pandemic, and suffered from many comorbidities. So it is unknown whether new variants of virus spread through vaccinated, younger people in similar ways.
Nevertheless, what this study does clearly illustrate is the potential for SARS-CoV-2 to spread through tissues across the entire body, including the brain. And the researchers are now asking whether this could play a role in which patients experience long COVID.
The next step for the research team is to gather postmortem tissue from deceased long COVID patients to understand whether the virus can be found months after an acute illness. This is part of a larger project dubbed RECOVER (Researching COVID to Enhance Recovery).
Alongside the tissue pathology work, the RECOVER project is running a clinical trial testing the efficacy of antiviral Paxlovid in treating long COVID patients. The hypothesis is that if long COVID symptoms are triggered by persistent SARS-CoV-2 infections in certain parts of the body, then trying to eliminate the virus with antivirals should improve those symptoms.
The Paxlovid long COVID trial is set to begin this year and the RECOVER project is slated to run up to four years.
The new research was published in Nature.
Source: National Institute of Allergy and Infectious Diseases
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