Gastrointestinal Symptoms are Quantitatively and Biologically Associated with COVID-19 Severity

Abstract

Background: Gastrointestinal (GI) symptoms have been reported variously in patients with coronavirus disease 2019 (COVID-19). However, whether GI symptoms are associated with critical illness remain inconclusive.Methods: We performed a large-scale meta-analysis to comprehensively quantify the prevalence of various GI symptoms and their associations with COVID-19 severity. Single-cell transcriptome and SARS-CoV-2 pseudovirus infection assay were performed to elucidate potential mechanisms. A total of 55 studies encompassing 14,361 cases were included in this meta-analysis.Findings: We found that anorexia was the most common GI symptom in COVID-19 patients with a pooled prevalence of 19.93%. Patients with GI symptoms of abdominal pain, anorexia, and diarrhea have 2.78, 2.05, and 1.25 times risks to develop COVID-19 severity, respectively. Notably, male patients with GI symptoms were more susceptible to severe COVID-19 than females with risk increased by 47%. The proportion of angiotensin-covering enzyme II (ACE2)-positive cells in intestinal epithelial cells was the highest compared with that in other GI organs. Biologically, elevated expression of ACE2 in intestinal epithelial cells could promote SARS-CoV-2 colonization in accordance with the occurrence of GI symptoms in the clinical course of COVID-19.Interpretation: Timely recognition of COVID-19 patients with GI symptoms in the early stage of infection may reduce the risk of developing severe illness.Funding: None to declare. Declaration of Interest: None to declare.