Can we clear COVID from the brain?

Gregory Nemec

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COVID-19 may start with a lung infection, but its effects can ripple through the body for months—as people with long COVID know well. Memory loss and difficulty concentrating have plagued many long-haulers. New research from Yale may explain why.

In a paper recently published in Cell, professor of immunobiology Akiko Iwasaki and collaborators at Stanford University show that even a mild bout with COVID-19 can inflict lasting damage on the brain. Moreover, the virus doesn’t have to infect brain cells to leave its mark; the researchers traced the brain changes to inflammation caused by the immune cells fighting the virus in the lung.

“Something is triggered in the body that results in a more permanent change, even in the absence of a virus,” Iwasaki says.

Immune cells release proteins called cytokines to communicate with other cells. One of these messenger molecules—CCL11—stood out to Iwasaki’s team because its levels remained high in mice even seven weeks after they’d had mild COVID-19. CCL11 levels were also elevated in blood from humans who had prolonged cognitive symptoms after recovering from mild COVID-19.

The researchers linked CCL11 to changes in the brains of the mice, such as reduced neuron growth and microglia (immune cells in the brain) that were abnormally active. Impaired neurogenesis was specifically found in the hippocampus, a part of the brain involved in learning and memory. There were also fewer oligodendrocytes, brain cells that make insulating material to protect neurons.

“The new changes within the brain are occurring even seven weeks post-infection—from a mild infection that only lasts for a week,” Iwasaki notes.  Michelle Monje, a Stanford neuro-oncologist and coleader of the study, compared the changes to the aftereffects of chemotherapy, which engenders similar brain changes and leads to its own variety of brain fog.

While the two conditions may not be identical, promising treatments for “chemo fog”—such as replacing microglia—have inspired Iwasaki’s next steps. She is now searching for similar therapies to reverse inflammation and keep brains in shape after COVID-19.