Andrea Wong (Mentor: Maayan Levy, PhD)

“Viral infection suppresses serotonin production”

Andrea C. Wong, Jonathan Perla, Patrick Lundgren, Lenka Dohnalová, Hélène C. Descamps, Oxana Dmitrieva-Posocco, Bhoomi Madhu, Timothy Cox, Benjamin Abramoff, Sara Cherry, Christoph A. Thaiss and Maayan Levy

The COVID-19 pandemic has been one of the most severe global health crises of the 21st century. While vaccine availability has decreased mortality rates in some areas of the world, many unvaccinated individuals are still suffering from COVID-19 infection. Furthermore, patients who were previously infected with SARS-CoV-2 are now suffering from long-term consequences of COVID-19 infection many months after resolution of acute symptoms, termed “long COVID”. Long COVID symptoms include shortness of breath, heart palpitations, deep fatigue, mood changes, “brain fog”, and sleep disturbances. Depression and anxiety are also common symptoms reported with acute COVID-19. The psychological symptoms associated with acute COVID-19 infection are incompletely understood, and the underlying causes of long COVID are completely unknown. We found that patients with COVID-19 have reduced serotonin levels compared to patients who have fully recovered from COVID-19. Serotonin plays an important role in regulating mood, sleep, appetite, gastrointestinal function, heart functions, and many other physiological processes. While serotonin levels are restored in patients who have recovered from COVID-19, preliminary data from our lab suggests that patients who are experiencing long-term symptoms of COVID-19 show no recovery of serotonin levels.

About 95% of the body’s serotonin is produced by enteroendocrine cells in the gut. Serotonin is produced from the essential amino acid, tryptophan. We set out to investigate how SARS-CoV-2 infection causes decreases in serotonin levels. We found that exposure to synthetic double stranded RNA in the form of poly(I:C) alone is sufficient to decrease serotonin levels. Poly(I:C) administration results in decreased ACE2 and SLC6A19 transcription, both of which control tryptophan uptake in the gut. Furthermore, poly(I:C) exposure results in decreased TPH1 transcription, which is the rate-limiting enzyme for serotonin production from tryptophan. Administration of the serotonin precursor, 5-hydroxy-L-tryptophan is sufficient to rescue this effect. Collectively, this data suggests that dsRNA produced during viral infection can result in decreased serotonin levels which may explain some of the symptoms of COVID-19.