Diarrhea as an Independent Risk Factor for COVID-19 Severity and Inpatient Mortality

ABSTRACT

Introduction: Multiple meta-analyses have shown that over 15% patients with COVID-19 have at least one gastrointestinal complaint, most commonly diarrhea. The effects on the gastrointestinal system are thought to be mediated by the high expression of angiotensin-converting enzyme 2 (ACE2) and cellular serine proteases (TMPRSS2) in enterocytes, which cause altered intestinal permeability. The purpose of this study was to determine the incidence of diarrhea as it relates to COVID-19 infection and to determine if having concomitant diarrhea had a significant impact on disease course. Method(s) A retrospective chart review of 164,730 patients in a hospital system who were older than 18 years of age and had a positive SARS-CoV-2 test from March 2020 to February 2022 was completed. Diarrhea was determined using ICD code or patient's symptoms. Patients with confounding variables such as IBD, IBS, Celiac, Clostridium difficile, and pancreatic insufficiency were excluded. Demographic clinical characteristics and outcomes, including inpatient admission and mortality, were compared in patients with and without diarrhea. The Mann-Whitney test and Fisher's exact or Chi-square test was used for continuous and categorical variables respectively and multivariate logistic regression was used to evaluate for significant differences in disease outcome between the two groups. (Table) Results: Of the 164,730 patients included, 14,648 (8.89%) had diarrhea at the time of SARS-CoV-2. 6,748/33,464 (20.16%) of inpatient admissions were associated with diarrhea. On multivariate analysis, diarrhea was an independent risk factor for inpatient hospitalization (OR 2.39, CI 95% 2.28-2.51, P, 0.001) and inpatient mortality (OR 1.15, CI 96% 1.06-1.26, P= 0.001) after controlling for age, gender, race, comorbidities that could impact patient outcome, use of immunomodulators and outpatient antibiotics. Conclusion(s) These findings show that, even with controlling for comorbidities with COVID-19, diarrhea was an independent factor for predicting inpatient mortality and inpatient admission in general. Patients who had diarrhea and COVID-19 were sicker, having more comorbid conditions than those without diarrhea in our cohort. Attention should be given to not only respiratory complaints of COVID-19, but also gastrointestinal complaints, as they are an indicator of poor prognosis and mortality.