As researchers dig deeper for the root cause of Long COVID, a discovery has been made by an investigative team led by the University of Washington (UW) School of Medicine. The team claims their observations of SARS-CoV-2 (coronavirus) dynamics fills a big knowledge gap in how a viral lung disease becomes what they say is a brain disorder in Long COVID.*

Long COVID, the CNS, and the blood-brain barrier

In the journal Brain, Behavior, and Immunity, the researchers say that the source of many Long COVID symptoms is likely the central nervous system (CNS), which consists of the brain and spinal cord. While cough and fever, for example, tend to clear up after acute COVID infection, CNS symptoms such as brain fog and memory loss often worsen.

One way SARS-CoV-2, a lung-based virus, can morph into a long, post-viral illness with mainly CNS symptoms is neuroinflammation. This inflammation can happen through a disordered blood-brain barrier (BBB). The BBB is a network of tightly grouped endothelial cells inside the brain’s blood vessels that prevent harmful molecules from entering brain tissue. 

In Long COVID, BBB disruption may happen in several ways:

• Cytokines released during the “cytokine storm” of COVID-19
• Spike protein (S1), the little red crown protruding from SARS-CoV-2 virus
• Intact SARS-CoV-2 virus

Once these mechanisms have crossed the BBB, earlier research has shown they can promote neuroinflammation.

BBB disruption is an early indicator of developing cognitive disorders.

What the researchers did

The researchers wanted to observe these mechanisms in living organisms. They created two non-infectious models of the SARS-CoV-2 virus, representing five COVID variants.

The models were tested with and without S1 protein, which attaches to host cells and determines where the virus goes.

What they found

Both models of the virus easily traversed the BBB of mice when S1 protein was present, causing neuroinflammation. 

• The virus was only able to cross the BBB with S1 attached, though S1 could be blocked from the brain by antibodies (another reason to get vaccinated, the authors note).

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

In addition:

• All five variants with S1 easily crossed the BBB, with Omicron crossing most readily.
• Neuroinflammation from S1 crossing the BBB was significantly greater in a mouse model of Alzheimer’s disease.

According to Banks, once in the brain, “S1 protein “may make [Alzheimer’s] worse, bring it on sooner, or it may cause its own version of cognitive impairment.” 

What it means

The researchers say the next step is to examine the long-term effects of neuroinflammation on a mouse brain infected with COVID virus. Since mice age more rapidly than humans, more advanced knowledge can be gained.

• Drugs that can potentially stop or prevent brain inflammation will also be tested.

Banks says “the other big concern” is that people with Alzheimer’s seem to be at greater risk for neuroinflammation once the virus gets into the brain. “[T]he study is really kind of advancing all the things that we had feared. But on the other hand, if it’s true that brain inflammation is the culprit…then we’re a little bit closer to figuring out what needs to be studied.”

*Dallas, J. (2023, February 24). Brain inflammation likely cause of long COVID symptoms, UW Medicine study finds. Yahoo!. https://www.yahoo.com/now/brain-inflammation-likely-cause-long-201009194.html