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

Livanos, Alexandra E.; Cerutti, Andrea, 1965-; Mehandru, Saurabh

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

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dc.contributor.author Livanos, Alexandra E.
dc.contributor.author Cerutti, Andrea, 1965-
dc.contributor.author Mehandru, Saurabh
dc.date.accessioned 2021-06-17T06:17:41Z
dc.date.issued 2021
dc.description.abstract 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.
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dc.identifier.citation Livanos AE, Jha D, Cossarini F, Gonzalez-Reiche AS, Tokuyama M, Aydillo T et al. Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms. Gastroenterology. 2021;160(7):2435-50.e34. DOI: 10.1053/j.gastro.2021.02.056
dc.identifier.doi http://dx.doi.org/10.1053/j.gastro.2021.02.056
dc.identifier.issn 0016-5085
dc.identifier.uri http://hdl.handle.net/10230/47910
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Gastroenterology. 2021;160(7):2435-50.e34
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.keyword COVID-19
dc.subject.keyword GI infection
dc.subject.keyword GI symptoms
dc.subject.keyword SARS-CoV-2
dc.subject.keyword Host immune response
dc.subject.keyword Outcomes
dc.title Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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