AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19

Abstract

Background & aims: Multiple gastrointestinal (GI) symptoms, including diarrhea, nausea/vomiting, and abdominal pain, as well as liver enzyme abnormalities, have been variably reported in patients with coronavirus disease 2019 (COVID-19). This document provides best practice statements and recommendations for consultative management based on a systematic review and meta-analysis of international data on GI and liver manifestations of COVID-19.

Methods: We performed a systematic literature search to identify published and unpublished studies using OVID Medline and preprint servers (medRxiv, LitCovid, and SSRN) up until April 5, 2020; major journal sites were monitored for US publications until April 19, 2020. We pooled the prevalence of diarrhea, nausea, vomiting, and abdominal pain, as well as liver function tests abnormalities, using a fixed-effect model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.

Results: We identified 118 studies and used a hierarchal study selection process to identify unique cohorts. We performed a meta-analysis of 47 studies including 10,890 unique patients. Pooled prevalence estimates of GI symptoms were as follows: diarrhea 7.7% (95% confidence interval [CI], 7.2%-8.2%), nausea/vomiting 7.8% (95% CI, 7.1%-8.5%), and abdominal pain 2.7% (95% CI, 2.0%-3.4%). Most studies reported on hospitalized patients. The pooled prevalence estimates of elevated liver abnormalities were as follows: aspartate transaminase 15.0% (95% CI, 13.6%-16.5%) and alanine transaminase 15.0% (95% CI, 13.6%-16.4%). When we compared studies from China to studies from other countries in subgroup analyses, diarrhea, nausea/vomiting, and liver abnormalities were more prevalent outside of China, with diarrhea reported in 18.3% (95% CI, 16.6%-20.1%). Isolated GI symptoms were reported rarely. We also summarized the Gl and liver adverse effects of the most commonly utilized medications for COVID-19.

Conclusions: GI symptoms are associated with COVID-19 in <10% of patients. In studies outside of China, estimates are higher. Further studies are needed with standardized GI symptoms questionnaires and liver function test checks on admission to better quantify and qualify the association of these symptoms with COVID-19. Based on findings from our meta-analysis, we provide several Best Practice Statements for the consultative management of COVID-19.

Keywords: COVID-19; Gastrointestinal and Liver Manifestations.

Figure 1

Forest plot of the prevalence of diarrhea in all patients.

Figure 2

Forest plot of the prevalence of nausea/vomiting in all patients.

Figure 3

Forest plot of the prevalence of abdominal pain in all patients.

Supplement Figure 1

PRISMA 2009 Flow Diagram

Supplementary Figure 2

The matrix used in the selection of the Chinese studies. The X-axis represents the studies. The Y axis represent the hospitals included in the study. The size of the bubble reflects the number of patients in the study. Two studies by Guan et al^, were not included in the plot as they included patients from more than 500 hospitals from 30 or more provinces without providing the names of the hospitals.

Supplementary Figure 3

Forest plot of the prevalence of diarrhea in all admitted patients regardless of the timing of diarrhea.

Supplementary Figure 4

Forest plot of the prevalence of diarrhea as one of the initial symptoms in all patients regardless of hospitalization status.

Supplementary Figure 5

Forest plot of the prevalence of diarrhea as one of the initial symptoms in all admitted patients.

Supplementary Figure 6

Forest plot of the prevalence of diarrhea in outpatients regardless of the timing of diarrhea.

Supplementary Figure 7

Forest plot of the prevalence of nausea/vomiting as one of the initial symptoms in all patients regardless of hospitalization status.

Supplementary Figure 8

Forest plot of the prevalence of abdominal pain as one of the initial symptoms in all patients regardless of hospitalization status.

Supplementary Figure 9

Forest plot of the prevalence of elevated AST.

Supplementary Figure 10

Forest plot of the prevalence of elevated ALT.

Supplementary Figure 11

Forest plot of the prevalence of elevated total bilirubin.