Gastrointestinal and liver involvement in patients with COVID-19

We read with interest the systematic review and meta-analysis by Ren Mao and colleagues¹ that aimed to quantify the effect of COVID-19 on the digestive system. The study concluded that digestive symptoms and liver injury are common among patients with COVID-19 and that patients with severe disease have a higher risk of developing gastrointestinal symptoms and liver injury than do patients with non-severe COVID-19. However, we would like to highlight a couple of potential limitations to the method.

First, although the authors used a rigorous and comprehensive search strategy and selection process for identification of relevant articles, they do not appear to have assessed whether some patients had been included in more than one study. This finding is a common pitfall during the current global health emergency, possibly because of the rush to communicate clinical findings. The possibility of reporting the same patients in multiple reports has raised concerns,² because it could compromise the internal validity of meta-analyses aiming to summarise the body of evidence, and could result in substantial underestimation or overestimation of the results. This consideration is particularly important during major public health emergencies, in which there is an imperative need for reliable information to manage patients and to allow proper allocation of health-care resources in a cost-effective manner.

Our second concern regards the analysis that aimed to determine whether severe COVID-19 is associated with gastrointestinal symptoms and liver injury—namely, the definition of severity. There is a substantial heterogeneity in the definitions used for severe COVID-19, such as those from WHO interim guidelines for COVID-19,³ the community-acquired pneumonia guidelines from the American Thoracic Society,⁴ or the Chinese novel coronavirus pneumonia prevention and control programme.⁵ Additionally, some primary studies have used their own definitions for severity, whereas others do not provide their definition. We think that a sensitivity analysis including only studies with similar severity definitions might be appropriate.