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

Gastroenterology. 2021 Jun;160(7):2435-2450.e34. doi: 10.1053/j.gastro.2021.02.056. Epub 2021 Mar 4.


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.

Keywords: COVID-19; GI infection; GI symptoms; SARS-CoV-2; host immune response; outcomes.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / diagnosis
  • COVID-19 / immunology
  • COVID-19 / mortality
  • COVID-19 / virology*
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / blood
  • Female
  • Gastrointestinal Diseases / diagnosis
  • Gastrointestinal Diseases / immunology
  • Gastrointestinal Diseases / mortality
  • Gastrointestinal Diseases / virology*
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Mucosal*
  • Inflammation Mediators / blood
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / virology*
  • Italy
  • Male
  • Middle Aged
  • New York City
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Viral Load


  • Cytokines
  • Inflammation Mediators