Even mild cases of Covid-19 could lead to brain tissue damage and cognitive decline, according to a study published in Nature on Monday. But experts say larger, more specific studies are needed to confirm the findings.

Case study: Recovery clinics for Covid-19 long-haulers

Study details

For the study, researchers examined brain changes in 785 patients ages 51 to 81 who received two brain scans as part of the U.K. Biobank study. Of the participants, 401 developed Covid-19 between their two brain scans.

Researchers analyzed data from the brain scans, the second of which was generally around five months post-infection, and compared the results to 384 similar people who had not gotten sick, as well as a "handful" of people who had pneumonia and influenza, CBS News reports.

The researchers found that patients' brains, on average, saw a reduction in gray matter thickness in the orbitofrontal cortex, the area of the brain associated with decision-making, and the parahippocampal gyrus, the area associated with emotional and behavioral responses.

More extensive damage was observed in the brain tissue of the primary olfactory cortex, the area of the brain that receives information from smells, the study found. This makes sense since many people infected with Covid-19 lost their sense of smell, according to Gwenaëlle Douaud, lead author of the study and an associate professor at the Nuffield Department of Clinical Neurosciences at the University of Oxford.

The 15 study participants who required hospitalization for Covid-19 showed the most brain changes, but even those who had much milder disease showed differences, USA Today reports.

In general, the patients in the study who developed Covid-19 were found to have experienced a larger reduction in global brain size and greater cognitive decline on average than those who did not develop the disease. Those who tested positive for Covid-19 took longer to finish a cognitive test, on average, which suggests a decline in executive function.

Douaud noted that the patients in the study did experience "brain damage, but it is possible that it is reversible. But it is still relatively scary because it was in mildly infected people."

The study noted that its results were representative of averages and were not indicative of what would happen in every Covid-19 patient.

"Whether these abnormal changes are the hallmark of the spread of the pathogenic effects, or of the virus itself in the brain, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated," the researchers wrote in the study.

Reaction

Some experts said the results of the study are concerning but require more investigation to establish a cause and effect.

"To me, this is pretty convincing evidence that something changes in the brains of this overall group of people with Covid," said Serena Spudich, chief of neurological infections and global neurology at the Yale School of Medicine.

However, Spudich added, "To make a conclusion that this has some long-term clinical implications for the patients I think is a stretch. We don't want to scare the public and have them think, 'Oh, this is proof that everyone's going to have brain damage and not be able to function.'"

"None of [the study participants] got through enough cognitive testing to know if they had significant deficits in these many regions where they found these changes in volume," said Benedict Michael, an associate professor of neurological infections at the University of Liverpool. "We don't know that it actually means anything for the patient's quality of life or function."

Michael cautioned that the study's results also couldn't be extrapolated to the younger people experiencing brain fog or other cognitive problems after recovering from Covid-19. And since the study participants only had their gray matter and tissue damage measured once post-infection, "we don't know if it's just a transient change that gets better with recovery," he added.

Avindra Nath, chief of the section on infections of the nervous system at the National Institute of Neurological Disorders and Stroke, called the study "outstanding" and said it could "have major implications since it is unlikely [the brain damage] will reverse on [its] own after so many months. The critical question is whether this can result in an acceleration of the neurodegenerative process, since the researchers also noted global atrophy."

Nath recommended that researchers observe more patients with other coronaviruses or the flu "to see if these findings are distinct for Covid-19 or more generalizable."

"It's an important study, they've done good work," Michael said. "[N]ow we need to do the studies to look at cognition and psychiatric symptoms and behavioral stuff and neurological stuff and find out what does this mean for patients," he added. (Choi, The Hill, 3/7; George, MedPage Today, 3/7; Belluck, New York Times, 3/7; Tin, CBS News, 3/7; Weintraub, USA Today, 3/7)