Therese Raphael

What Does Covid Do to the Brain and Mind?

Many of us have put Covid largely out of our minds. But one of the most intriguing and important areas of study is exactly what Covid does to the mind. The answer to that question is still far from clear. And yet it affects how we treat Covid as well as how we manage future pandemics and viruses.

In a study published this week in the journal Nature, neuroscientist Gwenaelle Douaud and colleagues examined brain scans of 785 participants from the UK biobank, which holds genetic data and brain scans of 40,000 people, the largest resource of its kind anywhere. Their findings offer a robust indication that getting Covid, even a mild case, changes the biology of the brain and its functioning.

A little more than half of the participants tested positive for Covid between two scans. Among those who had Covid, their scans showed a reduction in grey matter thickness in certain regions of the brain, greater changes in markers for tissue damage in regions connected to the primary olfactory cortex, governing our sense of smell, and a decrease in overall brain size. Some of the changes were the equivalent of up to a decade of normal aging. The researchers also observed decreased cognitive functioning between the two scans in participants who had Covid.

There have been other attempts to understand the effect of Covid on the brain. In a study published in Nature in June 2021, researchers used single-cell RNA sequencing on the brain tissue of people who died from Covid-19 and found signs of inflammation, chronic neurodegeneration and abnormal nerve-cell communication, compared with brain tissue samples from those who died of other causes. Those same variations have also been found in those with chronic brain disorders and those with gene variations associated with schizophrenia and depression.

The new study, which looks at changes over time in the same group of individuals, suggests that Covid changes the brain even among those who are not hospitalized. Since it involved a control group that was matched with the Covid-infected group for age, sex, ethnicity and other factors, it’s considered a gold-standard epidemiological study.

But, as the authors note, an observational study can’t make certain claims of causality or tell us how long any changes last. We know that the brain has wondrous plasticity and can repair itself over time. (For example, there are changes to grey matter in the menopausal brain that later reverts to normal, research has shown.) So we’re a long way from being able to say that Covid is a risk factor for dementia or other long-term cognitive decline.

Researchers are also looking into the link between Covid and mental health. Rates of depression and anxiety reportedly rose during the pandemic, no doubt in part due to isolation from lockdowns and other changes to daily life. But a study published last month highlighted a link between getting Covid and experiencing psychological problems. Using data from the US Department of Veterans Affairs, Ziyad Al-Aly and colleagues analyzed the records of nearly 154,000 veterans who had been infected with Covid and compared them with a control sample of 5.8 million uninfected veterans.

The authors found that those who had the virus had a 60% higher risk of being diagnosed, one year after infection, with one of 14 mental-health problems — from sleep disorders to neurocognitive decline to depressive issues — than those who were uninfected. There was a 24% increased risk of depression in the year following hospitalization with Covid compared with hospitalization with flu before the pandemic, suggesting the effect isn’t just a matter of any illness increasing the risk of mental-health problems; it was specifically Covid.

However, up to 76% of the cohort they studied was white, 90% were male and the average age was 63. It’s not clear how much we can generalize from that population. There is also the possibility of a nocebo effect, whereby expectation of a health problem or fear of it can lead to increased incidence. We know, for example, that patients who are told about side effects are much more likely to experience them.

Jessica Bernard, an associate professor at the Institute of Neuroscience at Texas A&M University who wasn’t connected to either of the studies above, says we have a chicken and egg problem. “We don’t yet know if any of the neural changes or differences that have been reported will reverse with time —- or with vaccination in individuals that became ill before vaccines were available. It is also possible that these brain impacts of Covid are impacting mental health in veterans.”

It’s tricky to devise policy that reflects these findings. Our current emphasis on pharmacological interventions — vaccines and drugs — assumes that Covid infection, if and when it comes, is now mild and temporary. Most people are comfortable with that. And if we are more likely to experience psychological problems from Covid because of fear and stress, then we ought to minimize the messaging and restrictions that may be triggers for those things.

But if just catching Covid increases our risk of short or long-term neurocognitive decline and other problems, then we also don’t want to be quite so blasé about the virus. Out of sight but back of mind might be the best way to protect the brain.