Low cortisol levels could be causing neurological issues associated with long COVID cases.
Researchers at the University of Colorado Boulder have made a discovery that could explain the neurological symptoms experienced by those suffering from long COVID, when cases extend well beyond the initial infection period. Many comfortable, and sometimes even debilitating symptoms can linger, including lack of taste and smell, depression, brain fog, severe fatigue, confusion, difficulty concentrating, and memory problems, to name a few. The study suggests that proteins left behind by the virus after infection can lead to a cortisol changes, specifically low cortisol levels, triggering inflammation in the nervous system, and causing the brain’s immune cells to overreact to stress. It is estimated that more than one-third of those who get COVID (35%) will go on to experience these long-term effects.
The research team injected a COVID-19 protein known as S1, a subunit of the spike protein, into the spinal fluid of rats. The spike protein is a key structure on the surface of the SARS-CoV-2 virus, which causes COVID-19. It is responsible for allowing the virus to enter human cells and, ultimately, lead to an infection. The S1 protein was chosen because it mimics the persistent antigens found in the bloodstreams of long COVID patients.
Just even days after exposure to S1, the cortisol changes were evident. The team noted a 31% drop in corticosterone, the rat equivalent of cortisol, in the hippocampus, a part of the brain essential for memory and decision-making. By day nine, corticosterone levels had decreased by 37%, indicating a prolonged impact on the brain’s stress response system.
A significant drop in cortisol can lead to emotional instability, cognitive issues, and a reduced capacity to handle daily challenges. It can also contribute to depression and anxiety, cause chronic fatigue, and impair immunity, which can, in turn, lead to inflammation and autoimmune challenges. Low cortisol levels can lead to poor blood sugar regulation, resulting in hypoglycemia (low blood sugar levels), negatively impacting cognitive clarity and overall brain health.
In a follow-up experiment, the team exposed the rats that had been injected with the S1 protein to a mild immune stressor. This stressor was designed to reenact a common challenge the body might face, such as a mild infection or mental distress. After doing so, the researchers observed notable changes in behavior, including changes to eating and drinking patterns, as well as change in heart rate, body temperature, and increased activation of immune cells in the brain (glial cells). The rats that had been exposed to the S1 protein had a much stronger reaction to the stressor compared to those that weren’t exposed.
These results suggest that COVID-19 antigens might alter the brain’s immune response, making it more reactive to future stressors. The findings demonstrate why long COVID patients have had marked difficulties, including extreme fatigue, lethargy, brain fog, sleep disruptions, and memory issues, after even minor stresses like an argument with a family member, a bad day at work, or unexpected, upsetting news.
The study’s lead author, Matthew Frank, PhD, from the University of Colorado Boulder, believes that understanding the role of cortisol changes in long COVID could lead to new opportunities for treatment. He cautioned, however, that follow-up studies involving human subjects would be crucial to better understanding the hormone’s effects. If, in fact, cortisol is to blame for symptom resurgence in long COVID patients, more specialized, targeted treatments addressing this root cause may substantially improve quality of life.
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Long COVID symptoms may stem from low cortisol and altered brain immune response
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