Brain inflammation likely cause of long COVID symptoms, UW Medicine study finds

Inflammation is likely the cause of brain fog and vanishing memory during long COVID, according to a new study by the University of Washington Medicine.

Dr. William Banks, a professor with the UW Division of Gerontology & Geriatric Medicine and associate chief of staff for Research and Development at the VA Puget Sound Health Care System, had a case of long COVID, which is a version of the virus that lingers for months and raises the risk of long-term impairment.

“I couldn’t remember things and I lost my ambition to remember,” Banks said. “The two together were terrible.”

Banks, Shelly Erickson and a team of researchers with the University of Washington School of Medicine, the Veterans Affairs Puget Sound Health Care System, and Oregon Health Sciences University conducted a study on COVID.

The findings add a major piece to the puzzle of how COVID-19, a lung disease, becomes long COVID, a disease of the brain, said UW Medicine.

Using mice they observed that the S1 protein, after attaching to all SARS-CoV-2 variants, passed through the blood-brain barrier. Once there, the protein caused inflammation. This inflammation can spur problems with learning and memory and accelerate the effects of Alzheimer’s and other cognitive impairments, said Banks.

“SARS-CoV-2 causes inflammation in the brain. That’s the critical point,” said Banks. “Basically, the S1 protein, either by itself or as part of the virus, gets into the brain and you’re off to the races.”

In the study, researchers used two viruses that were noninfective and both entered the mouse brains easily. The S1 protein is the little red flower in most pictures of the coronavirus and determines where the virus goes. Researchers showed that the virus could not cross the blood-brain barrier without the S1 protein. Of the five COVID variants, Omicron passed the barrier most easily.

They also found that the S1 protein can be blocked from the brain with antibodies.

This is another reason to get vaccinated since the vaccine produces antibodies that block the S1 protein from getting into the brain, said Banks.

People with Alzheimer’s and similar diseases seem to be at particular risk when the S1 protein crosses the brain.

“It may make it worse, bring it on sooner, or it may cause its own version of cognitive impairment,” Banks said. “By analogy, that’s what diabetes does. It increases the risk of Alzheimer’s disease and it also creates its own version of cognitive impairment. This sort of ups the odds that something like this could happen with SARS-CoV-2.”

The next step for the study is examining animals to see the long-term effects of inflammation on a brain that’s been infected with COVID. Months are years for mice brains, which allows a more advanced understanding of the disease. The researchers also want to test drugs that might block or prevent certain kinds of brain inflammation.

“I think the other big concern is that we’re showing that the Alzheimer’s disease model has a lot more inflammation, so the study is really kind of advancing all the things that we had feared,” Banks said. “But on the other hand, if it’s true that brain inflammation is the culprit, which we also think is the culprit for cognitive impairment and brain injury in football injuries and everything else, then we’re a little bit closer to figuring out what needs to be studied.”

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