In a study published in Science Translational Medicine last month, a team of researchers from prominent U.S. medical schools released their initial findings of possible mechanisms behind various cognitive symptoms of Long COVID. Speaking with Healio’s Emma Bascom, study author Justin J. Frere, an M.D./Ph.D. student at Mount Sinai’s Icahn School of Medicine, discussed how SARS-CoV-2 causes long-term neurological symptoms and what his study findings mean for future treatments.*

How SARS-CoV-2 can lead to lingering brain symptoms

Led by Frere, the team compared the short- and long-term immune responses in hamsters after infection with either SARS-CoV-2 virus or influenza A virus (IAV), and then validated the results in tissue from humans who recovered from COVID-19. Both viruses affected lung tissue similarly, but only SARS-CoV-2 caused an immune reaction in the olfactory system (responsible for smell) that continued for a month after the virus had cleared.

Frere explains that the “massive immune response” from the virus, which affects nearly every body part, enables the body to ultimately destroy the virus. Normally, once the infection clears, the immune response subsides and a person feels better. With COVID-19, however, the olfactory bulb (a small region of the brain) remains inflamed even after infection. Long-term, this inflammation can cause nervous system abnormalities that may lead to brain fog, anxiety, and depression.

Frere says there is still much to be done to confirm exactly what is happening. Because there are different ways SARS-CoV-2 can cause bodily damage, he says it’s possible, “if not likely,” there are multiple processes going on besides persistent inflammation.

What it means

The findings suggest that some of the brain-related Long COVID symptoms may be caused by SARS-CoV-2’s unique olfactory impact. Frere believes that clarifying this process will create an opportunity for treatment to relieve or prevent these Long COVID symptoms. The study also shows that because hamsters react to the virus similarly to humans, they represent a useful animal model for researching Long COVID therapies, making drug discovery quicker and easier.

Next steps

Frere says he wants to find out more about SARS-CoV-2’s stubborn olfactory inflammation in humans. He also wants to begin clinical studies in hamsters on potential drug treatments for brain-related viral impacts. They plan on testing corticosteroids and the antiviral pill Paxlovid to reduce olfactory inflammation and Long COVID neurological symptoms.

*Bascom, E. & Frere, J.J. (2022, June 21). Q&A: The science behind long COVID symptoms. Healio. https://www.healio.com/news/primary-care/20220621/qa-the-science-behind-long-covid-symptoms