Coronavirus probably does not directly infect the brain but can still inflict significant neurological damage, new research has revealed.
The study into SARS-CoV-2, the virus that causes COVID-19, is the largest and most detailed brain autopsy report published to date in the wake of the pandemic, and suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain’s blood vessels.
“There’s been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients,” says Professor James E. Goldman, from the Columbia University Vagelos College of Physicians and Surgeons.
“At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects – and why those with mild cases may experience ‘brain fog’ for weeks and months.”
The study examined the brains of 41 patients with COVID-19 who died from the virus during their hospitalisation. The patients ranged in age from 38 to 97, about half had been intubated and all had lung damage caused by COVID-19.
To detect any virus in the neurons and glia cells of the brain, the researchers used multiple methods including RNA in situ hybridisation, which can detect viral RNA within intact cells, alongside antibodies that can detect viral proteins within cells, and RT-PCR, a sensitive technique for detecting viral RNA.
Despite their intensive search, the researchers found no evidence of the virus in the patients’ brain cells, although they did detect very low levels of viral RNA by RT-PCR, which was most likely due to virus in blood vessels or leptomeninges covering the brain.
“We’ve looked at more brains than other studies, and we’ve used more techniques to search for the virus. The bottom line is that we find no evidence of viral RNA or protein in brain cells,” Professor Goldman says.
“Though there are some papers that claim to have found virus in neurons or glia, we think that those result from contamination, and any virus in the brain is contained within the brain’s blood vessels.
The tests were conducted on more than 24 brain regions, including the olfactory bulb, which was searched because some reports have speculated that the coronavirus can travel from the nasal cavity into the brain via the olfactory nerve.
“Even there, we didn’t find any viral protein or RNA,” Professor Goldman continues, “though we found viral RNA and protein in the patients’ nasal mucosa and in the olfactory mucosa high in the nasal cavity.”
Despite the absence of virus in the brain, in every patient the researchers found significant brain pathology, which mostly fell into two categories.
“The first thing we noticed was a lot of areas with damage from a lack of oxygen,” Professor Goldman says.
“They all had severe lung disease, so it’s not surprising that there’s hypoxic damage in the brain.”
Some of these were large areas caused by strokes, but most were very small and only detectable with a microscope. Based on other features, the researchers believe these small areas of hypoxic damage were caused by blood clots, common in patients with severe COVID-19, that temporarily stopped the supply of oxygen to that area.
Professor Goldman added that more research is needed to understand the reasons why some post-COVID-19 patients continue to experience symptoms, and the team are now examining autopsies on patients who died several months after recovering from COVID-19 to learn more.
They are also examining the brains from patients who were critically ill with acute respiratory distress syndrome (ARDS) before the COVID-19 pandemic to see how much of COVID-19 brain pathology is a result of the severe lung disease.
