Associations Between Gastrointestinal Symptoms and COVID-19 Severity Outcomes Based on a Propensity Score-Weighted Analysis of a Nationwide Cohort

Background and aims: Gastrointestinal (GI) symptoms are well-recognized manifestations of coronavirus disease 2019 (COVID-19). Our primary objective was to evaluate the association between GI symptoms and COVID-19 severity.

Methods: In this nationwide cohort of US veterans, we evaluated GI symptoms (nausea/vomiting/diarrhea) reported 30 days before and including the date of positive SARS-CoV-2 testing (March 1, 2020, to February 20, 2021). All patients had ≥1 year of prior baseline data and ≥60 days follow-up relative to the test date. We used propensity score (PS)-weighting to balance covariates in patients with vs without GI symptoms. The primary composite outcome was severe COVID-19, defined as hospital admission, intensive care unit admission, mechanical ventilation, or death within 60 days of positive testing.

Results: Of 218,045 SARS-CoV-2 positive patients, 29,257 (13.4%) had GI symptoms. After PS weighting, all covariates were balanced. In the PS-weighted cohort, patients with vs without GI symptoms had severe COVID-19 more often (29.0% vs 17.1%; P < .001). When restricted to hospitalized patients (14.9%; n=32,430), patients with GI symptoms had similar frequencies of intensive care unit admission and mechanical ventilation compared with patients without symptoms. There was a significant age interaction; among hospitalized patients aged ≥70 years, lower COVID-19-associated mortality was observed in patients with vs without GI symptoms, even after accounting for COVID-19-specific medical treatments.

Conclusion: In the largest integrated US health care system, SARS-CoV-2-positive patients with GI symptoms experienced severe COVID-19 outcomes more often than those without symptoms. Additional research on COVID-19-associated GI symptoms may inform preventive efforts and interventions to reduce severe COVID-19.