Gastrointestinal and Hepatic Manifestations of COVID-19 in Children: A Systematic Review and Meta-analysis

Abstract

Background. Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction.Objective. To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness. Methods. A systematic literature search was done from inception until January 4, 2021 using PubMed, CochraneLibrary, Google Scholar and prepublication repositories with no language restrictions. Studies that reported thedemographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14. Results. We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies. The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without. Conclusion. One-third of children with COVID-19 exhibit at least one GI symptom and more likely presentin those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepaticmanifestations were higher among children with MIS-C.