New Information Helps Explain Long COVID’s Influence on the Brain


Post-acute sequelae of SARS-CoV-2 infection is also referred to as long COVID. This condition has become a major health concern because the pathophysiology is presently unknown and there are no effective treatments available. In addition, the complexity of this condition is illustrated by how it can negatively and profoundly impact major body systems, including the heart, immune system, and brain. Fortunately, research in this area is growing, including a new study on brain function featured in the journal Cell.

The Serotonin Connection

The study set out to determine if there were any differences in circulating amino acids and their derivatives between people with long COVID-19 and people who overcame acute COVID-19. Using metabolomics, they found that there was low circulating serotonin in those with long COVID but not in those who overcame the infection. 

The authors describe three mechanisms that explain the serotonin reduction:

  1. Diminished uptake of tryptophan, a serotonin precursor, in the gut.
  2. Reduced serotonin storage in platelets.
  3. Faster serotonin turnover by serotonin-metabolizing enzymes.

“This study showed that viral RNA remnants persist in the gut of those with long COVID, which stimulates interferon production," explains Tina Kaczor, ND, FABNO, Editor-in-Chief of the Natural Medicine Journal. “The interferon stimulation is affecting serotonin on three different fronts.”

As indicated by this study, serotonin reduction impedes vagus nerve activity which impairs hippocampal responses and memory.

“Brain fog is a common long COVID symptom, and, interestingly, the authors determined that serotonin levels within the brain may not explain the brain fog,” said Kaczor, who is the creator of “Rather, the brain fog of long COVID is likely due to direct gut-brain communication via the vagus nerve, which is surprising because we concentrate on serotonin's effect at the synapses in the brain, but in this case, that's not the mechanism."

A study from earlier this year looked at mental health issues associated with long COVID including increased depression and anxiety and decreased life satisfaction. This new information about serotonin decline via the gut-brain connection may help create treatment protocols for those individuals as well.

Healing the Long COVID Brain

Regarding an integrative approach to treating long COVID brain issues, Kaczor feels it’s more about gut health than serotonin. Conventional medicine will likely consider utilizing medications to treat this condition; however, that won’t address the underlying cause, which is a core tenet of integrative medicine.

“This study suggests that the only way to improve circulating serotonin levels is to heal the gut and clear the viral RNA remnants that are causing the problem," she said. "Meanwhile, for some symptom relief, you may be able to bypass the poor absorption of tryptophan by using 5-HTP while you work on healing the gut." Kaczor explained that the study did not use 5-HTP; the researchers used a dipeptide tryptophane-glycine to bypass the inability to absorb the tryptophan through its transporter.

Once gut health is restored and there is enough tryptophan available to synthesize serotonin, natural serotonin boosters can be utilized as well.

“Natural ways to raise serotonin levels include getting outside in sunlight, exercising, laughing, socializing, and recalling happy memories,” said Kaczor. “Cofactors needed for serotonin production are essential and include vitamins B3 and B6, zinc, and magnesium.”

Nutrition is also critical to brain function. A cross-sectional study from earlier this year showed that eating a plant-based diet was associated with a lower risk of hospitalization and the development of severe COVID. A review also published this year confirmed the brain health benefits of the Mediterranean diet as a means to reduce cognitive decline via the gut-brain axis. Research demonstrates that the Mediterranean diet is associated with healthy aging and better mental health.

“Through a combination of diet, lifestyle, and targeted nutrients and herbs, integrative practitioners are well-equipped to assist patients struggling with long COVID,” concluded Kaczor.

To listen to a podcast about long COVID featuring Dr. Kaczor and two other experts, click here.