Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms
Gastroenterology, 2021
Livanos A., Jha D., Cossarini F., Gonzalez-Reiche A., Tokuyama M., Aydillo T., Parigi T., Ladinsky M., Ramos I., Dunleavy K., Lee B., Dixon R., Chen S., Martinez-Delgado G., Nagula S., Bruce E., Ko H., Glicksberg B., Nadkarni G., Pujadas E., Reidy J., Naymagon S., Grinspan A., Ahmad J., Tankelevich M., Bram Y., Gordon R., Sharma K., Houldsworth J., Britton G., Chen-Liaw A., Spindler M., Plitt T., Wang P., Cerutti A., Faith J., Colombel J., Kenigsberg E., Argmann C., Merad M., Gnjatic S., Harpaz N., Danese S., Cordon-Cardo C., Rahman A., Schwartz R., Kumta N., Aghemo A., Bjorkman P., Petralia F., van Bakel H., Garcia-Sastre A., Mehandru S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
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.