Reduced Serotonin Levels Could Cause Long Covid Symptoms, Study Finds

Researchers identify a mechanism through which inflammation related to the virus leads to lower levels of the neurotransmitter

long covid
The Centers for Disease Control and Prevention found that 7.5 percent of all adults in the U.S. had experienced long Covid. Catherine McQueen/Getty Images

For the past couple of years, scientists have been trying to determine what causes some people with Covid-19 to experience extended bouts of illness, called long Covid.

A paper published Monday in the journal Cell proposes that long Covid’s symptoms could in some cases be due to reduced levels of the neurotransmitter serotonin. Lower serotonin levels could cause problems with cognition seen in some long Covid patients.

“These are very important findings that help explain why serotonin levels remain low in certain long Covid patients following SARS-CoV-2 infection,” Liam O’Mahony, an immunologist at University College Cork in Ireland who did not contribute to the research, tells National Geographic’s Sanjay Mishra.

“These effects can explain a wide spectrum of symptoms that our patients with long Covid have. It certainly points us in a direction of the underlying root causes,” Benjamin Abramoff, a co-author of the study and physician at the University of Pennsylvania, says to Stat News Elizabeth Cooney.

The Centers for Disease Control and Prevention (CDC) found last year that close to one in five Covid-19 patients in the U.S. suffered from long Covid, defined as symptoms lasting three or more months, and that 7.5 percent of all adults in the U.S. had experienced long Covid. The list of symptoms connected to long Covid varies widely and includes tiredness, brain fog, difficulty breathing, depression or anxiety, diarrhea and joint pain.

Researchers have come up with several possible causes of long Covid, including viral persistence, chronic inflammation, increased risk of blood clots and dysfunction of the autonomic nervous system. The study authors write that their paper links these hypotheses together.

In the paper, the team analyzed the blood of people with long Covid, people without post-Covid symptoms and people who had recently been infected, writes the New York Times Pam Belluck. They found that both people with acute cases and long Covid had reduced levels of circulating serotonin, which is produced in the gut. Patients’ serotonin levels also predicted whether or not they developed long-term symptoms.

The researchers then investigated what mechanism could be causing serotonin levels to drop. Inducing an inflammatory response in mice like that caused by a viral infection decreased serotonin levels.

Human patients with long Covid also had elevated levels of interferons, proteins involved in the inflammatory response to infections. And some had the virus in their stool, suggesting it was still in their gastrointestinal tracts, per Stat News. Blocking interferons in mice stopped serotonin levels from dropping.

Next, the researchers investigated whether tryptophan, an amino acid that contributes to serotonin production, could also be involved. People with Covid-19 had exhibited lower tryptophan levels. Giving mice Covid-19 or inflammation limited their guts’ ability to absorb the amino acid, writes Science’s Catherine Offord.

Together, the researchers theorize that inflammation from interferons gets in the way of tryptophan absorption, which in turn reduces serotonin levels. In mice, these reduced serotonin levels disrupted vagus nerve signaling, per National Geographic. The vagus nerve transports signals between the brain, heart and digestive system. The treated mice then performed worse on memory tests, per Science.

“They showed that one-two-three punch to the serotonin pathway then leads to vagal nerve dysfunction and memory impairment,” Akiko Iwasaki, an immunologist at Yale University who was not involved in the research, tells the New York Times.

The study suggests that restoring serotonin levels could be a possible treatment for long Covid, but any treatments would need to be tested in clinical trials.

“If we supplement serotonin or prevent the degradation of serotonin, maybe we can restore some of the vagal signals and improve memory and cognition and so on,” Maayan Levy, a co-author of the study and microbiologist at the University of Pennsylvania, tells the New York Times.

Carolyn Bramante, a pediatrician at the University of Minnesota who did not contribute to the findings, tells National Geographic that “people should only act in connection with their physician and in ways that are supported by data.”

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