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October 17, 2023

Prozac could help treat long COVID symptoms, Penn researchers say

A new study suggests the antidepressant may restore serotonin levels depleted by traces of the coronavirus that linger in the gut

Illness COVID-19
Long COVID Prozac Karolina Grabowska/

New research on long COVID suggests remnants of the virus that survive in the gut may deplete serotonin levels, contributing to symptoms like brain fog and short-term memory problems. The antidepressant Prozac could be used to help restore mental balance.

Brain fog and impaired memory are some of the most common symptoms reported by people who suffer from long COVID, yet there are many unanswered questions about why these problems linger long after COVID-19 infections.

As new research on long COVID continues to build a better understanding of the condition, one study out of the University of Pennsylvania suggests the antidepressant Prozac could help resolve some of the cognitive issues affecting millions of Americans.

Prozac is among the most commonly prescribed antidepressant medications in the U.S. It works by increasing the availability of the neurotransmitter serotonin, which plays important roles in regulating mood, sleep, digestion, sexual desire, short-term memory and other functions. Serotonin is mostly produced in the gut and carries messages between nerve cells in the brain and the rest of the body.

The study out of Penn, published this week in the journal Cell, examines how long COVID disrupts healthy processes in the gut and reduces the body's ability to produce serotonin.

The researchers collected blood and stool samples from 58 patients who had complained of long COVID symptoms for periods ranging from three to 22 months. These samples were compared with people who had recovered from COVID-19 and people who were in the early stages of a new COVID-19 infection.

In some of the patients with long COVID, the researchers found that remnants of the coronavirus had remained in their guts for long periods after their initial infections. 

Lingering pieces of the virus can trigger an ongoing immune response that causes gut inflammation, reducing the body's ability to produce serotonin. And without healthy levels of serotonin, messages intended for the brain can become disrupted and lead to wider dysfunction in the body.

The researchers at Penn found that this issue is related to how the gut absorbs tryptophan, which is a key building block for serotonin. Tryptophan has roles in creating various metabolites — including the sleep-regulating hormone melatonin — but the study observed that serotonin production failed to return to normal levels after recovery from COVID-19.

"There has been some evidence to suggest that SSRIs (selective serotonin reuptake inhibitors) could be effective in preventing long COVID, and our research now presents an opportunity for future studies to select specific patients for a trial who exhibit depleted serotonin, and to be able to measure response to treatment," said Dr. Benjamin Abramoff, the study's coauthor and director of the Post-COVID Assessment and Recovery Clinic at the Perelman School of Medicine.

Although the researchers note that their study is small, they said they have seen promising results in animal models in restoring serotonin deficiency with SSRIs, like Prozac, and by replenishing tryptophan. Two of the study's authors said they will soon begin a clinical trial to analyze Prozac's ability to relieve symptoms in sufferers of long COVID.

An annual health survey conducted last year by the U.S. Centers for Disease Control and Prevention found that, since the start of the pandemic, about 18 million people reported long COVID symptoms. About 8.8 million currently are suffering from some form of the condition, which takes many forms.

Effective treatments for long COVID have not yet been identified because the causes are still being investigated and symptoms can vary greatly from person to person.

Other emerging research points to a number of factors that may contribute to long COVID. One study published last month in the journal Nature found that people with long COVID appear to have lower levels of the stress hormone cortisol, which regulates alertness and helps people wake up. This could explain why many people with long COVID complain of fatigue.

The same study found that some people with long COVID have compromised immune systems as a result of never fully clearing the virus from their bodies. The body's ongoing effort to eliminate it could be allowing other dormant viruses to resurface, potentially causing some of the symptoms linked to long COVID.

"Clinicians treating patients with long COVID have been relying on personal reports from those patients to determine if their symptoms are improving," said Dr. Sara Cherry, coauthor of the Penn study. "Now, our research shows that there are biomarkers we may be able to use to match patients to treatments or clinical trials that address the specific causes of their long COVID symptoms, and more effectively assess their progress."

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