SARS-CoV-2-specific IgA and limited inflammatory cytokines are present in the stool of select patients with acute COVID-19

Britton, Graham J.; Chen-Liaw, Alice; Cossarini, Francesca; Livanos, Alexandra E.; Spindler, Matthew P.; Plitt, Tamar; Eggers, Joseph; Mogno, Ilaria; Gonzalez-Reiche, Ana S.; Siu, Sophia; Tankelevich, Michael; Grinspan, Lauren Tal; Dixon, Rebekah E.; Jha, Divya; Martinez-Delgado, Gustavo; Amanat, Fatima; Hoagland, Daisy A.; tenOever, Benjamin R.; Dubinsky, Marla C.; Merad, Miriam; van Bakel, Harm; Krammer, Florian; Bongers, Gerold; Mehandru, Saurabh; Faith, Jeremiah J.

BACKGROUND AND AIMS: Immune dysregulation caused by SARS-CoV-2 infection is thought to play a pathogenic role in COVID-19. SARS-CoV-2 can infect a variety of host cells, including intestinal epithelial cells. We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. METHODS: We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool and serum samples from a prospectively enrolled cohort of 44 hospitalized COVID-19 patients. RESULTS: SARS-CoV-2 RNA was detected in stool of 41% of patients and was found more frequently in patients with diarrhea than those without (16[44%] vs 5[19%], p=0.06). Patients who survived had lower median viral genome copies than those who did not (p=0.021). Compared to uninfected controls, COVID-19 patients had higher median fecal levels of IL-8 (166.5 vs 286.5 pg/mg; p=0.05) and lower levels of fecal IL-10 (678 vs 194 pg/mg; p<0.001) compared to uninfected controls. Stool IL-23 was higher in patients with more severe COVID-19 disease (223.8 vs 86.6 pg/mg; p=0.03) and we find evidence of intestinal virus-specific IgA responses, which was associated with more severe disease. Fecal cytokines and calprotectin levels were not correlated with gastrointestinal symptoms or with the level of virus detected. CONCLUSIONS: Although SARS-CoV-2 RNA was detectable in the stools of COVID-19 patients and select individuals had evidence for a specific mucosal IgA response, intestinal inflammation was limited, even in patients presenting with gastrointestinal symptoms.