Single-cell gene expression links SARS-CoV-2 infection and gut serotonin

We read with great interest the paper by Ha et al demonstrating that circulating levels of serotonin (5-hydroxytryptamine, 5-HT) are increased in COVID-19 and correlate with disease severity and gastrointestinal symptoms such as diarrhoea. Another recent paper by Lin et al in this journal demonstrated that diarrhoea is the most common GI symptom in patients with COVID-19. Almost all 5-HT in our body is produced by enterochromaffin (EC) cells within the epithelium of the GI tract, which constitute approximately half of all enteroendocrine (EE) cells. Gut-derived 5-HT modulates gut peristalsis and exacerbates inflammatory responses by acting as a chemotactic molecule for various immune cells and by triggering cytokine release. While most gut epithelial cell types are susceptible to SARS-CoV-2 infection, EE cells have the greatest proportion of cells infected at 12 hours after viral exposure.