Low Serotonin Levels Could Explain Long COVID Brain Fog

Researchers suggest that SARS-CoV-2 infection can cause serotonin levels to drop, leading to ongoing symptoms associated with long COVID.

Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a mysterious condition that causes a wide array of symptoms, including tiredness, muscle and joint aches, and problems with cognition, which can manifest as something known as "brain fog." These symptoms can last for 12 to 18 months, which can significantly impact a person's daily activities.

The U.S. Government Accountability Office estimates that approximately 7.7 to 23 million Americans have experienced long COVID. This number could be larger or smaller, as many of these cases are self-reported, and some people are never diagnosed.

Scientists have different theories about why long COVID occurs. These include viral persistence, chronic inflammation, problems with the autonomic nervous system, or blood clotting issues.

In a study published on October 16 in the journal Cell, scientists suggest these theories are connected and are part of a process that reduces serotonin in the body.

To conduct the research, University of Pennsylvania scientists analyzed metabolites in the blood of 58 individuals with long COVID, 60 people with COVID-19, and 30 individuals who had recovered from the disease. They also recreated infection and viral persistence in animal models.

The team found that participants with long COVID had significantly lower levels of serotonin in the body, with the lowest levels observed in participants with numerous long COVID symptoms. What's more, stool samples revealed that some individuals still had SARS-CoV-2 in their gastrointestinal tracts.

The researchers say the presence of viral RNA and elevated interferon activity are likely mechanisms behind the reduced serotonin levels observed in the analysis.

Interferons are immune system proteins that fight infections. These proteins initiate interferon activity, resulting in inflammation in the gastrointestinal tract. This inflammation reduces tryptophan, which is a serotonin precursor.

The researchers say interferon-driven inflammation can also lead to platelet problems that impact serotonin storage and speed up the breakdown of serotonin.

When serotonin levels go down, it can affect part of the autonomic nervous system called the vagus nerve — which can negatively impact memory and brain functions. This might explain why people with long COVID experience problems with memory and thinking.

Though more investigations are needed, the scientists say their findings show a potential treatment route for people with long COVID.

Specifically, they point out animal studies that have demonstrated supplementing with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs) can potentially restore serotonin levels and reverse memory issues.

If human studies delivered the same results, it could open the door to new long COVID treatment options using medications that already exist.