Unlocking brain fog: is it serotonin?

STAT reports on a new study that might be getting to the root of the long-covid brain fog, finding that the symptom appears to go hand-in-hand with a lack of free-floating serotonin in the body:

A team led by researchers from the University of Pennsylvania concludes that when long Covid depletes peripheral serotonin — the kind that circulates in our bodies and not just the brain — that deficit impairs memory and other brain functions. The authors hope further research will lead to testing potential treatments.

“These effects can explain a wide spectrum of symptoms that our patients with long Covid have. It certainly points us in a direction of the underlying root causes,” Benjamin Abramoff, director of Penn Medicine’s Post-COVID Assessment and Recovery Clinic and a study co-author, said in an interview.

The mechanisms are also linked to excessive blood clotting and autonomic dysfunction, in which the nervous system can’t control processes like heart rate or blood pressure. “We found that it’s really across the board that these decreases of serotonin are noted, so it’s not only in those with neurocognitive effects, but also with pulmonary effects and cardiovascular dysfunction,” Abramoff said. “It seems to be a universal phenomenon.”

The research rests on an analysis of metabolites in the blood that compared people with long Covid to people who recovered completely, as well as animal models recreating infection and viral persistence. Serotonin levels were markedly lower in long Covid patients, likely driven by elevated interferon levels. Some long Covid patients still had some virus in stool samples, indicating reservoirs in their gastrointestinal tracts. That’s where interferons, proteins released by the immune system to fight the virus, set off inflammation that cuts down levels of a serotonin precursor, the amino acid tryptophan.

Low serotonin levels weaken vagus nerve signaling, the gut-brain connection that could explain neurocognitive problems that are one hallmark of long Covid. Serotonin signaling can also affect blood clotting, the GI tract, and the central nervous system, making it one of the most important neurotransmitters in the body, not just in the brain where it can be involved in anxiety and depression. The more long Covid symptoms patients had, the lower their peripheral serotonin levels, the study found.

You can read more of the Penn study here, in Cell.