Earlier this year, leading researchers discussed what we knew – and didn’t know – about COVID-19 and the brain. Since then, new findings have emerged about SARS-CoV-2 and the nervous system, including the results of an autopsy study that showed the virus to be present throughout the body and brain.
How can a respiratory pathogen like SARS-CoV-2 mess up the nervous system? That’s the question the researchers asked in January, and it’s still being asked nearly a year later.
Neurological complications from COVID are diverse and can last a long time, Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke, noted at the time. “They are largely immune-mediated, with endothelial cells in the brain being a major target,” he said. MedPage today.
Research throughout the year has supported this view. In July, a autopsy study of nine COVID patients showed vascular damage with leakage of serum proteins into the brain parenchyma, accompanied by generalized activation of endothelial cells. Consistent with other studiesthe SARS-CoV-2 virus was not detected in the brain.
But in December, a autopsy report of 44 people Those who died with COVID-19 in the first year of the pandemic showed that the SARS-CoV-2 virus had spread throughout the body – including the brain – and persisted in tissues for months. .
Despite this, there was little evidence of inflammation or direct viral cytopathology outside of the airways, reported Daniel Chertow, MD, MPH, of the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases, and co-authors. of Nature.
“We did a total of 44 autopsies and in 11 of them we were able to do a detailed brain assessment,” Chertow said. MedPage today. In most of those individuals where we had the brains [samples]we found evidence of viral RNA and proteins in several regions we sampled.”
“And in one of those patients, using a modified Vero cell line that expresses human ACE2 and TMPRSS2 receptors, we were actually able to grow the virus from the brain,” he continued. “We were therefore able to show not only the presence of viral components – RNA and proteins – but also of live viruses capable of replicating.”
Several factors set this autopsy study apart from others, Chertow pointed out. The postmortem interval was short, a median of 22 hours, he said.
Additionally, at the time of the autopsy, we freshly dissected brain tissue, he added. “We collected tissue from 10 different regions of the brain, and in each of those regions, we preserved tissue in different ways that were safe for the kinds of downstream analyzes that we did.”
The results may not be generalizable, Chertow warned. “Not everyone in our cohort was vaccinated because the study was done in the first year of the pandemic, before the vaccine was available,” he said. And most people were older and had significant comorbidities. The cohort comprised mostly severe and ultimately fatal COVID cases, and the findings may not apply to younger, healthier, or vaccinated people.
Despite its limitations, the study showed that SARS-CoV-2 has the potential to spread cells and tissues throughout the body and brain, although it leaves important questions unanswered.
“This is a meticulously performed detailed study showing that SARS-CoV-2 infection is indeed systemic and involves many organ systems, including the brain,” observed Ziyad Al-Aly, MD, from Washington University in St. Louis, who was not involved in the research.
“What the study does not show is the presence of inflammation, cytopathology, or a clear mechanistic explanation for the neurological complications of SARS-CoV-2 infection,” Al-Aly said. MedPage today.
“Much more needs to be done to help us understand the mechanisms underlying the neurological damage we see so clearly in people with COVID-19, both in the acute phase and the long COVID phase of the disease. “, he added.
Also contributing to knowledge about COVID and the brain in 2022 was the case report of a 27-year-old patient operated on for epilepsy who recovered from COVID without respiratory compromise.
Extracellular vesicles isolated from his brain biopsy tissue showed the presence of a viral nucleocapsid protein, which was associated with endothelial cell activation, fibrinogen leakage and immune cell infiltration, reported by Nath and his co-authors in Neurology.
“We never found the virus,” Nath said. MedPage today. “We found the viral protein, but no RNA.”
Few researchers have found the virus, Nath noted. And when they find it, “it’s not like they find overwhelming amounts of virus in the brain,” he pointed out. “They find very small amounts of it.”
“The question is, really, how important is it?” he added. “Does this drive the pathology or is it just sitting there? That’s still to be understood.”
Disclosures
The autopsy study of Nature was funded and supported by the NIH Clinical Center, National Cancer Institute, National Institute of Dental and Craniofacial Research, and National Institute of Allergy and Infectious Diseases. Chertow and his co-authors reported no competing interests.
The case report in Neurology was supported by the National Institute of Neurological Disorders and Stroke. Nath and the co-authors had no relevant disclosures.
main source
Nature
Source reference: Stein SR, et al “SARS-CoV-2 infection and persistence in the human body and brain at autopsy” Nature 2022; DOI: 10.1038/s41586-022-05542-y.
Secondary source
Neurology
Source reference: DeMarino C, et al “Detection of SARS-CoV-2 nucleocapsid and microvascular disease in the brain: a case report” Neurology 2022; DOI: 10.1212/WNL.0000000000201682.
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