A recent study involving animals has found that proteins related to COVID-19 can significantly impact the brain’s hormones and immune responses long after the initial infection.
Researchers from the University of Colorado Boulder have discovered that proteins associated with COVID-19 can lead to decreased levels of cortisol in the brain and increase inflammation in the nervous system. These changes may also cause immune cells to react more intensely to future stressors.
This study, which appears in the journal Brain Behavior and Immunity, offers new insight into the possible neurological issues tied to Long COVID, a persistent syndrome affecting about 35% of individuals who contract the virus.
The findings emerge as COVID cases are rising again in 84 countries, including positive tests among several well-known athletes at the Paris Olympics.
“Our study indicates that reduced cortisol levels might significantly influence the physical changes observed in people with Long COVID,” explains lead author Matthew Frank, PhD, a senior research associate in the Department of Psychology and Neuroscience at CU Boulder.
Prior studies indicate that SARS-CoV-2 antigens, which are immune-stimulating proteins released by the virus, can remain in the bloodstream of Long COVID patients for up to a year. These proteins have also been found in the brains of individuals who died from COVID-19.
To understand the effects of these antigens on the brain and nervous system, the research team injected a specific antigen known as S1 (a component of the virus’s “spike” protein) into the spinal fluid of rats, comparing their responses to a control group.
After 7 days, the rats exposed to S1 showed a reduction of 31% in the levels of corticosterone, a hormone similar to cortisol, within the hippocampus—a brain area crucial for memory, decision-making, and learning. By the 9-day mark, the reduction reached 37%.
“Nine days is quite a significant period in a rat’s life,” Frank noted, considering rats typically live for two to three years.
Cortisol plays an essential role in reducing inflammation, converting food into energy, regulating blood pressure, managing sleep cycles, and controlling the immune response to infections. Research has indicated that individuals with Long COVID generally exhibit low cortisol levels, a common trait among those with chronic fatigue syndrome as well.
“The beneficial effects of cortisol are numerous, and a decrease can lead to various adverse consequences,” Frank stated.
In a separate experiment, the researchers subjected different rat groups to an immune stressor (a weakened bacteria) and monitored their heart rates, temperatures, behaviors, and the activity of brain immune cells known as glial cells.
They found that the rats previously exposed to the COVID protein S1 demonstrated a significantly stronger reaction to the stressor, evidenced by marked changes in eating and drinking habits, behavior, core body temperature, heart rate, increased neuroinflammation, and heightened glial cell activation.
“This is the first time we’ve shown that exposure to virus remnants can alter the brain’s immune response, causing it to overreact when new stressors or infections occur,” added Frank.
Frank emphasizes that since this study was conducted on animals, more research is needed to understand whether and how low cortisol levels could lead to Long COVID symptoms in humans.
He speculates that the process may unfold as follows: COVID antigens reduce cortisol levels, which normally help manage inflammatory reactions to stressors in the brain. When a new stressor appears—be it a challenging workday, a minor illness, or an intense workout—the brain’s inflammatory response is unleashed without restriction, leading to a resurgence of severe symptoms.
These symptoms may include fatigue, depression, brain fog, sleep issues, and memory difficulties. Frank expressed skepticism that cortisol treatments alone could effectively address Long COVID, as they wouldn’t target the underlying cause and may introduce various side effects. Instead, the research suggests that identifying and reducing different stressors could help alleviate symptoms.
Another avenue worth exploring may be locating the sources of these antigens, including areas where remnants of the virus still exist.
This study was supported by the nonprofit PolyBio Research Foundation, and additional research is ongoing.
“There are many individuals suffering from this debilitating syndrome. This research brings us closer to understanding the neurobiological processes at play and the potential role of cortisol,” Frank concluded.
