COVID-19: Focus on the lungs but do not forget the gastrointestinal tract

Wiktor Smyk, Maciej K Janik, Piero Portincasa, Piotr Milkiewicz, Frank Lammert, Marcin Krawczyk, Wiktor Smyk, Maciej K Janik, Piero Portincasa, Piotr Milkiewicz, Frank Lammert, Marcin Krawczyk

Abstract

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.

Keywords: SARS-CoV-2; coronavirus; diarrhoea; faecal-oral transmission; gallbladder.

Conflict of interest statement

There are no conflicts of interest.

© 2020 Stichting European Society for Clinical Investigation Journal Foundation.

References

    1. Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model‐based analysis. Lancet Infect Dis. 2020;20(6):669‐677.
    1. Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019;17(3):181‐192.
    1. Mallapaty S. Coronavirus can infect cats ‐ dogs, not so much. Nature. 2020.
    1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses . The species severe acute respiratory syndrome‐related coronavirus: classifying 2019‐nCoV and naming it SARS‐CoV‐2. Nat Microbiol. 2020;5(4):536‐544.
    1. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14(8):523‐534.
    1. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID‐19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054‐1062.
    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;18(7):1636‐1637.
    1. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708‐1720.
    1. Deng Y, Liu W, Liu K, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020;133(11):1261‐1267.
    1. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):1‐9.
    1. Pan L, Mu MI, Yang P, et al. Clinical characteristics of COVID‐19 patients with digestive symptoms in Hubei, China: a descriptive, cross‐sectional, multicenter study. Am J Gastroenterol. 2020;115(5):766‐773.
    1. Lu X, Zhang L, Du H, et al. SARS‐CoV‐2 Infection in Children. N Engl J Med. 2020;382(17):1663‐1665.
    1. Wang D, Hu BO, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061.
    1. Liu K, Fang Y‐Y, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J. 2020;133(9):1025‐1031.
    1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507‐513.
    1. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID‐19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20(4):425‐434.
    1. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS‐CoV‐2. Gastroenterology. 2020;158:1831‐1833.
    1. Easom N, Moss P, Barlow G, et al. Sixty‐eight consecutive patients assessed for COVID‐19 infection: experience from a UK regional infectious disease unit. Influenza Other Respir Viruses. 2020;14(4):374‐379.
    1. Xu X‐W, Wu X‐X, Jiang X‐G, et al. 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. Chu J, Yang N, Wei Y, et al. Clinical characteristics of 54 medical staff with COVID‐19: a retrospective study in a single center in Wuhan, China. J Med Virol. 2020;92(7):807‐813.
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet. 2020;395(10223):497‐506.
    1. Song Y, Liu P, Shi XL, et al. SARS‐CoV‐2 induced diarrhoea as onset symptom in patient with COVID‐19. Gut. 2020;69(6):1143‐1144.
    1. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929‐936.
    1. Phan LT, Nguyen TV, Luong QC, et al. Importation and human‐to‐human transmission of a novel coronavirus in Vietnam. N Engl J Med. 2020;382(9):872‐874.
    1. Ping An HC, Jiang X, et al. Clinical features of 2019 novel coronavirus pneumonia presented gastrointestinal symptoms but without fever onset. Lancet. 2020.
    1. Bodini G, Demarzo MG, Casagrande E, et al. Concerns related to COVID‐19 pandemic among patients with inflammatory bowel disease and its influence on patient management. Eur J Clin Invest. 2020;50(5):e13233.
    1. Li W, Moore MJ, Vasilieva N, et al. Angiotensin‐converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450‐454.
    1. Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. J Mol Med. 2006;84(10):814‐820.
    1. Hoffmann M, Kleine‐Weber H, Schroeder S, et al. SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271‐280.e8.
    1. Tai W, He L, Zhang X, et al. Characterization of the receptor‐binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol. 2020;17(6):613‐620.
    1. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single‐cell RNA‐seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019‐nCoV infection. Front Med. 2020;14(2):185‐192.
    1. Lukassen S, Chua RL, Trefzer T, et al. SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. Embo J. 2020;39(10):e105114.
    1. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135‐140.
    1. Liang W, Feng Z, Rao S, et al. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020;69(6):1141‐1143.
    1. Sungnak W, Huang NI, Bécavin C, et al. SARS‐CoV‐2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26(5):681‐687.
    1. Gordon DE, Jang GM, Bouhaddou M, et al. A SARS‐CoV‐2 protein interaction map reveals targets for drug repurposing. Nature. 2020. 10.1038/s41586-020-2286-9
    1. Portincasa P, Moschetta A, Di Ciaula A, et al. Changes of gallbladder and gastric dynamics in patients with acute hepatitis A. Eur J Clin Invest. 2001;31(7):617‐622.
    1. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID‐2019. Nature. 2020;581(7809):465‐469.
    1. Wang W, Xu Y, Gao R, et al. Detection of SARS‐CoV‐2 in different types of clinical specimens. JAMA. 2020;323(18):1843‐1844.
    1. Zhang W, Du R‐H, Li B, et al. Molecular and serological investigation of 2019‐nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020;9(1):386‐389.
    1. Zhang J, Wang S, Xue Y. Fecal specimen diagnosis 2019 novel coronavirus‐infected pneumonia. J Med Virol. 2020;92(6):680‐682.
    1. Xu YI, Li X, Zhu B, et al. Characteristics of pediatric SARS‐CoV‐2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26(4):502‐505.
    1. Chen C, Gao G, Xu Y, et al. SARS‐CoV‐2‐positive sputum and feces after conversion of pharyngeal samples in patients With COVID‐19. Ann Intern Med. 2020;172(12):832‐834.
    1. Ong SWX, Tan YK, Chia PY, et al. Air, Surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) from a symptomatic patient. JAMA. 2020;323(16):1610.
    1. Repici A, Pace F, Gabbiadini R, et al. Endoscopy units and the coronavirus disease 2019 outbreak: a multicenter experience from Italy. Gastroenterology. 2020;S0016‐5085(20):30466‐2.
    1. Lin LU, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS‐CoV‐2 infection. Gut. 2020;69(6):997‐1001.
    1. Effenberger M, Grabherr F, Mayr L, et al. Faecal calprotectin indicates intestinal inflammation in COVID‐19. Gut. 2020.
    1. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID‐19). JAMA Cardiol. 2020.
    1. Shi S, Qin MU, Shen BO, et al. Association of cardiac injury with mortality in hospitalized patients with COVID‐19 in Wuhan, China. JAMA Cardiol. 2020.
    1. Yang X, Yu Y, Xu J, et al. 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;8(5):475‐481.
    1. Inciardi RM, Lupi L, Zaccone G, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID‐19). JAMA Cardiol. 2020.
    1. Ma K‐L, Liu Z‐H, Cao C‐F, et al. COVID‐19 myocarditis and severity factors: an adult cohort study. medRxiv. 2020.
    1. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID‐19 in the New York City Area. JAMA. 2020;323(20):2052‐2059.
    1. Recalcati S. Cutaneous manifestations in COVID‐19: a first perspective. J Eur Acad Dermatol Venereol. 2020;34(5):e212‐e213.
    1. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with coronavirus disease 2019 (COVID‐19) in Hubei Province, China. JAMA Ophthalmol. 2020;138(5):575.
    1. Giacomelli A, Pezzati L, Conti F, et al. Self‐reported olfactory and taste disorders in SARS‐CoV‐2 patients: a cross‐sectional study. Clin Infect Dis. 2020.
    1. COVID‐19 National Emergency Response Center, Epidemiology and Case Management Team, Korea Centers for Disease Control and Prevention . Early Epidemiological and . Early epidemiological and clinical characteristics of 28 cases of coronavirus disease in South Korea. Osong Public Health Res Perspect. 2020;11(1):8‐14.
    1. Chen T, Wu DI, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091.
    1. Redd WD, Zhou JC, Hathorn KE, et al. Prevalence and characteristics of gastrointestinal symptoms in patients with SARS‐CoV‐2 infection in the United States: a multicenter cohort study. Gastroenterology. 2020;S0016‐5085(20):30564‐3.
    1. Wu Y, Guo C, Tang L, et al. Prolonged presence of SARS‐CoV‐2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. 2020;5(5):434‐435.

Source: PubMed

3
Subscribe