Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis

Abstract

Background: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored.

Objectives: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course.

Methods: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome.

Results: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3).

Conclusions: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

Keywords: 2019-nCoV; COVID-19; Coronavirus; Novel coronavirus; SARS-CoV-2; nCoV-2019.

Fig. 1

PRISMA flow diagram depicting the flow of information through different phases of the systematic review. PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Fig. 2

Forest plot showing pooled odds ratio for patients with higher age (≥ 60 years) developing severe clinical course

Fig. 3

Forest plot showing pooled odds ratio for patients having any comorbidity developing severe clinical course

Fig. 4

Forest plot showing pooled odds ratio for patients with chronic liver disease developing severe clinical course

Fig. 5

Forest plot showing pooled odds ratio of diarrhea being associated with severe clinical course

Fig. 6

Forest plot showing pooled odds ratio of higher than normal values of aspartate aminotransferase being associated with severe clinical course

Fig. 7

Forest plot showing pooled odds ratio of higher than normal values of alanine transaminase being associated with severe clinical course

Fig. 8

Forest plot showing pooled odds ratio of higher than normal values of serum bilirubin being associated with severe clinical course

Fig. 9

Forest plot showing pooled odds ratio of lower than normal values of serum albumin being associated with severe clinical course

Fig. 10

Forest plot showing pooled odds ratio of higher than normal values of prothrombin time being associated with severe clinical course