By Annie Vainshtein

Even mild cases of COVID-19 can cause brain shrinkage and an accelerated reduction of gray matter, a new study has found.

The study joins a growing body of evidence suggesting that even less severe cases of COVID-19 can affect the brain, though its authors and other experts said more research is needed to determine whether the impacts could be reversible or long-term — and it is unclear whether infection has significant effects on thinking, memory and other functions that affect quality of life.

The study, published Monday, looked at brain scans of people before they contracted the coronavirus and in months after. It is the first of its kind to take a longitudinal approach, examining changes over time.

The 785 individuals who underwent two brain scans about three years apart were sourced through UK Biobank, a biomedical database in Britain. Among the group, 401 contracted the coronavirus, most of them mild cases that did not require hospitalization, between March 2020 and April 2021.

The people within the study ranged in age from 51 to 81. Of that group, those who were infected with the coronavirus had accelerated levels of gray matter loss compared with those who never tested positive.

The natural aging process results in the loss of gray matter every year, on average between 0.2% and 0.3%, according to researchers. But the study found that compared with uninfected participants, those who contracted COVID-19 — even those who had mild cases — lost between 0.2% and 2% more gray matter across several brain regions, including ones that are related to sense of smell: the parahippocampal gyrus and the orbitofrontal cortex.

Researchers found that the participants also had higher levels of brain shrinkage and tissue damage. The study also found that participants who had suffered from COVID-19 exhibited a greater decline in efficiency and attention when performing a complex cognitive task — but that part of the research appeared to be limited, and it was not clear whether those issues would change or improve over time.

Even still, neurological experts in the Bay Area agreed that the study was either the first or among the first they were aware of to make such a compelling and direct link between COVID-19 and changes in the brain.

“SARS COV-2 has been surprising us since the beginning of the pandemic,” said Dr. Christopher Bartley, an immunopsychiatrist at UCSF. “(This study) seems to confirm a lot of the other studies that indicate that at the behavioral level or at the symptom level, that something has happened to the brain.”

Bartley and other experts acknowledged that despite the study’s sobering data, many questions and uncertainties remain. For one, the timing of the study meant that most of the participants were unvaccinated against COVID-19, leaving the implications for vaccinated people unclear.

Another question is whether the findings would have been different for a younger population, since older adults are already at a higher risk for complications from COVID-19, experts said.

They also cautioned that because the study examined participants at only two points in time, it was unclear whether the damage could be lasting.

Still, some expressed optimism about the potential for recovery.

“As we understand the effects of COVID-19 and other inflammatory conditions on brain structure and function, what’s really helpful is that some of these changes are potentially reversible,” said Dr. Michelle Monje, a professor of neurology at Stanford University. She noted that the symptoms of COVID “brain fog” sound very similar to those experienced after cancer therapy, particularly radiation - and therapeutic strategies are being developed to help alleviate them.

Overall, experts agreed that there is still more research to be done and cautioned against generalizing the findings to the population at large.

“I don’t think it necessarily tells us that there has been irreversible brain damage,” said Bartley. “(But) I hope these investigators continue to scan these individuals to look at whether or not there’s a plateau, or whether it reverses.”