The COVID pandemic continues and lockdowns have come and gone, but long COVID still remains an urgent puzzle that scientists are trying to solve. Studies say it affects anywhere from 7.5 to 41 percent of adults with COVID, and the CDC lists a long list of symptoms that can come with it, from intense fatigue and difficulty breathing to brain fog, headaches, depression, and even changes in your period. The real mystery — and the key to finding an effective treatment — is what truly causes long COVID. And while many explanations are currently being studied, a new team of scientists thinks some cases may have to do with serotonin.
In short, their study, published this week in Cell, found that remaining viral particles present in some long COVID patients may trigger an immune reaction that leads to lower levels of serotonin. That, in turn, might be the cause behind some of the neurological symptoms of long COVID.
To get to those findings, the researchers analyzed the blood of long COVID patients, comparing them to people with no long COVID symptoms and patients who were in the early stages of a COVID infection. They found that infected people displayed altered levels of serotonin and other molecules involved in metabolic reactions, a common reaction known to follow viral infections, lead author Maayan Levy, PhD, assistant professor of microbiology at the Perelman School of Medicine, told the New York Times.
In people with long COVID, though, serotonin didn’t bounce back to pre-infection levels. It was the only “significant molecule” not to do so, Dr. Levy said.
The researchers also found viral particles remaining in stool samples from some of the long COVID patients. The two factors — low serotonin levels and viral particles remaining in the gut — are opposite ends of the same pathway, the scientists believe. Essentially, the immune system mounts a response to those viral remnants. Part of that response is to produce proteins that fight infection, called interferons, which cause inflammation and reduce the body’s ability to absorb tryptophan, an amino acid that helps produce serotonin in the gut. Blood clots, which can form after a COVID infection, may also disrupt the body’s ability to circulate what serotonin it does have.
That leads to lower serotonin levels, which affects the all-important vagus nerve system, the system that transmits signals between body and brain. Because serotonin plays a role in short-term memory, “the researchers proposed that depleted serotonin could lead to memory problems and other cognitive issues that many people with long Covid experience,” NYT reports.
The study is small, researchers said, which means further research will be needed to confirm the findings. In addition, not all long COVID patients have shown lower serotonin levels. Serotonin may only take a hit in some patients, Dr. Levy noted, such as those whose long COVID “involves multiple serious symptoms.”
Still, the link to serotonin has some major potential implications. The researchers told NYT that they plan to start a clinical trial to test Prozac as a treatment for long COVID. The selective serotonin reuptake inhibitor (SSRI) is used to treat depression, OCD, and panic disorder, among other conditions, according to Mayo Clinic.
The idea is that, “If we supplement serotonin or prevent the degradation of serotonin,” Dr. Levy told NYT, “maybe we can restore some of the vagal signals and improve memory and cognition” in long COVID patients with neurological symptoms.
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