Covid can leave a mark on the brain, even if we haven't been infected.

BarcelonaThe stress, isolation, disruption of habits and uncertainty caused by Covid-19 five years ago may have left their mark on the brain, according to a new study published Tuesday in the journal Nature CommunicationsBritish researchers suggest that the context generated by SARS-CoV-2 "may have accelerated brain aging" in the population, even among those who were never infected. This effect is not irreversible, scientists advance.

Led by bioengineer and MRI data analyst Ali-Reza Mohammadi-Nejad, of the University of Nottingham's School of Medicine, the group examined longitudinal brain scans of nearly 1,000 healthy adults, all of them participants in UK Bio to aid science in the analysis of biomedical data. Some had scans before and after the pandemic; others, only before this health emergency swept the world.

Using advanced imaging and machine learning systems using a cohort of 15,334 healthy participants, the researchers estimated each participant's "brain age"—how much older their brain appeared to be compared to their actual age. And, according to their findings, those who lived through the pandemic showed signs of faster brain aging over time than those who were scanned earlier. Specifically, a person's brain appeared to age an average of 5.5 months more for every year lived during the pandemic.

The study was supported by the Nottingham Biomedical Research Centre and the National Institute for Health and Care Research (NIHR), among others. "What was surprising was that even people who hadn't had COVID showed significant increases in brain aging rates. This really shows how the experience of the pandemic itself can have affected our brain health," Mohammadi-Nejad said.

The changes were most noticeable in older people, men, and people from more vulnerable backgrounds. However, the researchers only observed a decline in certain cognitive abilities, such as mental flexibility and processing speed, in participants who did contract COVID-19. "This may suggest that the brain-aging effect of the pandemic, on its own (without infection), may not cause symptoms," the authors explain in a press release.

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For Masud Husain, professor of neurology and cognitive neuroscience at the University of Oxford, this is a very carefully conducted analysis, but he calls for caution when interpreting the results, as the difference in brain age was only a few months. "The time between scans was much shorter in people who were scanned before and after the pandemic, compared to those who had both scans before the pandemic. Therefore, we don't know if brain aging would have recovered if more time had elapsed," he tells SMC.

Maxime Taquet, associate professor in the Department of Psychiatry at Oxford, highlights that most people showed brain aging at the expected rate, but also that a higher proportion than usual showed surprising increases in brain age of 15 to 20 additional months per year. "The findings raise important questions about the long-term neurological impact of the pandemic, whether due to the infection itself or the broader psychological and social stress it caused," he admits.

Also speaking to SMC, Taquet says the study suggests the observed brain aging may reflect a “biopsychosocial” effect that combines the impact of infection with the psychological and social stress of the pandemic, but does not rule out the role of undetected infections. According to Taquet, an analysis by the Institute for Health Metrics and Evaluation estimated that more than 90% of the UK population could have been infected by the end of 2022, meaning many participants classified as “uninfected” may have had asymptomatic or undocumented cases.