Research: Long COVID Could Be Caused by Low Levels of a Key Hormone

Updated: Oct. 19, 2023

A University of Pennsylvania study identified three main factors that may be leading to ongoing symptoms for patients who have had COVID-19. 

While numerous theories have been proposed to explain why some individuals experience prolonged issues following a COVID-19 infection—a condition that’s become known as long COVID—none have adequately addressed the underlying cluster of syndromes that can be so concerning and, at times, debilitating for sufferers.

Not until a recent study published in the journal Cell on October 16, conducted by researchers from the University of Pennsylvania, suggests that lower levels of serotonin, often referred to as the “happiness hormone,” could be a contributing factor to some patients’ experiences with this condition.

Depletion of serotonin, a crucial hormone that regulates various bodily functions and influences happiness levels, was found to persist in long COVID patients. These reduced levels may be responsible for some of the syndrome’s symptoms, as hypothesized by the researchers—and, these findings could potentially point toward effective treatments.

The connection between low serotonin and long COVID

Long COVID refers to symptoms that persist after a COVID infection for an extended period, which were not present before. While these symptoms can vary significantly from person to person, commonalities among long COVID sufferers include inflammation, eyesight problems, brain fog, memory loss, chest pain, and breathing difficulties.

Lowered serotonin levels are typically associated with depression, but this hormone also regulates sleep and digestion, with 90% of it produced in the stomach. Lowered serotonin levels could account for the pervasive brain fog and memory issues that long COVID patients often grapple with, as noted by the study’s researchers. 

Additionally, these lower levels could be linked to other symptoms. Benjamin Abramoff, MD, MS, the director of Penn Medicine’s Post-COVID Assessment and Recovery Clinic and one of the study’s co-authors, mentioned in an interview with Stat News that serotonin levels remained low in people with heart and lung issues as well. “These effects can explain a wide spectrum of symptoms that our patients with long COVID have,” Dr. Abramoff said. “It certainly points us in the direction of the underlying root causes.”

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Implications for future long COVID treatment

The report examined human studies of individuals who experienced symptoms after a COVID infection, animal studies, and blood cultures of long COVID patients, searching for commonalities that could explain the symptoms. The researchers discovered that serotonin levels were more likely to be reduced in people who reported symptoms and were also lowered in laboratory mice that did not recover from COVID infection.

They identified three specific ways in which serotonin was affected after COVID infection:

  • inefficient absorption of serotonin synthesized from tryptophan in the diet in the gut
  • reduced platelet count in the blood resulting in lower serotonin levels
  • accelerated breakdown of serotonin

—all of which led to decreased levels of the circulating hormone. Moreover, they observed that patients with the lowest serotonin levels experienced more severe symptoms and were more likely to seek treatment.

The researchers acknowledged that viral infections, in general, could cause low serotonin levels. However, the continued issues seen in long COVID patients suggested that the inflammation caused by the COVID virus persisted beyond the normal course, leading to chronic serotonin depletion.

This research provides valuable insights into the treatment of long COVID symptoms and the prevention of such symptoms in COVID patients. The use of selective serotonin reuptake inhibitors (SSRIs), such as Prozac or Zoloft, as supplements or treatments, is a consideration put forth by the researchers.