• Alexandra E Livanos, Divya Jha, Francesca Cossarini, Ana S Gonzalez-Reiche, Minami Tokuyama, Teresa Aydillo, Tommaso L Parigi, Mark S Ladinsky, Irene Ramos, Katie Dunleavy, Brian Lee, Rebekah E Dixon, Steven T Chen, Gustavo Martinez-Delgado, Satish Nagula, Emily A Bruce, Huaibin M Ko, Benjamin S Glicksberg, 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 Colombel, 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, and Saurabh Mehandru.
• Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
• Gastroenterology. 2021 Jun 1; 160 (7): 2435-2450.e34.

Background & AimsGiven 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.MethodsHuman 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.ResultsCOVID-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.ConclusionsThese 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.Copyright © 2021 AGA Institute. All rights reserved.

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