Long COVID, then anxiety, depression, brain changes
Even mild cases of COVID infection can lead to long COVID and brain changes in those who suffer anxiety or depression after the infection, according to Clarissa Yasuda, MD, PhD, assistant professor of neurology at the University of Campinas in Sao Paulo. She has researched long COVID’s effects on the brain, even as she is coping with being a long COVID patient.
In one of her studies, presented at the 2023 annual meeting of the American Academy of Neurology, she found brain changes in people with anxiety, depression, and COVID but not in those infected who did not have either mental health issue. She evaluated 254 people, median age 41, after about 82 days from their positive PCR test for COVID. Everyone completed a standard questionnaire for depression (the Beck Depression Inventory) and another for anxiety (the Beck Anxiety Inventory). She further divided them into two groups – the 102 with symptoms and the 152 who had no symptoms of either depression or anxiety.
Brain scans showed those with COVID who also had anxiety and depression had shrinkage in the limbic area of the brain (which helps process emotion and memory), while those infected who didn’t have anxiety or depression did not. The researchers then scanned the brains of 148 healthy people without COVID and found no shrinkage.
The atrophy, Dr. Yasuda said, “is not something you can see with your eyes. It was only detected with computer analysis. Visualization on an MRI is normal.”
The number of people in this study with mental health issues was surprisingly high, Dr. Yasuda said. “It was intriguing for us that we noticed many individuals have both symptoms, anxiety and depression. We were not expecting it at that proportion.”
The researchers found a pattern of change not only in brain structure but in brain communication. They found those changes by using specialized software to analyze brain networks in some of the participants. Those with anxiety and depression had widespread functional changes in each of 12 networks tested. The participants without mental health symptoms showed changes in just five networks. These changes are enough to lead to problems with thinking skills and memory, Dr. Yasuda said.
Explaining the links
Several ideas have been proposed to explain the link between psychological distress and long COVID risk, Dr. Wang said. “The first and most mainstream mechanism for long COVID is chronic inflammation and immune dysregulation. Several mental health conditions, such as anxiety and depression, are associated with inflammation and dysfunction and that might be the link between depression, anxiety, and long COVID.”
Another less mainstream hypothesis, she said, is that “those with long COVID have more autoantibodies and they are more likely to have blood clotting issues. These have also been found in people with anxiety, depression, or other psychological distress.”
Other researchers are looking more broadly at how COVID infections affect the brain. When German researchers evaluated the brain and other body parts of 20 patients who died from non-COVID causes but had documented COVID infections, they found that 12 had accumulations of the SARS-CoV-2 spike protein in the brain tissue as well as the skull and meninges, the membranes that line the skull and spinal cord. Healthy controls did not.
The findings suggest the persistence of the spike protein may contribute to the long-term neurologic symptoms of long COVID and may also lead to understanding of the molecular mechanisms as well as therapies for long COVID, the researchers said in their preprint report, which has not yet been peer reviewed.
In another recent study, researchers from Germany performed neuroimaging and neuropsychological assessments of 223 people who were not vaccinated and recovered from mild to moderate COVID infections, comparing them with 223 matched healthy controls who had the same testing. In those infected, they found alterations in the cerebral white matter but no worse cognitive function in the first year after recovering. They conclude that the infection triggers a prolonged neuroinflammatory response.
Can the brain changes reverse? “We don’t have an answer right now, but we are working on that,” Dr. Yasuda said. For now, she speculates about the return of brain volume: “I think for most it will. But I think we need to treat the symptoms. We can’t disregard the symptoms of long COVID. People are suffering a lot, and this suffering is causing some brain damage.”