Patients With COVID-19 and Gastrointestinal Symptoms Have Significantly Reduced Mortality

A man experiencing stomach pain
Researchers analyzed the impact of GI symptoms on COVID-19 disease outcomes and patients’ inflammatory responses.

Patients with COVID-19 and gastrointestinal (GI) symptoms have a significant reduction in disease-associated mortality, according to research presented at Digestive Disease Week 2021.

The study included 2 independent cohorts of patients with COVID-19 who were hospitalized in the United States (n = 634) and in Italy (n = 287). Investigators evaluated patients’ GI symptoms at admission and related them to mortality and circulating proteomic biomarkers. Disease severity, which was defined by oxygenation and end organ damage, was also assessed in the US cohort.

Multivariate logistic regression was conducted in both cohorts to determine the association of GI symptoms, such as nausea, vomiting, and diarrhea, at admission and outcomes after adjustment for age, sex, and comorbid diseases.

A prediction model was developed based on the original US cohort and validated against a distinct US cohort (n = 242). In a subset of 238 patients, circulating cytokines and chemokines were assessed with a multiplexed proteomic assay, which quantified 92 protein analytes.

The researchers found a significant reduction in disease-associated mortality in patients with COVID-19 who presented with GI symptoms in the US cohort (odds ratio [OR], 0.54; 95% CI, 0.34-0.86) and in the Italian cohort (OR, 0.33; 95% CI, 0.13-0.67), independent of age, sex, and comorbidities.

The prediction model that included age, body mass index (BMI), and GI symptoms had a significantly improved ability to predict disease severity and mortality compared with age and BMI alone—median area under the curve (AUC), 0.64 (age + BMI + GI symptoms) versus 0.59 (age + BMI) for disease severity, and 0.73 (age + BMI + GI symptoms) versus 0.70 (age + BMI) for mortality.

The proteomic analysis detected 6 clusters based on their co-segregation among all patients. In patients with diarrhea, clusters 4 and 5, which were enriched in the “Hallmark Inflammatory Response” and “KEGG JAK/STAT Signaling Pathway,” respectively, were decreased.

The reduced mortality in patients with COVID-19 presenting with GI symptoms was associated with lower circulating levels of key inflammatory proteins, including interleukin (IL)-6, IL-8, IL-17A, and chemokine [C-C motif] 28 (CCL28), which are associated with poor outcomes in COVID-19, the study authors noted. An increase was observed in IL-7 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which are involved in immunoregulatory functions.

“These data highlight GI involvement as an important parameter for severity stratification in COVID-19 and point toward an immunomodulatory role of the GI tract in response to SARS-CoV-2 infection,” concluded the researchers.


Livanos AE, Cossarini F, Parigi T, et al. Significantly reduced mortality in COVID-19 patients with gastrointestinal manifestations. Poster presented at: Digestive Disease Week Annual Meeting; May 21-23, 2021. Abstract Fr492.

This article originally appeared on Gastroenterology Advisor