Scientists proposed a new explanation for some long-Covid cases, based on findings that serotonin levels were lower in people with the condition. According to a University of Pennsylvania study that was published in the journal Cell, the virus’s remaining vestiges in the stomach may be the cause of serotonin decrease. According to some, memory issues and certain neurological and cognitive effects of prolonged COVID-19 could be primarily explained by serotonin depletion.
This is just one of several recent research studies demonstrating unique biological alterations in the bodies of individuals with long-term COVID-19; these findings represent significant advancements for a disorder that manifests in a variety of ways and frequently goes undetected on common diagnostic devices like X-rays.
The findings may help guide the development of potential therapies, such as drugs that increase serotonin. The molecular mechanism that their research shows, according to the authors, may be able to reconcile several of the key theories regarding the origin of long-term COVID-19, including inflammation, increased blood clotting, autonomic nervous system dysfunction, and residual virus.
“The serotonin pathway may be the link between all these different theories,” stated Christoph Thaiss, the study’s principal author and an assistant professor of microbiology at the University of Pennsylvania’s Perelman School of Medicine.
“Secondly, even though not everyone has problems with the serotonin pathway, at least some people may benefit from treatments that stimulate this pathway,” he stated.
Yale University immunologist Akiko Iwasaki stated, “This study identifies lower levels of circulating serotonin as a mechanism for long-Covid.” In a study that was recently published, her group and others found that cortisol levels and other biological alterations were connected to certain instances of long- Covid. These investigations may identify distinct long-covid subtypes or distinct biological markers at various stages of the illness.
58 patients who had been afflicted with long-Covid for a period ranging from three to 22 months had their blood examined by researchers. These findings were contrasted with a blood analysis of 60 patients who were experiencing an early, acute stage of coronavirus infection and 30 individuals who had no post-Covid symptoms.
Lead author Maayan Levy, an assistant professor of microbiology at the Perelman School of Medicine, noted that changes in serotonin and other metabolite levels occurred quickly following a coronavirus infection, a phenomenon that is also common following other viral infections.
However, she added, serotonin was the only major chemical that did not return to pre-infection levels in individuals with long-Covid.
The scientists discovered that some of the long-term COVID patients’ stool samples still retained virus particles after analysis. Combining the data from patient studies with studies on mice and small-scale models of the human gut, which produces the majority of serotonin, the researchers discovered a mechanism that may be responsible for some long-term instances.
Interferons are proteins that the immune system produces to fight infection in response to viral leftovers. Tryptophan, an amino acid that aids in the production of serotonin in the gut, is less absorbed by the body as a result of inflammation brought on by interferons. The formation of blood clots following a coronavirus infection may hinder the body’s capacity to release serotonin.
According to the researchers, low serotonin interferes with the vagus nerve system, which is responsible for sending messages from the body to the brain. Short-term memory is influenced by serotonin, and the researchers hypothesized that low serotonin may cause memory loss and other cognitive impairments that many individuals with long-term COVID experience.
According to Dr. Iwasaki, “they demonstrated that a one-two-three punch to the serotonin pathway then leads to vagal nerve dysfunction and memory impairment.”
The study was small, so the findings need to be confirmed with additional research. Participants in other long-COVID studies, with patients having milder symptoms, did not always show depleted serotonin. Dr. Levy said it might indicate that depletion happened only in people with multiple serious symptoms of long COVID-19.
Scientists are hoping to find biomarkers for long Covid. Biological changes that can be measured will help diagnose the condition. Dr. Thaiss said the new study suggested the presence of viral remnants in stool, low serotonin, and high levels of interferons.
Most experts believe that there will not be a single biomarker for long-Covid, but several indicators will emerge and might vary, based on symptoms and other factors.
There is a need for effective ways to treat long-Covid, and clinical trials of several treatments are underway. Dr. Levy and Dr. Thaiss said they would be starting a clinical trial to test fluoxetine, a selective serotonin reuptake inhibitor often marketed as Prozac, and possibly also tryptophan.