Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms

• DOI: 10.1053/j.gastro.2021.02.056
• Publication Date: 2021-03-04T20:43:53Z
• Authors: Alexandra E. Livanos; Divya Jha; Francesca Cossarini; Ana S. Gonzalez-R...; Minami Tokuyama; Teresa Aydillo; Tommaso L. Parigi; Mark S. Ladinsky; Irene Ramos; Katie Dunleavy; Brian Lee; Rebekah E. Dixon; Steven T. Chen; Gustavo Martinez-...; Satish Nagula; Emily A. Bruce; Huaibin M. Ko; Benjamin S. Glick...; Girish Nadkarni; Elisabet Pujadas; Jason Reidy; Steven Naymagon; Ari Grinspan; Jawad Ahmad; Michael Tankelevich; Yaron Bram; Ronald Gordon; Keshav Sharma; Jane Houldsworth; Graham J. Britton; Alice Chen-Liaw; Matthew P. Spindler; Tamar Plitt; Pei Wang; Andrea Cerutti; Jeremiah J. Faith; Jean-Frederic Col...; Ephraim Kenigsberg; Carmen Argmann; Miriam Merad; Sacha Gnjatic; Noam Harpaz; Silvio Danese; Carlos Cordon-Cardo; Adeeb Rahman; Robert E. Schwartz; Nikhil A. Kumta; Alessio Aghemo; Pamela J. Bjorkman; Francesca Petralia; Harm van Bakel; Adolfo Garcia-Sastre; Saurabh Mehandru
• Keywords: Proinflammatory cytokine; Pathogenesis

(Uploaded by Plazi for the Bat Literature Project) Background & Aims Given that 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 patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions. Results COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, 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. Conclusions These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 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.