Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis

Ka Shing Cheung, Ivan F N Hung, Pierre P Y Chan, K C Lung, Eugene Tso, Raymond Liu, Y Y Ng, Man Y Chu, Tom W H Chung, Anthony Raymond Tam, Cyril C Y Yip, Kit-Hang Leung, Agnes Yim-Fong Fung, Ricky R Zhang, Yansheng Lin, Ho Ming Cheng, Anna J X Zhang, Kelvin K W To, Kwok-H Chan, Kwok-Y Yuen, Wai K Leung, Ka Shing Cheung, Ivan F N Hung, Pierre P Y Chan, K C Lung, Eugene Tso, Raymond Liu, Y Y Ng, Man Y Chu, Tom W H Chung, Anthony Raymond Tam, Cyril C Y Yip, Kit-Hang Leung, Agnes Yim-Fong Fung, Ricky R Zhang, Yansheng Lin, Ho Ming Cheng, Anna J X Zhang, Kelvin K W To, Kwok-H Chan, Kwok-Y Yuen, Wai K Leung

Abstract

Background & aims: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong.

Methods: We collected data from the cohort of patients with COVID-19 in Hong Kong (N = 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model.

Results: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P = .02). The median fecal viral load was 5.1 log10 copies per milliliter in patients with diarrhea vs 3.9 log10 copies per milliliter in patients without diarrhea (P = .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3% of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1).

Conclusions: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.

Keywords: Fecal-to-Oral Transmission; PRISMA; SARS; Viral Persistence.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Study selection flow diagram. If all gastrointestinal symptoms were not reported and the number of events of any individual gastrointestinal symptom was >1, it was regarded as not available and was excluded from the meta-analysis of all gastrointestinal symptoms. However, the study was still included in the meta-analysis of individual gastrointestinal symptom if the proportion of patients with that symptom was reported.
Figure 2
Figure 2
Pooled prevalence of all gastrointestinal symptoms in patients with COVID-19 (all studies and according to geographical variation—China vs outside of China).
Figure 3
Figure 3
Summary estimates of the prevalence of individual and all gastrointestinal symptoms in patients with COVID-19. GI, gastrointestinal.
Figure 4
Figure 4
Pooled prevalence of all gastrointestinal symptoms according to the severity of COVID-19.
Figure 5
Figure 5
Timeline of the symptomatology and viral test results (respiratory and stool specimens) of 38 patients with COVID-19. A filled circle represents a positive result, and an empty circle represents a negative result. Gastrointestinal symptoms are color coded as shown (abdominal pain/discomfort, orange; vomiting, yellow; diarrhea, green). The details of 13 R–S+ patients are shown in case numbers 2, 5, 8, 10, 11, 14, 15, 18, 24, 26, 27, 28, and 29. Nasopharyngeal/oropharyngeal and stool samples were tested for viral RNA within 4–48 hours and 3–13 days after illness onset, respectively, in the study by Cai et al; the authors did not state the exact day from illness onset on which the respiratory and stool samples were tested for individual patients; in addition, all patients tested negative for 2 consecutive respiratory specimens, but the exact day on which the second consecutive respiratory specimen tested negative for viral RNA was not stated. The sample size of Young et al was 18 (3 had diarrhea on presentation); the authors did not state which particular patient who tested for stool viral RNA (n = 8) had diarrhea. The number of days (D) represents the days from symptom onset (fever, cough, dyspnea, sore throat, nasal congestion, rhinorrhea, sneezing, loss of appetite) and was not reported in the study by Zhang J et al; hence, the first day on which respiratory specimens were tested was regarded as day 1 in this graph.

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