key: cord-0687925-wp05tv3m authors: Liu, Jing; Cui, Min; Yang, Tao; Yao, Ping title: Correlation between gastrointestinal symptoms and disease severity in patients with COVID-19: a systematic review and meta-analysis date: 2020-07-13 journal: BMJ Open Gastroenterol DOI: 10.1136/bmjgast-2020-000437 sha: 6f4bc248c4340e233d12c833360192cecdec507b doc_id: 687925 cord_uid: wp05tv3m OBJECTIVE: To study the correlation between gastrointestinal (GI) symptoms and disease severity in patients with COVID-19. DESIGN: We searched six databases including three Chinese and three English databases for all the published articles on COVID-19. Studies were screened according to inclusion and exclusion criteria. The relevant data were extracted and all the statistical analyses were performed using Revman5.3. RESULT: In a meta-analysis of 9 studies, comprising 3022 patients, 479 patients (13.7%, 95% CI 0.125 to 0.149) had severe disease and 624 patients (14.7%, 95% CI 0.136 to 0.159) had GI symptoms. Of 624 patients with GI symptoms, 118 patients had severe disease (20.5%, 95% CI 0.133 to 0.276) and of 2397 cases without GI symptoms, 361 patients had severe disease (18.2%, 95% CI 0.129 to 0.235). Comparing disease severity of patients with and without GI symptoms, the results indicated: I²=62%, OR=1.21, 95% CI 0.94 to 1.56, p=0.13; there was no statistically significant difference between the two groups. The funnel plot was symmetrical with no publication bias. CONCLUSION: Current results are not sufficient to demonstrate a significant correlation between GI symptoms and disease severity in patients with COVID-19. Since December 2019, novel coronavirus (SARS-CoV-2)-infected disease (COVID- 19) has gradually swept the world. Morbidity and mortality are increasing due to the high infectivity of the disease worldwide. By 20 April 2020, a total of 2 291 281 infections and 160 044 deaths had been confirmed in 211 countries and regions, with a case fatality rate of 7%, and the number of infections and deaths was dramatically rising daily. SARS-CoV-2 belongs to the same coronavirus family as SARS-CoV and MERS-CoV. 1 But its transmission speed is higher than the other two, and transmission channels are more diversified, including respiratory and digestive tract. 2 3 Earlier studies indicated that the clinical symptoms of COVID-19 vary and not all appear as respiratory symptoms. In some cases, the main symptoms are gastrointestinal (GI) symptoms such as abdominal pain, diarrhoea, nausea and vomiting. 4 Moreover, there are many patients of severe disease with GI symptoms. 5 Hence, it is essential to explore the correlation between digestive symptoms and disease severity, so as to pre-estimate the disease severity and give appropriate early special care and treatment. What are the new findings? ► Gastrointestinal (GI) symptoms accounted for a certain proportion in patients with COVID-19, though fever and cough still were the main symptoms. ► There was no statistically significant difference in severity of COVID-19 between patients with and without GI symptoms, but the proportion of severe disease in patients with GI symptoms was higher than in patients without GI symptoms. How might it impact on clinical practice in the foreseeable future? China Science and Technology Journal Database). The keywords are as follows: 'COVID-19', 'gastrointestinal symptoms' and so on. Inclusive criteria: (1) research types : cross-sectional studies, case control studies and case series; (2) research subjects: patients with confirmed COVID-19; (3) data items: including demographic characteristics (age and gender), clinical characteristics (fever, dry cough, fatigue, nausea and vomiting, abdominal pain and diarrhoea) and comorbidities (hypertension and diabetes). Exclusive criteria: (1) the type of study is case report, review and so on; (2) repeated research; (3) lack of the above case data; (4) animal experiments. A total of 2324 articles were retrieved. Browse the titles and abstracts, remove duplicate references, leaving 57 studies. After reading the full text, 48 articles were removed. Finally, a total of 9 studies 5-13 (including 8 English articles and 1 Chinese literature) and 3022 patients were included (figure 1). The Newcastle-Ottawa Scale (NOS) scoring system scored an average of 7.7 (6) (7) (8) , indicating that the quality of selected studies was relatively high. Meta-analysis was performed using Revman5.3. I² statistics are calculated to measure the proportion of total variation in study estimates attributed to heterogeneity. The combined OR and 95% CI (p<0.05) were calculated Figure 3 The incidence of severe type. Open access for heterogeneity. The forest plot and funnel plot were developed to assess heterogeneity and publication bias. The 7) . The funnel plot was symmetrical with no publication bias( figure 8) . The outcome showed that there was no significant correlation between GI symptoms and disease severity in patients with COVID-19. In this study, fever (85.9%) and respiratory symptoms (60.5%) were still the main manifestations in patients with COVID-19, but GI symptoms (14.7%), such as nausea, 18 Liang et al 19 reported that due to the high ACE2 expression in proximal and distal enterocytes, intestine may be vulnerable to SARS-CoV-2 infection. GI symptoms, such as vomiting and diarrhoea, lead to the interruption of intestinal flora and electrolyte disturbance such as low potassium and imbalance of water and sodium. This is likely to worsen the patients' condition. However, the result of this meta-analysis showed that there was no statistical correlation between the presence of GI symptoms and the severity of COVID-19. Although there was no statistical significance, the result that the proportion of severe disease in patients with GI symptoms (20.5%) was higher than that in patients without GI symptoms (18.2%) was evident. This study also has some limitations: (1) the languages of retrieval literature are limited to Chinese and English and all the articles are limited to published literature and (2) GI symptoms may be under-reported in some studies, which may cause a lower pooled prevalence rate. Despite the limitations, this meta-analysis overcomes the shortcomings of small sample size and regional restrictions. The heterogeneity and publication bias among the studies are moderate and the results are relatively objective. In summary, current findings are not sufficient to demonstrate a significant correlation between GI symptoms and disease severity in patients with COVID-19. Large multicentric prospective studies are required to confirm our findings. 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