Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms.

Abstract Background and Aims Given gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance. Methods Human intestinal biopsy tissues were obtained from COVID-19 patients (n=19) and uninfected controls (n=10) for microscopic examination, CyTOF analyses and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in two large, independent cohorts of hospitalized patients in the United States (n=634) and Europe (n=287) using multivariate logistic regressions. Results COVID-19 cases and controls in the biopsy cohort were comparable for age, gender, rates of hospitalization and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy, in 14 of 16 patients studied. High dimensional analyses of GI tissues revealed low levels of inflammation, including downregulation of key inflammatory genes including IFNG, CXCL8, CXCL2 and IL1B and reduced frequencies of proinflammatory dendritic cells compared with controls. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of gender, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms. Conclusion These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in COVID-19 patients presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2 associated inflammation needs to be further examined.