Pooled Prevalence of Diarrhea Among COVID-19 Patients.

Dear Editor:

We read the article by D’Amico et al discussing the pathogenesis, epidemiology, prevention, and management of diarrhea among patients with coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We agree on the importance of such reviews, primarily targeted to gastroenterologists. Nevertheless, we would like to discuss additional implications and analyses presented by D’Amico et al regarding the prevalence of diarrhea derived from available published studies, and its comparison with SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV) infections.

D’Amico et al analyzed in the results from 20 studies in Table 1 in their article, with a pooled prevalence of 10.4%, although no information on the meta-analysis model was provided. We used that data, and additionally included 11 novel studies, published through May 3, 2020, also assessing the frequency of diarrhea among COVID-19 patients. With a total of 3335 patients from 31 studies, we used random-effects and fixed-effects models to determine the pooled prevalence. We used the Open Meta-Analyst software (Providence, RI). For the random-effects model, we found that 13.8% of patients presented with diarrhea (95% CI, 10.6%–17.0%), and for the fixed-effects model, 6.1% presented with diarrhea (95% CI, 5.4%–6.9%) (Figure 1 ). In the case of SARS-CoV and MERS-CoV, D’Amico et al did not provide pooled prevalences for comparisons with SARS-CoV-2. Then, we used the data D’Amico et al presented about these previous coronaviruses regarding diarrhea and we added 2 studies on SARS-CoV. Combining the data from 735 patients with SARS-CoV, the pooled prevalence yielded 12.4% (95 CI, 4.8%–20.0%) in the random-effects model, and 2.3% (95% CI, 1.3%–3.3%) in the fixed-effects model (Figure 1). In the case of MERS-CoV, this was 23.1% (95% CI, 10.7%–35.4%) and 17.5% (95% CI, 13.1%–21.9%), respectively (Figure 1).

Figure 1

Random-effects and fixed-effects model for the pooled prevalence of diarrhea among COVID-19 patients.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21

In addition to the cohort, cross-sectional, and case series studies, D’Amico et al also included 3 case reports. We also looked at those and found 6 more case reports. Most of them are from China (5), followed by Japan (2), the United States (1), and Lebanon (1), with a median diarrhea duration of 3 days, with the number of evacuations ranging from 2 to 6 per day.2, 3, 4, 5, 6, 7

In a previous meta-analysis, we found that diarrhea was reported among 6.1% (95% CI, 2.4%–9.7%) of patients with COVID-19 (6 studies, 457 patients), which was the same prevalence obtained now with 31 studies and 3335 patients by the fixed-effects model in the current analysis (Figure 1). Although this would be considered a low prevalence, the COVID-19 pandemic has affected 10.49 million people worldwide (as of July 1, 2020), translating into between 566,897 and 724,368 diarrhea-associated cases (based on 95% CIs for pooled prevalence).

Because SARS-CoV-2 directly or indirectly may affect the enteric mucosa, diarrhea and other gastrointestinal findings should raise clinical suspicion for COVID-19, with or without the presence of fever, cough, and other respiratory and nonrespiratory manifestations.

Finally, as D’Amico et al mentioned, fecal–oral transmission may be an additional source of transmission that deserves more research and subsequent preventive interventions.