COVID-19 and the Brain: Study Finds Inflammation and Vessel Damage, But No Infection

The neurological and psychiatric symptoms of SARS-CoV-2 infection have been well-documented, including loss of smell and taste, delirium and fatigue. A new study looking in detail at the brains of those who have died after infection has identified signs of damage but no obvious signs of viral spread.

The study, published in the New England Journal of Medicine, was authored by researchers from the NIH's National Institute of Neurological Disorders and Stroke (NINDS). The team examined the brains of 18 people who had died after experiencing COVID-19 symptoms between March and July 2020. The sample included patients of a range of ages, disease courses and risk factors.

An initial analysis used a high-powered brain imaging scanner – an 11.7-tesla magnetic resonance imaging (MRI) system – to examine the patients’ olfactory bulbs and brainstems. These areas were targeted as symptoms of COVID-19 affecting these brains regions, such as loss of smell and encephalitis, have been widely reported.

Bright spots in the brain

This initial analysis highlighted intensely bright spots in the patients’ brains, which represented areas where the brain's blood supply system – the microvasculature – had been damaged. Other signs noted included tiny bleeds into the brain and congestion of blood vessels, marked by dark spots on the scan.

Focusing in on these areas, the team conducted standard histopathological analysis, where brain sections are stained, and cells or molecules of interest are highlighted.

This showed that immune cells such as macrophages and CD8+ T cells had infiltrated into patients’ brains, congregating around the bright spots on the scan. The dark spots were relatively free of inflammatory markers.

Dr Avindra Nath , clinical director at NINDS and the senior author of the study, said in a press release , "We were completely surprised. Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases."

No sign of virus in the brain

Previous research has identified rare instances of SARS-CoV-2 viral particles in brain samples. The team used polymerase chain reaction (PCR), RNA sequencing and in situ hybridization techniques to search for any such particles in their patients' brain samples. The search turned up no evidence of viral intrusion, although the authors acknowledged that such particles may have already been naturally cleared from the brain prior to analysis, or may have existed in minute levels below the detection limits of their assays.

Summing up his team’s results, Nath said, “We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the body's inflammatory response to the virus."

Although the small sample size limits how much interpretation can be made from these results alone, the study adds to a growing body of literature around COVID-19 and the brain that points to a key role of a reactive immune system in pathology. "So far, our results suggest that the damage we saw may not have been not caused by the SARS-CoV-2 virus directly infecting the brain," said Nath. "In the future, we plan to study how COVID-19 harms the brain's blood vessels and whether that produces some of the short- and long-term symptoms we see in patients."