New Scientist article - long covid and 'brain fog'2 Feb 2022 18:28
The latest insights suggest that the virus seldom infects brain cells directly, but instead causes harm through blood clots or by spurring a destructive immune response. Encouragingly, many of the effects caused by harmful immune changes are likely to be reversible.
Some neuroscientists think C19 causes symptoms by directly attacking cells in the brain - the effects may largely be down to two other important factors. One is the impact of C19 on blood vessels. Multiple studies have found abnormal clotting, which can cause stroke, in people with severe cases of C19. Autopsies have also revealed damage to blood vessels in the brain after C19 – vessel walls have become thinner, and they appear to leak proteins that might trigger an immune response.
This altered immune response has come to the fore as potentially the most significant culprit. In autopsy studies of people who had C19, researchers seldom see virus in samples of cerebrospinal fluid (CSF), the liquid that bathes the brain and spinal cord. Other studies of CSF from people with C19 have found changes in immune cells, including a higher production of chemicals that can be toxic to brain cells.
Researchers looked to parallels between the brain fog symptoms of long covid and “chemo brain”, the thinking and memory problems that can follow chemotherapy.
Those symptoms seem to be caused by the body’s immune response to the chemotherapy. The microglia, immune cells of the central nervous system, enter a more inflammatory state and change how other brain cells behave: less protective myelin is laid down on neurons, fewer neurons are generated and other brain cells are destroyed.
To find out whether something similar is happening in people with long covid, researchers studied mice that can be infected with the coronavirus, but only in their airways as they lack the receptor for direct infection in the brain.
The reseachers found chemicals in the animals’ blood and CSF that indicate they are experiencing something very similar to mouse models of chemo brain. Their brains also showed the same change in microglia cells, and a reduction in the generation of new brain cells.
Researchers also looked at brain tissue from nine people who had died from or with C19. In all nine people, the changes in microglia in the white matter were similar to what they saw in the mouse brains (bioRxiv, doi.org/gn4fcp).
In samples from the mice, the group also found the immune substance CCL11, which has been linked to problems with cognition. In another experiment, researchers looked at CCL11 levels in blood samples from people with long covid and found they were higher in those with cognitive symptoms than in those without.
Together, these findings strengthen the idea that immune responses are behind some of the effects of C19 on the brain. While severe impacts like stroke can cause lasting damage, a researcher noted “nothing that we showed in this paper should be irreversible”.
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