Public health might be endangered by possible prolonged discharge of SARS-CoV-2 in stool
Authors: Yu He, Zhengli Wang, Fang Li, Yuan Shi
Journal: Journal of Infection (2020)

•The published data, which showed the COVID-19 patients with low digestive.•manifestation, might be misleading. Case with negative URT test showed positive in.•rectal scarab which challenge the isolation protocol.•As fomite transmission caused clusters of infection of SARS, adequate disinfection.•operations should be adopted in SARS-CoV-2 outbreak. According to a recent report, since December 8 2019, a novel identified coronavirus, SARS-CoV-2(previously named as 2019-nCOV) is causing outbreak of pneumonia in Wuhan, China and become the major concern throughout the world [[1]Tang J.W. Tambyah P.A. Hui D.S. Emergence of a novel coronavirus causing respiratory illness from Wuhan, China.J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.01.014Abstract Full Text Full Text PDF Scopus (113) Google Scholar]. The World Health Organization has recently announced this disease to constitute a public health emergency of international concern and then named this disease as Corona Virus Disease 2019 (COVID-19). By the 28 Feb, 2020, more than 80,000 confirmed cases including over 2500 death cases were officially announced. Till now, the infection control and surveillance focus on respiratory system. The ignorance of SARS-CoV-2 in digestive system may cause troubles in the disease control. Gastrointestinal symptoms seem to be uncommon in patients with COVID-19 when compared with Severe Acute Respiratory Syndrome (SARS) (Table 1) [[2]Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (32456) Google Scholar,[3]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.The Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14212) Google Scholar. However, they should not be ignored as the increasing rate of diarrhea occurs in confirmed COVID-19 patients according to a recent report that 14 of 138 confirmed patients had diarrhea [[4]Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; https://doi.org/10.1001/jama.2020.1585Crossref Scopus (16038) Google Scholar]. Those early reports may not represent actual rate of gastrointestinal symptoms caused by SARS-CoV-2, because in early stages of the outbreak, the limited resources for detection were only provided to those patients with severe symptoms like respiratory distress syndrome. About 27 percent of SARS patients have diarrhea and since full-length genome sequences identified that SARS-CoV-2 is 79.5% identical to SARS-CoV and share the same receptor angiotensin-converting enzyme 2 (ACE2), it is estimated that rate of gastrointestinal symptoms would be higher in patients with COVID-19 [[5]Donnelly C.A. Ghani A.C. Leung G.M. et al.Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.The Lancet. 2003; 361: 1761-1766Abstract Full Text Full Text PDF PubMed Scopus (783) Google Scholar].Table 1Presenting clinical features in COVID-19 series and SARS.ItemsCOVID-19 [2]Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.The Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (32456) Google ScholarCOVID-19 [3]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.The Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14212) Google ScholarCOVID-19 [4]Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; https://doi.org/10.1001/jama.2020.1585Crossref Scopus (16038) Google ScholarSARS [6]Zhang H, Kang Z, Gong H, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. BioRxiv 2020. doi:10.1101/2020.01.30.927806.Google ScholarJournalLancetLancetJAMALancetCases41991381425Published data2020/1/242020/1/292020/2/72003/3/24Fever (%)988398.694Cough (%)76828250.4Shortness of breath (%)553131.230.6Sputum production (%)28NA26.827.8Diarrhea (%)3210.127Death (%)15114.3< 60 years old: 13•2%.>60 years old: 43.3%COVID-19: Corona Virus Disease 2019; SARS: Severe Acute Respiratory Syndrome. Open table in a new tab COVID-19: Corona Virus Disease 2019; SARS: Severe Acute Respiratory Syndrome. One possible route for the movement of SARS-CoV-2 into digestive system may be "trachea-esophagus-ileum-colon" as single-cell transcriptom analysis showed ACE2, the entry receptor for SARS-CoV-2, highly expressed in lung AT2 cells, esophagus upper and stratified epithelial cells and enterocytes from ileum and colon [[6]Zhang H, Kang Z, Gong H, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. BioRxiv 2020. doi:10.1101/2020.01.30.927806.Google Scholar]. The evidence for this route is that all of the specimens including pharyngeal swab, esophageal biopsy, gastric mucosa, rectal mucosa, duodenal mucosa and stool tested positive to SARS-CoV-2 in two cases [[7]Guan W.-j., Ni Z.-y., Hu Y., et al. Clinical Characteristics of Coronavirus Disease 2019 in China. NEJM 2020. doi:10.1056/NEJMoa2002032.Google Scholar]. Another route may be bloodstream infection since SARS-CoV-2 was directly detected in bleeding site in one case [[7]Guan W.-j., Ni Z.-y., Hu Y., et al. Clinical Characteristics of Coronavirus Disease 2019 in China. NEJM 2020. doi:10.1056/NEJMoa2002032.Google Scholar]. In addition, expression of ACE2 in endothelial cells and macrophages, as well as the detection of SARS-CoV in plasma and blood lymphocytes also support the possibility of bloodstream infection of SARS-CoV-2 [[8]Zhao Y, Zhao Z, Wang Y, et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv 2020. doi:10.1101/2020.01.26.91998.Google Scholar,[9]Wang, H. Detection and monitoring of SARS coronavirus in the plasma and peripheral blood lymphocytes of patients with severe acute respiratory syndrome. Clin. Chem. 2004;50(7) 1237–40.Google Scholar. The discharge guideline depending on respiratory tract test also meets challenge. In cases, SARS-CoV-2 infected infant initially behaved as vomiting, diarrhea or feeding intolerance [[15]Wang J. Wang D. Chen G.C. et al.SARS-CoV-2 infection with gastrointestinal symptoms as the first manifestation in a neonate.Zhongguo Dang Dai Er Ke Za Zhi. 2020; 22: 211-214PubMed Google Scholar]. Interestingly, while the virus test of nasopharyngeal swab switched from positive to negative after treatment, the rectal swab specimens still tested positive [[10]Lingkong Z. Xuwei T. Wenhao Y. Jin W. Xin L. Zhisheng L. First case of neonate infected with novel coronavirus pneumonia in China.Chin J Pediatr. 2020; 58 (E009-E)Google Scholar]. These cases remind the clinicians that the rectal swab may be equally important to the pharyngeal swab even the patient is asymptomatic which challenge the latest published guideline provided by National Health Commission of China that two successive negative of the respiratory tract tests are regarded as the standard for discharge and termination of compulsory isolation for COVID-19 patients [[11]New coronavirus pneumonia prevention and control program 5th ed. 2020http://www.nhc.gov.cn/jkj/s3577/202002/a5d6f7b8c48c451c87dba14889b30147.shtmlDate accessed: February 28, 2020Google Scholar]. A famous well-described clusters of infection of SARS in Amoy Gardens, Hong Kong drew the attention of health official on fomite transmission because two thirds of the confirmed SARS patients in this Amoy Gardens had diarrhea [[12]Lee S.H. The SARS epidemic in Hong Kong.J Epidemiol Commun Health. 2003; 57: 652-654Crossref PubMed Scopus (56) Google Scholar]. As findings showed that patients with SARS could discharge SARS-CoV in their stool up to 73 days after symptom onset, the stools with the virus became the resource of contamination of airdrops and a variety of environmental surfaces, which may contribute to the clusters of infection [[13]Leung W.K., To K.-f., Chan P.K.S., et al. Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection. Gastroenterology 2003;125(4) 1011–7.Google Scholar]. Similarly, evidence showed that SARS-CoV-2 were identified in 4 stool specimens (4 out of 62), so fomite transmission should not be ignored in the transmission of SARS-CoV-2 since the virus may move from respiratory tract in to gastrointestinal tract the recovered patients may discharge the stool with virus for a long time [[9]Wang, H. Detection and monitoring of SARS coronavirus in the plasma and peripheral blood lymphocytes of patients with severe acute respiratory syndrome. Clin. Chem. 2004;50(7) 1237–40.Google Scholar]. According to a recent published report by CDC of China, the community acquired infections are becoming the predominant route in transmission [[14]Team TNCPEREThe epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.Chin J Epidemiol. 2020; : 145-151Google Scholar]. Based on these cases and the lessons from SARS, we recommend 1) the attentions should be drawn in digestive symptoms and stool or rectal scwrab tests for patients with suspicion or confirmed SARS-CoV-2 infection, 2) preventive education and publicity on hands washing and bathroom infection, 3) compulsory isolation till scwrab tests switch to negative, 4) surveillance and adequate disinfection in latrines in areas with severSARS-CoV-2 infection to avoid fomite transmission. The authors declare no conflicts of interest.