Long Covid: virus can alter serotonin, study suggests – 10/17/2023 – Health

A team of scientists is proposing a new explanation for some cases of long Covid, based on findings that serotonin levels were lower in people with the condition.

In their study, published this Monday in the journal Cell, researchers from the University of Pennsylvania suggest that the reduction in serotonin is triggered by remnants of the virus that persist in the intestine. The decrease in serotonin could especially explain memory problems and some neurological and cognitive symptoms of long Covid, they say.

Why this matters: New ways to diagnose and treat long Covid

This is one of several new studies documenting distinct biological changes in the bodies of people with long Covid — offering important insights for a condition that takes many forms and often goes undetected on standard diagnostic tools like X-rays.

The research could point the way to possible treatments, including drugs that increase serotonin. And the authors say the biological pathway their research describes could unite many of the leading theories about what causes long Covid: lingering remnants of the virus, inflammation, increased blood clotting and autonomic nervous system dysfunction.

“All of these different hypotheses may be connected through the serotonin pathway,” said Christoph Thaiss, lead author of the study and assistant professor of microbiology at the University of Pennsylvania Perelman School of Medicine.

“Second, even though not everyone experiences difficulties in the serotonin pathway, at least some may respond to therapies that activate this pathway,” he said.

“This is an excellent study that identifies lower levels of circulating serotonin as a mechanism for long Covid,” says Akiko Iwasaki, an immunologist at Yale University. Her team and colleagues at the Icahn School of Medicine at Mount Sinai recently published a study that identified other biological changes linked to some cases of this condition, including levels of the hormone cortisol. These studies could point to specific subtypes of long Covid or different biological indicators at different stages of the disease.

What it explains: disturbances triggered by virus fragments in the intestine

Researchers analyzed the blood of 58 patients who had been experiencing long Covid for a period of between three and 22 months since infection. These results were compared to blood analysis from 30 people without post-Covid symptoms and 60 patients who were in the initial acute phase of coronavirus infection.

Maayan Levy, one of the lead authors and assistant professor of microbiology at the Perelman School of Medicine, says that levels of serotonin and other metabolites were altered shortly after a coronavirus infection, something that also occurs immediately after other viral infections.

However, in people with long Covid, serotonin was the only significant molecule that did not recover to pre-infection levels, he says.

The team analyzed stool samples from some of the long Covid patients and found that they contained remnant viral particles. By combining findings in patients with research in mice and miniature models of the human intestine, where most serotonin is produced, the team identified a pathway that could be behind some cases of long Covid.

The idea is this: viral remnants stimulate the immune system to produce interferons, defense proteins. Interferons cause inflammation that reduces the body’s ability to absorb tryptophan, an amino acid that helps produce serotonin in the intestine. Blood clots that can form after a coronavirus infection can impair the body’s ability to circulate serotonin.

A lack of serotonin disrupts the vagus nervous system, which transmits signals between the body and brain, researchers say. Serotonin plays a role in short-term memory, and researchers have hypothesized that a lack of serotonin could lead to memory problems and other cognitive changes that many people with long Covid experience.

“They showed that hitting the serotonin pathway leads to vagus nerve dysfunction and memory impairment,” Iwasaki said.

There are caveats. The study was not extensive, so the results need to be confirmed with other research. Participants in other long Covid studies, in which some patients had milder symptoms, did not always have deficient serotonin, a result that Levy says may indicate that the loss occurred only in people whose long Covid involves multiple severe symptoms.

Next step: a clinical trial of Prozac

Scientists want to find biomarkers for long Covid — biological changes that can be measured to help diagnose the condition. Thaiss says the new study suggests three: the presence of viral remnants in feces, low serotonin and high levels of interferons.

Most experts believe that there will not be a single biomarker for the condition, but that multiple indicators will emerge and may vary based on the type of symptoms and other factors.

There is a huge demand for effective ways to treat Covid, and clinical trials of several treatments are underway. Levy and Thaiss say they will begin a clinical trial to test fluoxetine, a selective serotonin reuptake inhibitor often marketed as Prozac, and possibly tryptophan as well.

“If we supplement serotonin or stop the breakdown of serotonin, maybe we can restore some of the vagal signals and improve memory and cognition and so on,” says Levy.

This report was originally published here.