The study involved 785 British patients, ages 51 to 81, who underwent at least two brain scans, administered on average three years apart. A total of 401 participants tested positive for infection with SARS-CoV-2 (the virus that causes COVID-19) between the two scans. Fifteen were hospitalized. “Despite the infection being mild for 96 percent of our participants, we saw a greater loss of gray matter volume [or thickness] and greater tissue damage in the infected participants, on average four and a half months after infection,” said the lead author, Gwenaëlle Douaud, PhD, an assistant professor at the Nuffield Department of Clinical Neuroscience at the University of Oxford, in a press release. On average, those infected displayed an additional 0.2 percent to 2 percent loss of gray matter or tissue damage compared with those who didn’t get COVID-19. Brain reduction and tissue damage were most prominent in areas of the brain linked to smell. Many people who have had the virus have complained of a temporary loss of smell.
COVID-19 Appears to Affect Cognition
The patients in the study took rudimentary cognitive assessments at the time of the two scans, which allowed the researchers to compare performance. While these assessments were limited in scope, making it difficult to extrapolate the results, participants with COVID-19 showed a greater decline in certain mental abilities than those not infected. Specifically, in neuropsychological exercises involving sequencing of numbers and letters, COVID-19 survivors took significantly more time to complete the tasks than those who had not been infected. The study noted that all negative outcomes were more noticeable in patients who were older. Dr. Douaud and her collaborators found no signs of memory impairment in their sample of infected participants with mainly mild symptoms. They also pointed out that their statistics represent an average effect, meaning not every infected participant experienced brain abnormalities or mental decline. Michelle Monje-Deisseroth, MD, a professor of neurology at Stanford University in California who was not involved with the research, says the study provides compelling evidence that COVID-19 can cause lasting effects on brain structure and function, even in people with relatively mild symptoms during the acute phase of the infection. “It adds to the growing evidence associating COVID-19 with persistent cognitive impairment and fits well with our increasing understanding of the neurobiological effects of COVID and COVID-induced inflammation,” says Dr. Monje-Deisseroth. Because the period of study concluded in April 2021, scientists noted that results mainly reflected effects associated with the original strain of the coronavirus and with the alpha variant. Few subjects, if any, were likely to have had the delta variant, and none would have had omicron.
Study Builds on Previous Research About COVID-19 and the Brain
The link between COVID-19 and harm to the brain is not news. As early as the summer of 2020, Johns Hopkins University was reporting that COVID-19 patients experienced a range of negative brain effects, including confusion and life-threatening strokes. For many people who get COVID-19, one of the first signs of infection is a bad headache. A study from the University of Pittsburgh published in JAMA Network Open in May 2021 found that of 3,744 hospitalized adult patients with COVID-19, four out of five had neurological symptoms. Nearly 4 out of 10 patients reported having headaches, and approximately 3 out of 10 said they lost their sense of smell or taste. Research from NYU Grossman School of Medicine published in the Journal of Neurological Sciences last year found that 91 percent of hospitalized patients, whether or not they had a neurological diagnosis when first hospitalized, had such problems six months after going home. Study authors concluded that these findings may be the hallmarks of the degenerative spread of COVID-19, either via pathways related to the sense of smell, inflammation or immune response of the nervous system, or a lack of sensory input owing to a loss of smell.
The Long-Term Impact of COVID-19 on the Brain Is Still Unclear
“A key question for future brain imaging studies is to see if this brain tissue damage resolves [improves] over the longer term,” said Douaud in her press statement. Monje-Deisseroth adds that further research is needed to understand the cellular and molecular mechanisms behind the virus’s effect on the brain. “And potential therapeutic strategies to mitigate these effects is urgently needed,” she says.
