Scientists offer new explanation for long Covid | ET REALITY


This is one of several new studies documenting distinct biological changes in the bodies of people with long Covid, offering important discoveries for a condition that takes many forms and is often not recorded by standard diagnostic tools such as X-rays.

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

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

“Second, although not everyone experiences difficulties in the serotonin pathway, at least a subset 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,” said Akiko Iwasaki, an immunologist at Yale University. Her team and colleagues at the Icahn School of Medicine at Mount Sinai recently published A study which identified other biological changes linked to some cases of long Covid, including levels of the hormone cortisol. These studies could point to specific subtypes of long Covid or different biological indicators at different points in the condition.

The researchers analyzed the blood of 58 patients who had experienced long Covid for between three and 22 months since their infection. Those results were compared with blood tests from 30 people without post-Covid symptoms and 60 patients who were in the early, acute stage of coronavirus infection.

Maayan Levy, senior author and assistant professor of microbiology at the Perelman School of Medicine, said levels of serotonin and other metabolites were altered immediately after a coronavirus infection, something that also occurs immediately after other viral infections.

But in people with long Covid, serotonin was the only major molecule that did not recover to pre-infection levels, he said.

The team analyzed stool samples from some of the long Covid patients and found they contained remaining 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 underlie some cases of long Covid.

Here’s the idea: Viral debris causes the immune system to produce infection-fighting proteins called interferons. 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 affect the body’s ability to circulate serotonin.

Depleted serotonin disrupts the vagus nervous system, which transmits signals between the body and the brain, the researchers said. Serotonin plays a role in short-term memory, and researchers proposed that depleted serotonin could lead to memory problems and other cognitive problems experienced by many people with long Covid.

“They showed that a one, two or three hit to the serotonin pathway leads to vagus nerve dysfunction and memory impairment,” Dr. Iwasaki said.

There are warnings. The study was not extensive, so the findings need to be confirmed by other research. Participants in some other long Covid studies, in which some patients had milder symptoms, did not always show serotonin depletion, a result that Dr. Levy said could indicate that depletion occurred only in people whose Long Covid involves multiple serious symptoms.

Scientists want to find biomarkers for long Covid – biological changes that can be measured to help diagnose the condition. Dr. Thaiss said the new study suggested three: the presence of viral debris in stool, low levels of serotonin and high levels of interferons.

Most experts believe that there will not be a single biomarker for the condition, but rather that several indicators will emerge that can vary depending on the type of symptoms and other factors.

There is a huge need to find effective ways to treat long Covid and clinical trials of several treatments are underway. Dr. Levy and Dr. Thaiss said they would begin a clinical trial to test fluoxetine, a selective serotonin reuptake inhibitor often marketed as Prozac, and possibly also as tryptophan.

“If we supplement serotonin or prevent its degradation, maybe we can restore some of the vagal signals and improve memory and cognition, etc.,” Dr. Levy said.

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