Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis

Abstract

Background: Patients with COVID-19 usually manifest fever and respiratory symptoms. However, some patients also experience gastrointestinal (GI) symptoms such as diarrhea, vomiting and abdominal pain. In addition, SARS-CoV-2 RNA has been detected in feces of infected patients. Currently there is huge evolving research interest in this potentially lethal disease. We systematically reviewed and meta-analyzed the evidence suggesting involvement of the digestive system in COVID-19.

Methods: PubMed, Medline and Embase databases were searched up to 10 April 2020, using suitable keywords. Individual and pooled prevalence rates with 95% confidence intervals (CI) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity between studies was calculated employing the Cochran Q test and I² values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed.

Results: In adult COVID-19 patients, the prevalence rates (95%CI) for all GI symptoms, and separately for diarrhea, nausea/vomiting, and abdominal discomfort/pain were 9.8% (6.4-14.7), 10.4% (95%CI 7.7-13.9), 7.7% (95%CI 4.8-12.1), and 6.9% (95%CI 3.9-11.9) respectively. The prevalence rates for children were 9.6% (95%CI 6.3-14.3) for all symptoms, 9.6% (95%CI 6.3-14.3) for diarrhea, and 6.8% (95% CI 4.2-11) for nausea/vomiting. In 30.3% (95%CI 10.5-61.6) of the patients SARS-CoV-2 RNA was detected in feces.

Conclusions: A percentage of patients with COVID-19 will manifest symptoms from the digestive system. The GI tract may be a target organ and potential transmission route of SARS-CoV-2, with important implications for disease management and transmission.

Keywords: COVID-19; GI symptoms; SARS-CoV-2; abdominal pain; diarrhea; meta-analysis; nausea; stool SARS-CoV-2 RNA; systematic review; vomiting.

Figure 1

Flow diagram of the studies identified in this meta-analysis

Figure 2

Forest plot showing individual and pooled prevalence ratios and 95% confidence intervals (CIs)

Figure 3

Funnel plot of all studies included in the meta-analysis. There is evidence of publication bias (P=0.001 by regression test)

Figure 4

(A) Exclusion sensitivity plot showing the effect of exclusion of any study on the magnitude of the summary estimate. (B) Cumulative meta-analysis of included studies

Figure 5

Forest plots showing individual and pooled prevalence ratios and 95% confidence intervals for diarrhea (A), nausea/vomiting (B), and abdominal discomfort/pain (C)

Figure 6

(A) Forest plot showing individual and pooled prevalence ratios (95% confidence interval) of SARS-CoV-2 RNA detection in feces (B) Cartoon representation of the SARS-CoV-2 fecal route transmission. (C) Ribbon diagram depicting the SARS-CoV-2 attachment to ACE2 receptors (modified from ref. 66) (D) ACE2 small intestine immunolocalization (modified from ref. 12) ACE2, angiotensin-converting enzyme 2