Scientists at the University of Colorado Boulder COVID-19 It can significantly reduce cortisol levels in the brain and boost your immune response to new stressors.
The study focused on the neurological symptoms of long COVID and used rats SARS-CoV-2 Antigens persist in the body and alter brain function. This persistent effect may explain the severe and varied symptoms of Long COVID and suggests directions for further research and symptom management strategies.
Understanding the long-term effects of COVID-19 on the brain
A protein left behind by COVID-19 long after the initial infection can plummet cortisol levels in the brain, inflame the nervous system and prime immune cells to overreact when another stressor arises, according to a new animal study from scientists at the University of Colorado Boulder.
The study, published in the journal Brain, Behavior and Immunity, sheds new light on what underlies the neurological symptoms of Long COVID, an incurable syndrome that affects 35% of people infected with the new coronavirus. virus.
The findings come as the coronavirus has seen a dramatic resurgence over the summer, with cases rising in 84 countries and a number of high-profile athletes from the Paris Olympics testing positive.
The role of cortisol in long COVID symptoms
“Our study suggests that reduced cortisol may play an important role in driving many of the physiological changes people are experiencing with Long COVID,” said lead author Matthew Frank, PhD, a senior research fellow in the Department of Psychology and Neuroscience at the University of Colorado Boulder.
Previous studies have found that SARS-CoV-2 antigens, immune-stimulating proteins released by the virus that causes COVID-19, persist in the bloodstream of long COVID patients for as long as a year after infection, and have also been detected in the brains of deceased COVID patients.
To explore how such antigens affect the brain and nervous system, the team injected an antigen called S1 (a subunit of the “spike” protein) into the spinal fluid of rats and compared it with a control group.
Decreasing cortisol and its consequences
After seven days, rats exposed to S1 had levels of the cortisol-like hormone corticosterone plummeting by 31% in the hippocampus, a region of the brain associated with memory, decision-making, and learning. After nine days, levels had fallen by 37%.
“Nine days is a long time in a mouse’s lifespan,” Frank said, noting that the average mouse lifespan is two to three years.
Cortisol is an important anti-inflammatory, helps convert fuel into energy, regulates blood pressure and sleep-wake cycles, and is important in suppressing the immune response to infection, he notes. One recent study showed that people with long COVID tend to have lower cortisol levels. Research has shown the same is true for people with chronic fatigue syndrome.
“Cortisol has many beneficial properties, so a reduction in it can have a variety of negative effects,” Frank said.
Immune response in stressed rats
In another experiment, the researchers exposed different groups of rats to an immune stressor (a weakened bacteria) and then monitored the rats’ heart rate, body temperature, behavior, and activity of immune cells called glia in the brain.
The researchers found that the group of rats previously exposed to the COVID protein S1 responded much stronger to the stressor, with more pronounced changes in eating, drinking, behavior, core temperature and heart rate, as well as more neuroinflammation and greater glial cell activation.
Implications for long-term COVID treatment
“We show for the first time that exposure to antigens left behind by this virus actually alters the immune response in the brain, potentially causing an overreaction to subsequent stress or infection,” Frank said.
He stressed that the study was in animals and that further research is needed to determine whether and how low cortisol causes long COVID symptoms in humans.
But he theorizes that the process might work like this: COVID antigens lower cortisol, a hormone in the brain that helps suppress the inflammatory response to stressors. When a stressor occurs — a bad day at work, a minor infection, or strenuous exercise — the brain’s inflammatory response is unleashed unchecked, and severe symptoms return.
This could include fatigue, depression, brain fog, insomnia, and memory problems. Frank said he doubts cortisol treatment alone would be effective in treating long-covid, as it doesn’t address the underlying cause and comes with many side effects. Instead, the study suggests that identifying and minimizing various stressors may help manage symptoms.
Searching for a solution
Eradicating sources of antigens, including tissue reservoirs where viral fragments continue to hide, may also be an approach worth considering, he suggests.
The research was funded by the nonprofit PolyBio Research Foundation, and further studies are ongoing.
“There are a lot of people who suffer from this debilitating syndrome, and this study brings us one step closer to understanding what’s going on neurobiologically and what role cortisol plays,” Frank said.
Reference: “SARS-CoV-2 S1 Subunit Produces Long-Term Priming of Neuroinflammatory, Physiological, and Behavioral Responses to Distant Immune Challenge: Role of Corticosteroids,” Matthew G. Frank, Jayson B. Ball, Shelby Hopkins, Tel Kelley, Angelina J. Kuzma, Robert S. Thompson, Monika Fleshner, Steven F. Maier, July 21, 2024, Brain, Behavior, and Immunity.
DOI: 10.1016/j.bbi.2024.07.034
