Emily Harris, JAMA. Published online November 1, 2023. doi:10.1001/jama.2023.21170

A study linking viral infection with reduced levels of serotonin, a neurotransmitter involved in learning, memory, and mood, has proposed a new potential mechanism underlying post–COVID-19 condition. Also known as long COVID, the condition involves symptoms such as fatigue, memory loss, and cognitive impairment.

Using results from human participants, mice, and organoid cultures, the researchers found that long COVID was tied with a decline in serotonin. A viral reservoir in the gut appeared to trigger inflammation that decreased intestinal absorption of tryptophan, serotonin’s precursor molecule.

Serotonin activity supports vagus nerve function, among other roles. In the study, serotonin loss was associated with lower nerve activity. Dysfunction in the vagus nerve was linked with characteristic long COVID symptoms such as memory loss and hippocampal dysfunction.

“Clinicians treating patients with long COVID have been relying on personal reports from those patients to determine if their symptoms are improving,” Sara Cherry, PhD, an author of the study published in Cell, said in a statement. “Now, our research shows that there are biomarkers we may be able to use to match patients to treatments or clinical trials.”