Boosting serotonin may repair memory loss in long Covid patients: study

Persistent inflammation in long Covid patients has been linked to depleting serotonin levels and in turn, several symptoms such as brain fog, fatigue, and memory loss.

Researchers at the United States' University of Pennsylvania's School of Medicine found that the stool samples of some long Covid patients showed traces of the Covid-causing virus SARS-CoV-2 months after acute infection.

They found that these remaining viral particles triggered the immune system to release virus-fighting proteins called interferons, which produce inflammation in the gastrointestinal (GI) tract.

This inflammation in the GI tract reduces the absorption of the amino acid tryptophan, which is a building block for several neurotransmitters (brain chemicals), including serotonin.

Serotonin, primarily produced in the GI tract, plays a key role in regulating memory, sleep, digestion, wound healing, and other functions that maintain a metabolic balance within the body.

Serotonin also regulates the vagus nerve, a system of neurons that mediates the communication between the body and the brain.

The researchers found that a reduced tryptophan absorption due to inflammation in the GI tract led to depletion in serotonin levels, resulting in a disrupted vagus nerve signalling.

This disrupted signalling between the body and the brain can cause several long Covid symptoms, such as memory loss in the months or years following infection, they said in their study published in the journal Cell.

"Clinicians treating patients with long Covid have been relying on personal reports from those patients to determine if their symptoms are improving. 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," said co-senior author Sara Cherry, a professor of pathology and laboratory medicine.

Using small animal models, the researchers could demonstrate that restoring serotonin levels by treating them with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs) could reverse memory impairment.

SSRIs enhance serotonin levels in the body by limiting its reabsorption at neuron interconnections and are thus used as antidepressants for treating major depressive disorder, anxiety disorders, and other psychological conditions.

"There has been some evidence to suggest that SSRIs 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 co-senior author Benjamin Abramoff, director of the Post-COVID Assessment and Recovery Clinic, and an assistant professor of clinical physical medicine.

The researchers also said uncovering these mechanisms presents more opportunities for additional research into the other processes that tryptophan influences