Gastrointestinal Manifestations and Outcomes of COVID-19: A Comprehensive Systematic Review and Meta-analysis

Abstract

Introduction Pulmonary symptoms are the most prominent manifestations of Coronavirus disease 2019 (COVID-19). However, gastrointestinal (GI) symptoms have been reported widely as well. Literature describing the relation of these symptoms with outcomes of COVID-19 patients is limited in terms of sample size, geographic diversity, and the spectrum of GI symptoms included. We aim to evaluate the association of GI symptoms with outcomes of hospitalized COVID-19 patients. Methods A systematic review and meta-analysis of observational studies assessing GI symptoms and outcomes in COVID-19 patients were undertaken using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. Details on outcomes included ICU vs. non-ICU admission, severe vs. non-severe disease, invasive mechanical ventilation (IMV) vs. no-IMV use, oxygen saturation <90% vs. >90%, in-hospital mortality vs. discharged alive and survivors. We obtained the odds ratio (OR), 95% confidence interval (95%CI), and forest plots. Sensitivity analysis was used to analyze publication bias and heterogeneity. Results In 35 studies with 7931 confirmed COVID-19 patients, we found that anorexia (pooled OR:2.05; 95%CI: 1.36-3.09, p=0.0006) and abdominal pain (OR 2.80; 95%CI: 1.41-5.54, p=0.003) were associated with a higher risk of poor outcomes and no such association was found for diarrhea (OR 1.04; 95%CI: 0.85-1.26, p=0.71), nausea (OR 0.73; 95%CI: 0.38-1.39, p=0.34) and vomiting (OR 1.24; 95%CI 0.86-1.79, p=0.25). Conclusion The meta-analysis concludes that anorexia and abdominal pain are associated with poor outcomes in hospitalized COVID-19 patients, while diarrhea, nausea, and vomiting have no association. Future research should focus on whether detecting GI invasion in conjunction with fecal polymerase chain reaction (PCR) testing can aid in the early triage of high-risk individuals and improve outcomes.

Keywords: abdominal pain; anorexia; covid-19; diarrhea; gastrointestinal symptoms; nausea; outcomes; vomiting.

Figure 1. Flow diagram of literature search and study selection process

COVID-19: coronavirus disease 2019; SARS-CoV-2: severe acute respiratory syndrome-coronavirus-2

Figure 2. Forest plot showing the association of diarrhea with outcomes in COVID-19 hospitalized patients

References: [43-45,47-77] COVID-19: coronavirus disease 2019

Figure 3. Forest plot showing the association of nausea with outcomes in COVID-19 hospitalized patients

References: [45,47,49,51,53,60,70,71,73,77] COVID-19: coronavirus disease 2019

Figure 4. Forest plot showing the association of nausea with outcomes in COVID-19 hospitalized patients (after sensitivity analysis)

References: [45,47,49,51,53,60,70,71,73,77] COVID-19: coronavirus disease 2019

Figure 5. Funnel Plot showing the association of nausea with outcomes in COVID-19 hospitalized patients

COVID-19: coronavirus disease 2019

Figure 6. Forest plot showing the association of vomiting with outcomes in COVID-19 hospitalized patients

References: [45-47,49-50,60,62-63,70-71,74,77] COVID-19: coronavirus disease 2019

Figure 7. Forest plot showing the association of anorexia with outcomes in COVID-19 hospitalized patients

References: [45,47,49,51,54,63,65,67,68,70-72,76] COVID-19: coronavirus disease 2019

Figure 8. Forest plot showing the association of anorexia with outcomes in COVID-19 hospitalized patients (after sensitivity analysis)

References: [45,47,49,51,54,63,65,67,68,70-72,76] COVID-19: coronavirus disease 2019

Figure 9. Funnel plot showing the association of anorexia with outcomes in COVID-19 hospitalized patients

COVID-19: coronavirus disease 2019

Figure 10. Forest plot showing the association of abdominal pain with outcomes in COVID-19 hospitalized patients

References: [45,47,49,60,63,70,74] COVID-19: coronavirus disease 2019