Long COVID's Critical Pattern May Have Been Found

 

A recent study has identified a pathway that connects multiple potential causes of the debilitating disorder by pointing to decreased levels of a well-known chemical messenger in persons with lengthy COVID.

Immunologist Andrea Wong and colleagues from the University of Pennsylvania set out to identify different molecular alterations that would account for the confusing array of up to 200 potential symptoms that persons with chronic COVID may experience.

Since the beginning of the pandemic, much progress has been made in understanding the potential causes of protracted COVID, which can persist for months or even years after an acute SARS-CoV-2 infection has subsided.

However, this expanding body of evidence also paints a somewhat confusing picture of interrelated, underlying causes: elevated blood clotting, a persistent virus, ongoing inflammation, and a malfunctioning neurological system are just a few of the working hypotheses seeking to explain the emergence of protracted COVID.

Four of those are suggested by this latest study's findings.

Serotonin, a chemical messenger most known for its role in elevating mood, as well as other activities linked to memory, cognition, and sleep, was decreased in those with extended COVID. Additionally, long distance travelers pass on virus leftovers in their feces.

The team next pieced together a potential pathway connecting a lack of serotonin in the stomach, where most serotonin is typically produced, to its effects in the brain using a combination of animal models and organoid cultures.

They suggest a link between persistent viral material and the immune system's production of interferons, a class of signaling proteins involved in the body's antiviral defenses.

This promotes inflammation, which restricts the gut's ability to absorb tryptophan, an amino acid used in the production of serotonin.

The platelets, blood cells involved in blood clotting that also transport serotonin throughout the body, are affected by chronic inflammation.

The vagus nerve, the body's communication superhighway that carries information from the brain to the gut and other organs, becomes less active as a result of lower levels of circulating serotonin.Our findings imply that a single pathway that is connected by serotonin may connect a number of the existing theories for the pathophysiology of protracted COVID (viral reservoir, chronic inflammation, hypercoagulability, and vagus nerve dysfunction).

A viral infection in mice caused low serotonin levels and decreased vagus nerve activity, which caused the animals to perform worse on memory tests.

Amazingly, however, restoring serotonin levels allowed for the prevention of those memory problems, which approximate but do not exactly duplicate the cognitive issues seen by long-haul drivers.

To put those theories to the test, more human research are required. Future studies should address the question of why some COVID patients in a second cohort, some of whom may have had lesser symptoms, did not have low serotonin levels.

"We hope that our discovery will inspire clinical studies that use these insights to develop new tools for the diagnosis, monitoring, and treatment of long COVID," Levy stated. "They are so urgently needed."

The study was released in the journal Cell.