COVID-19 may cause greater loss of gray matter and tissue damage in the brain than naturally occurs in people who have not been infected with the virus, a large new study finds.
The study, published Monday in the journal Nature, is believed to be the first involving people who underwent brain scans both before they contracted Covid and months after. Neurological experts who were not involved in the research said it was valuable and unique, but they cautioned that the implications of the changes were unclear and did not necessarily suggest that people might have lasting damage or that the changes might profoundly affect thinking, memory, or other functions.
The study, involving people aged 51 to 81, found shrinkage and tissue damage primarily in brain areas related to the sense of smell; some of those areas are also involved in other brain functions, the researchers said.
“To me, this is pretty convincing evidence that something changes in the brains of this overall group of people with Covid,” said Dr. Serena Spudich, chief of neurological infections and global neurology at the Yale School of Medicine, who was not involved in the study.
But, she cautioned: “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.’”
The study involved 785 participants in UK Biobank, a repository of medical and other data from about half a million people in Britain. The participants each underwent two brain scans roughly three years apart, plus some basic cognitive testing. In between their two scans, 401 participants tested positive for the coronavirus, all infected between March 2020 and April 2021.
The other 384 participants formed a control group because they had not been infected with the coronavirus and had similar characteristics to the infected patients in areas like age, sex, medical history, and socioeconomic status.
With normal aging, people lose a tiny fraction of gray matter each year. For example, in regions related to memory, the typical annual loss is between 0.2 percent and 0.3 percent, the researchers said.
But Covid patients in the study — who underwent their second brain scan an average of four and a half months after their infection — lost more than noninfected participants, experiencing between 0.2 percent and 2 percent additional gray matter loss in different brain regions over the three years between scans. They also lost more overall brain volume and showed more tissue damage in certain areas.
“I find it surprising in the sense of how much more was lost and how generalized it is,” said Dr. Spudich, who has studied the neurological effects of Covid. She added, “I wouldn’t have expected to see quite so much percentage change.”
The effects may be particularly notable because the study involved mostly people who — like the majority of Covid patients in the general population — were mildly affected by their initial Covid infection, not becoming sick enough to need hospitalization.
The study’s lead author, Gwenaëlle Douaud, a professor in the department of clinical neurosciences at the University of Oxford, said that although the number of hospitalized patients in the study, 15, was too small to yield conclusive data, results suggested that their brain atrophy was worse than the mildly afflicted patients.
People who had Covid also showed greater decline than uninfected people on a cognitive test related to attention and efficiency in performing a complex task. But outside experts and Dr. Douaud noted that the cognitive testing was rudimentary, so the study is very limited in what it can say about whether the gray matter loss and tissue damage the Covid patients experienced affected their cognitive skills.