Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

Ren Mao, Yun Qiu, Jin-Shen He, Jin-Yu Tan, Xue-Hua Li, Jie Liang, Jun Shen, Liang-Ru Zhu, Yan Chen, Marietta Iacucci, Siew C Ng, Subrata Ghosh, Min-Hu Chen, Ren Mao, Yun Qiu, Jin-Shen He, Jin-Yu Tan, Xue-Hua Li, Jie Liang, Jun Shen, Liang-Ru Zhu, Yan Chen, Marietta Iacucci, Siew C Ng, Subrata Ghosh, Min-Hu Chen

Abstract

Background: The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects of COVID-19 on the digestive system.

Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates.

Findings: We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I2=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I2=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I2=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio [OR] 7·10 [95% CI 1·93-26·07]; p=0·003; I2=0%) and abnormal liver function including increased ALT (1·89 [1·30-2·76]; p=0·0009; I2=10%) and increased AST (3·08 [2·14-4·42]; p<0·00001; I2=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I2=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 [95% CI 0·22-5·48]; p=0·030; I2=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 [95% CI 1·17-7·48]; p=0·02; I2=0%).

Interpretation: Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients.

Funding: None.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Study selection
Figure 2
Figure 2
Pooled estimate of the prevalence of gastrointestinal symptoms in patients with COVID-19
Figure 3
Figure 3
Pooled estimate of the prevalence of abnormal liver chemistry in patients with COVID-19
Figure 4
Figure 4
Prognosis of patients with COVID-19 Patients stratified by digestive system involvement. Odds ratio calculated with Mantel-Haenszel random-effects model.
Figure 5
Figure 5
Gastrointestinal symptoms according to COVID-19 severity (severe vs non-severe) Odds ratio calculated with Mantel-Haenszel random-effects model.
Figure 6
Figure 6
Liver chemistry according to COVID-19 severity (severe vs non-severe) Odds ratio calculated with Mantel-Haenszel random-effects model.

References

    1. WHO Coronavirus disease 2019 (COVID-19) Situation Report – 94.
    1. Guan WJ, Ni Z, Hu Y. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 doi: 10.1056/NEJMoa2002032. published online Feb 28.
    1. Xiao F, Tang M, Zheng X. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020 doi: 10.1053/j.gastro.2020.02.055. published online March 3.
    1. Qi F, Qian S, Zhang S. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Comm. 2020 doi: 10.1016/j.bbrc.2020.03.044. published online March 18.
    1. Holshue ML, DeBolt C, Lindquist S. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382:929–936.
    1. Wölfel R, Corman VM, Guggemos W. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 doi: 10.1038/s41586-020-2196-x. published online April 1.
    1. Yao X, Li T, He Z. A pathological report of three COVID-19 cases by minimally invasive autopsies. Chin J Pathol. 2020;49:E009.
    1. Xu Y, Li X, Zhu B. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26:502–505.
    1. Chang D, Lin M, Wei L. Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China. JAMA. 2020;323:1092–1093.
    1. Wang L, Gao Y, Lou L. The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China. Eur Respir J. 2020 doi: 10.1183/13993003.00398-2020. published online March 26.
    1. Jin X, Lian J, Hu J. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020 doi: 10.1136/gutjnl-2020-320926. published online March 24.
    1. Pan L, Mu M, Ren H. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol. 2020 doi: 10.14309/ajg.0000000000000620. published April 14.
    1. National Heart, Lung, and Blood Institute Study quality assessment tools.
    1. Wang Z, Yang B, Li Q. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa272. published online March 16.
    1. Huang C, Wang Y, Li X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Wu C, Chen X, Cai Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Int Med. 2020 doi: 10.1001/jamainternmed.2020.0994. published online March 13.
    1. Coronavirus disease (COVID-19) technical guidance: laboratory testing for 2019-nCoV in humans.
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Method. 2005;5:13.
    1. Egger M, Smith G, Schneider M. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634.
    1. Li Q, Guan X, Wu P. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207.
    1. Pan Y, Zhang D, Yang P. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis. 2020;20:411–412.
    1. Chen Q, Quan B, Li X. A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019. J Med Virol. 2020 doi: 10.1002/jmv.25755. published online March 12.
    1. Chan JF, Yuan S, Kok K. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395:514–523.
    1. Wang Z, Chen X, Lu Y. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Bioscience Trends. 2020;14:64–68.
    1. Zhang Z, Li X, Zhang W. Clinical features and treatment of 2019-nCov pneumonia patients in Wuhan: report of a couple cases. Virol Sin. 2020 doi: 10.1007/s12250-020-00203-8. published Feb 7.
    1. Lescure F, Bouadma L, Nguyen D. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30200-0. published online March 27.
    1. Luo C, Yao L, Zhang L. Possible transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a public bath center in Huai'an, Jiangsu Province, China. JAMA Netw Open. 2020;3
    1. Yu N, Li W, Kang Q. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30176-6. published online March 24.
    1. Zeng L, Xia S, Yuan W. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. 2020 doi: 10.1001/jamapediatrics.2020.0878. published online March 24.
    1. Arentz M, Yim E, Klaff L. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020 doi: 10.1001/jama.2020.4326. published online March 19.
    1. Young BE, Ong S, Kalimuddin S. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020;323:1488–1494.
    1. Chen N, Zhou M, Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
    1. Wang D, Hu B, Hu C. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 doi: 10.1001/jama.2020.1585. published online Feb 7.
    1. Song F, Shi N, Shan F. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology. 2020;295:210–217.
    1. Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
    1. Shi H, Han X, Jiang N. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20:425–434.
    1. Cai J, Xu J, Lin D. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa198. published online Feb 28.
    1. Wu J, Liu J, Zhao X. Clinical characteristics of imported cases of COVID-19 in Jiangsu Province: a multicenter descriptive study. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa199. published online Feb 29.
    1. Liu K, Fang Y, Deng Y. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J. 2020 doi: 10.1097/CM9.0000000000000744. published online Feb 7.
    1. Luo S, Zhang X, Xu H. Don't overlook digestive symptoms in patients with 2019 novel coronavirus disease (COVID-19) Clin Gastroenterol Hepatol. 2020 doi: 10.1016/j.cgh.2020.03.043. published online March 20.
    1. Ng M, Lee E, Yang J. Imaging profile of the COVID-19 infection: radiologic findings and literature review. Radiology: Cardiothoracic Imaging. 2020;2
    1. Yang W, Cao Q, Qin L. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J Infect. 2020;80:388–439.
    1. Lu X, Zhang L, Du H. SARS-CoV-2 infection in children. N Engl J Med. 2020;382:1663–1665.
    1. Xu X, Yu C, Qu J. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020;47:1275–1280.
    1. Xu X, Wu X, Jiang X. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606.
    1. Liu Y, Yang Y, Zhang C. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63:364–374.
    1. Zhou Z, Zhao N, Shu Y. Effect of gastrointestinal symptoms on patients infected with COVID-19. Gastroenterology. 2020 doi: 10.1053/j.gastro.2020.03.020. published online March 18.
    1. Zhang J, Dong X, Cao Y. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 doi: 10.1111/all.14238. published online Feb 19.
    1. Han C, Duan C, Zhang S. Digestive symptoms in COVID-19 patients with mild disease severity: clinical presentation, stool viral RNA testing, and outcomes. Am J Gastroenterol. 2020 doi: 10.14309/ajg.0000000000000664. published online April 15.
    1. Cao B, Wang Y, Wen D. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020 doi: 10.1056/NEJMoa2001282. published online March 18.
    1. Guo W, Li M, Dong Y. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 doi: 10.1002/dmrr.3319. published online March 31.
    1. Jin X, Lian J, Hu J. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020 doi: 10.1136/gutjnl-2020-320926. published online March 24.
    1. Du M, Cai G, Chen F. Multi-omics evaluation of gastrointestinal and other clinical characteristics of SARS-CoV-2 and COVID-19. Gastroenterology. 2020 doi: 10.1053/j.gastro.2020.03.045. published online March 28.
    1. Qiu H, Wu J, Hong L. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis. 2020 doi: 10.1016/S1473-3099(20)30198-5. published online March 25.
    1. Shi S, Qin M, Shen B. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020 doi: 10.1001/jamacardio.2020.0950. published online March 25.
    1. Wu P, Duan F, Luo C. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. 2020 doi: 10.1001/jamaophthalmol.2020.1291. published online March 31.
    1. Zheng M, Gao Y, Wang G. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 doi: 10.1038/s41423-020-0402-2. published online March 19.
    1. Song Y, Liu P, Shi X. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020 doi: 10.1136/gutjnl-2020-320891. published online March 5.
    1. Hosoda T, Sakamoto M, Shimizu H. SARS-CoV-2 enterocolitis with persisting to excrete the virus for about two weeks after recovering from diarrhea: a case report. Infect Control Hosp Epidemiol. 2020 doi: 10.1017/ice.2020.87. published online March 15.
    1. Ghinai I, McPherson TD, Hunter JC. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020;395:1137–1144.
    1. Wu Y, Guo C, Tang L. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. 2020;5:434–435.
    1. Carvalho A, Alqusairi R, Adams A. SARS-CoV-2 gastrointestinal infection causing hemorrhagic colitis: implications for detection and transmission of COVID-19 disease. Am J Gastroenterol. 2020 doi: 10.14309/ajg.0000000000000667. published online April 17.
    1. Chen C, Gao G, Xu Y. SARS-CoV-2-positive sputum and feces after conversion of pharyngeal samples in patients with COVID-19. Ann Int Med. 2020 doi: 10.7326/M20-0991. published online March 30.
    1. Liu Q, Wang R, Qu G. Macroscopic autopsy findings in a patient with COVID-19. J Forensic Med. 2020;36:1–3. (in Chinese).
    1. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5:428–430.
    1. Chai X, Hu L, Zhang Y. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020 doi: 10.1101/2020.02.03.931766.
    1. Xu Z, Shi L, Wang Y. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420–422.
    1. Fan Z, Chen L, Li J. Clinical features of COVID-19 related liver damage. medRxiv. 2020 doi: 10.1101/2020.02.26.20026971.
    1. Yang X, Yu Y, Xu J. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 doi: 10.1016/S2213-2600(20)30079-5. published Feb 24.
    1. Huang Y, Yang R, Xu Y. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv. 2020 doi: 10.1101/2020.02.27.20029009. (preprint).
    1. Zhang B, Zhou X, Qiu Y. Clinical characteristics of 82 death cases with COVID-19. medRxiv. 2020 doi: 10.1101/2020.02.26.20028191. (preprint).
    1. van Doremalen N, Bushmaker T, Morris DH. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382:1564–1567.
    1. Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol. 2020;5:335–337.

Source: PubMed

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