Prolonged COVID-19 Symptoms Associated with Inflammation – National Institutes of Health (.gov)

Quick overview

  • Prolonged inflammation after SARS-CoV-2 infection caused permanent damage to the lungs and kidneys, affected the brain, and was associated with behavioral changes in hamsters.
  • The findings suggest a mechanism for people’s prolonged COVID illness symptoms.

The effects of COVID-19 can persist long after the initial symptoms of the disease have passed. These effects, called post-acute sequelae of COVID-19 (or PASC), can include brain fog, fatigue, headache, dizziness, and shortness of breath. Prolonged COVID – when symptoms persist weeks or months after an acute infection has cleared – affects about 2.5% of COVID patients. While patients who have been hospitalized are more likely to be infected, even those with mild cases can suffer from COVID for an extended period.

A research team led by Dr. Benjamin Ten at New York University’s Grossman School of Medicine and Venetia Zaccario at the Icahn School of Medicine at Mount Sinai set out to understand the basic biology of the Long-Covid virus. The researchers, supported in part by the National Institutes of Health, studied the golden hamster, a small animal model widely used in respiratory infections. Hamsters were exposed to SARS-CoV-2 via nostrils. For comparison, another group was exposed to influenza A virus, and different samples were taken for analysis 3, 14, 31 days after infection.

Tissue samples were also taken and analyzed from human donors who had COVID-19 at the time of death or recovered from COVID-19 but died of other causes. Results appeared on June 7, 2022 in Translational Medicine Sciences.

SARS-CoV-2 infection and influenza A were largely eliminated within two weeks, similar to the course of recovery in humans. After infection with SARS-CoV-2, the animals showed more widespread lung damage and slower recovery than those exposed to influenza A.

When scientists took samples from different parts of hamsters’ brains to analyze genetic activity, they found that SARS-CoV-2 has unique effects on a hamster’s olfactory system – the parts of the nose and brain responsible for smell. The olfactory epithelium, the lining inside the nose, showed signs of widespread inflammation long after the virus was detected. SARS-CoV-2 also caused high levels of inflammation in the olfactory bulb, a part of the brain involved in smell processing as well as emotion and learning. Inflammation in these areas persists long after the infection has cleared.

Interestingly, chronic inflammation in the olfactory system is associated with behavioral changes in hamsters that are thought to reflect mood disorders such as depression and anxiety. Although olfactory bulb tissue is difficult to obtain from people who have recovered from COVID-19 and died of other causes, the few samples studied were similar to those from hamsters. This suggests that the inflammation seen in hamsters may explain the mechanism responsible for the symptoms of COVID-19 in humans. More research is needed to fully understand the relationship between encephalitis and brain activity and behavioral changes.

“[T]His study indicates that the molecular mechanism underlying many of the prolonged symptoms of COVID-19 stems from this persistent inflammation while describing an animal model close enough to human biology to be useful in designing future treatments,” says TenOever.

—By Larissa Gerhardt Serna, Ph.D.

Financing: National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health and the National Institute on Deafness and Other Communication Disorders (NIDCD); Zaghar Family Foundation; New York Genomics Center.

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