A new possible explanation for long COVID could lead to a simple treatment for some patients

That’s according to a new study by University of Pennsylvania researchers published Monday in the journal Cell. Researchers say the findings could lead to a treatment for a disease that so far has none.

The idea of SARS-CoV-2, or any coronavirus, lingering in the body after acute infection—in what’s called a “viral reservoir,” sometimes referred to in the popular press as “viral ghosts”—is not new. In fact, it’s been proven to occur, with some speculating that viral reservoirs are responsible for long COVID symptoms in at least some cases. Other mechanisms behind long COVID are thought to include chronic inflammation, increased prevalence of blood clots, and autonomic dysfunction—all triggered by the virus.

While it might seem logical that neurologic long COVID symptoms like brain fog, memory loss, and depression are caused by the presence of virus in the brain, researchers in Pennsylvania propose a different theory: that virus lingering in the gut causes such symptoms in a round-about way.

It works like this: SARS-CoV-2 lingering in the gut causes persistent inflammation, which leads to reduced production of serotonin—a neurotransmitter that sends messages between nerve cells in your brain and those in other parts of the body. It also plays a key role in regulating sleep, mood, digestion, and blood clotting, among other bodily functions. 

The lack of serotonin, in turn, disrupts connectivity between the peripheral nervous system and the brain, causing neurologic symptoms. The gut is often called the “second brain” because both are large nerve centers in constant communication with each other.

“Long COVID varies in each individual patient, and we don’t fully understand what causes the differences in symptoms from patient to patient,” Christoph Thaiss, an assistant professor of microbiology at the University of Pennsylvania’s Perelman School of Medicine, said in a news release about the study.

But the study offers doctors a biomarker they can test patients for—serotonin—he added, and the ability to treat low levels with supplementation or SSRIs, antidepressants that inhibit the reabsorption of serotonin by neurons, thus increasing its availability.

So far, there is no specific, effective treatment for long COVID. This could be the first, or one of them.

What is long COVID?

Many experts contend that long COVID is best defined as a chronic-fatigue-syndrome-like condition that develops after COVID illness, similar to other post-viral syndromes that can occur after infection with herpes, Lyme disease, and even Ebola. Other post-COVID complications, like organ damage and post–intensive-care syndrome, should not be defined as long COVID, they say.

Common symptoms include memory loss, brain fog, fatigue, and depression, though more than 200 symptoms have been reported.

Anywhere from 7.7 million to 23 million Americans were estimated to have long COVID as of July, according to the U.S. Department of Health and Human Services. Damage from the new disorder can linger for at least two years, according to a study published in August in Nature Medicine.