University of Colorado Boulder scientists have discovered that proteins left by COVID-19 can significantly lower cortisol levels in the brain, leading to heightened immune responses to new stressors.
This research, focusing on the neurological symptoms of Long COVID, utilized rats to demonstrate how SARS-CoV-2 antigens persist in the body and alter brain function. This persistent effect could explain the severe and varied symptoms of Long COVID, suggesting potential directions for further research and symptom management strategies.
Understanding COVID-19’s Long-term Impact on the Brain
Proteins left behind by COVID-19 long after initial infection can cause cortisol levels in the brain to plummet, inflame the nervous system, and prime its immune cells to hyper-react when another stressor arises, according to new animal research by University of Colorado Boulder scientists.
The study, published in the journal Brain Behavior and Immunity, sheds new light on what might underly the neurological symptoms of Long COVID, an intractable syndrome which impacts as many as 35% of those infected with the virus.
The findings come as COVID makes a striking summer comeback, with cases rising in 84 countries and numerous high-profile athletes at the Paris Olympics testing positive.
Cortisol’s Role in Long COVID Symptoms
“Our study suggests that low cortisol could be playing a key role in driving many of these physiological changes that people are experiencing with Long COVID,” said lead author Matthew Frank, PhD, a senior research associate with the Department of Psychology and Neuroscience at CU Boulder.
Previous research has shown that SARS-CoV-2 antigens, immune-stimulating proteins shed by the virus that causes COVID-19, linger in the bloodstream of Long COVID patients as much as a year after infection. They’ve also been detected in the brains of COVID patients who have died.
To explore just how such antigens impact the brain and nervous system, the research team injected an antigen called S1 (a subunit of the “spike” protein) into the spinal fluid of rats and compared them to a control group.
Cortisol Reduction and Its Consequences
After 7 days, in rats exposed to S1, levels of the cortisol-like hormone corticosterone plummeted by 31% in the hippocampus, the region of the brain associated with memory, decision making, and learning. After 9 days, levels were down 37%.
“Nine days is a long time in the life span of a rat,” said Frank, noting that rats live on average for two to three years.
He notes that cortisol is a critical anti-inflammatory, helps convert fuel into energy and is important for regulating blood pressure and the sleep-wake cycle and keeping the immune response to infection in check. One recent study showed that people with Long COVID tend to have low cortisol levels. So do people with chronic fatigue syndrome, research shows.
“Cortisol has so many beneficial properties that if it is reduced it can have a host of negative consequences,” said Frank.
Immune Response to Stressors in Exposed Rats
In another experiment, the researchers exposed different groups of rats to an immune stressor (a weakened bacteria) and observed their heart rate, temperature, and behavior as well as the activity of immune cells in the brain called glial cells.
They found that the group of rats that had previously been exposed to the COVID protein S1 responded far more strongly to the stressor, with more pronounced changes in eating, drinking, behavior, core body temperature, and heart rate, more neuroinflammation and stronger activation of glial cells.
Implications for Long COVID Treatments
“We show for the first time that exposure to antigens left behind by this virus can actually change the immune response in the brain so that it overreacts to subsequent stressors or infection,” said Frank.
He stresses that the study was in animals and that more research is necessary to determine whether and how low cortisol might lead to Long COVID symptoms in people.
But he theorizes that the process might go something like this: COVID antigens lower cortisol, which serves to keep inflammatory responses to stressors in check in the brain. Once a stressor arises – whether it be a bad day at work, a mild infection, or a hard workout – the brain’s inflammatory response is unleashed without those limits and serious symptoms come screaming back.
Those might include, fatigue, depression, brain fog, insomnia, and memory problems. Frank said he is doubtful that cortisol treatments alone could be an effective treatment for Long COVID, as they would not get at the root cause and come with a host of side effects. Instead, the findings suggest that identifying and minimizing different stressors might help manage symptoms.
Searching for Solutions
Rooting out the source of antigens –including tissue reservoirs where bits of virus continue to hide out – might also be an approach worth exploring, he suggests.
The study was funded by the nonprofit PolyBio Research Foundation. More research is underway.
“There are many individuals out there suffering from this debilitating syndrome. This research gets us closer to understanding what, neurobiologically, is going on and how cortisol may be playing a role,” said Frank.
Reference: “SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids” by Matthew G. Frank, Jayson B. Ball, Shelby Hopkins, Tel Kelley, Angelina J. Kuzma, Robert S. Thompson, Monika Fleshner and Steven F. Maier, 21 July 2024, Brain, Behavior, and Immunity.
DOI: 10.1016/j.bbi.2024.07.034
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6 Comments
This article has just confirmed my suspicions from stressors I experienced earlier this Spring! After having Covid 3x, ( once every year since 2020) I had a severe reoccurrence of a low back injury, I could barely walk without excruciating pain. This did not let up for a week! Finally after much treatment and pain pills, it began to get better. Ended up taking 6 weeks off work and physical therapy before I could go back.
THEN, a very strange illness started with painful red lumps randomly protruding from both of my legs!. Doctor dx my with Erythema Nervosa. Which is considered an Autoimmune response. We just couldn’t figure out the cause. The Stressor was my back injury! The lumps tooks weeks to calm down. It also caused 2+ pedal edema in both feet and have left dark scars on my legs.
I mentioned to my doctor, “Could it be from Long COVID?” He wasn’t sure…..BAM! This article just convinced me, it was!! Crazy? Huh?
Thank you! I guess I feel some mental relief 😮💨
With no age frame to factor-in, Judy, as a now eighty year old lay male who’s been battling externally imposed chronic illness since early 1981, exacerbated with a partially disabling low back injury in 1995, who neither got vaccinated nor acquired Covid-19, your having it three times strongly suggests a weakened immune system to me. Some additional immunity lowering stressors your doctor may not yet be aware of are nearly subclinical non-IgE-mediated food allergies and officially (FDA in the US) approved food poisoning (e.g., soy, added MSG and the cooking oil preservative TBHQ, minimally). If you are a younger woman, estrogen may be protecting you from having a high serum level of potentially harmful uric acid (gout) and free radicals but, if you are postmenopausal and not on HRT, a high serum level of uric acid accompanied with higher levels of free radicals may be negatively impacting your health to cause things like sluggish metabolism, fatigue, muscle weakness, excess weight, hair loss and vision problems, minimally. More free details on the “About” page of my personal video channel: (https://odysee.com/@charlesgshaver:d?view=about). Best wishes.
Or maybe mpox? Read those symptoms
Cause usually precedes effect. Click on the link to more details in my comments above to learn of real causes that preceded even the so-called “Covid-19 pandemic,” by decades.
I thought cortisol was a stress hormone that causes belly fat and even hallucinations at very high levels (Chronic Stress Disorder) and several articles I read linked insanely high cortisol levels with Covid and lockdowns (road rage is through the roof, for example). I’ve been taking Ashwagandha and Valerian as such to try and LOWER my cortisol levels as I’ve been having unexplained tactile hallucination sensations for months now after getting Covid for the 5th time last January (despite 3 vaccinations). High cortisol also equals weight gain!
So now this article comes 9ng and says Covid causes LOW Cortisol levels (in the brain; is that different from elsewhere?
The article makes zero distinction or mention of such things. It’s reminding me of the absolutely ridiculous coffee is good/bad for you ping pong game. Which is it? This is bar none the first time I’ve EVER seen a health article say Cortisol is good for you.
“To explore just how such antigens impact the brain and nervous system, the research team injected an antigen called S1 (a subunit of the “spike” protein) into the spinal fluid of rats and compared them to a control group.” That’s not a good model for a brain infected by a virus. Injecting the spinal column with the antigen, along with the other ingredients in the injection, causes trauma and pain for the animal, which will affect the rats’ brain hormone levels, including cortisol.
“He stresses that the study was in animals and that more research is necessary to determine whether and how low cortisol might lead to Long COVID symptoms in people.” So why do these cruel studies on rats, injecting them in the central nervous system with a needle, when the results are of no known application to humans, who are not injected into the brain but get COVID from other exposure?
Realize that COVID virus enters the brain through the blood-brain barrier, not through a trauma-causing needle. These rats were traumatized and abused, so it would be no surprise that their responses to further abuses, like giving them an infection as done in this study, would elicit a more extreme response than the response from a non-traumatized rat. “They found that the group of rats that had previously been exposed to the COVID protein S1 responded far more strongly to the stressor, with more pronounced changes in eating, drinking, behavior, core body temperature, and heart rate, more neuroinflammation and stronger activation of glial cells.” Sounds like a stress response to repeated abuse.
The bottom line of this cruel experiment: “Frank said he is doubtful that cortisol treatments alone could be an effective treatment for Long COVID, as they would not get at the root cause and come with a host of side effects. Instead, the findings suggest that identifying and minimizing different stressors might help manage symptoms.” Minimize stressors to manage symptoms. Wow, we needed to study that on animals.