key: cord-336722-41eqt97y authors: Sehmi, P.; Cheruiyot, I. title: Presence of Live SARS-CoV-2 Virus in Feces of Coronavirus Disease 2019 (COVID-19) Patients: A Rapid Review date: 2020-06-29 journal: nan DOI: 10.1101/2020.06.27.20105429 sha: doc_id: 336722 cord_uid: 41eqt97y Coronavirus disease 2019 (COVID-19) is a rapidly escalating pandemic that has spread to many parts of the world. The disease has already affected over 6 million individuals, with over 400,000 fatalities. Recent studies have confirmed the presence of SARS-CoV-2 nucleic acids in feces of Coronavirus disease 2019 (COVID-19) patients using RT-PCR tests. It is however, still unclear as to whether or not live SARS-CoV-2 virus is actually present in feces of these patients. In this rapid review, we systematically analyzed literature to establish any evidence of live SARS-CoV-2 virus in fecal samples of COVID-19 patients. We identified 4 studies (one case report, 2 case series and 1 cohort study) where the SARS-CoV-2 was successfully isolated from fecal samples of COVID-19 patients using culture techniques. Therefore, there is some evidence COVID-19 could shed live SARS-CoV-2 virus via the gastro-intestinal tract. Larger studies are needed to corroborate these findings, as well as to determine its potential for disease transmission and infection, and possible implications for COVID-19 discharge and isolation policies. The coronavirus disease 2019 (COVID-19), which was first reported in Wuhan, China in December 2019, has achieved a pandemic status. As of 8 th June 2020, the disease had spread to over 180 countries and territories, with over 6,931,000 cases and >400,857 fatalities. 1 The disease is thought to be mainly spread through respiratory droplets and by fomites. 2 Whereas the disease primarily affects the respiratory system, a subset of COVID-19 patients presents with gastro-intestinal symptoms, 3, 4 raising concerns of potential alternative routes of viral shedding and disease transmission. The evidence supporting the potential of feco-oral transmission of COVID-19 has been predominantly based on the detection of viral ribonucleic acid (RNA) in feces using reverse transcriptase polymerase chain reaction (RT-PCR). [5] [6] [7] However, this technique does not usually distinguish infectious from non-infectious nucleic acid. 8 Therefore, detection of viral RNA in stool may not necessarily imply potential for transmission or infectivity. Stronger evidence of possibility of feco-oral transmission of COVID-19 may however be obtained by isolation and demonstration of live virus in stool. In this rapid review, we systematically analyze literature to establish if there is any evidence of the presence of live Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in feces of COVID-19 patients. This may have potential implications for management of COVID-19 patients, as well as discharge and isolation policies. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint A comprehensive and systematic search of literature from November 1, 2019 to June 6 th , 2020 was conducted on the Medline (PubMed interface) and China National Knowledge Infrastructure (CNKI) to identify studies eligible for inclusion. The electronic search was carried out using the strategy as follows: ((((SARS-CoV-2) OR (Live Virus)) AND (((Culture) OR (Isolation)) OR (Identification))) AND (((Feces) OR (Stool)) OR (Anal swabs)). No language restriction was applied. When the articles were published by the same study group and there was an overlap of the search period, only the most recent article was included to avoid duplication of data. The PubMed function "related articles" was used to extend the search. Also, we searched major infectious disease and general medicine journals reporting articles about COVID-19 infection to look for additional studies. We then performed hand-search of the bibliography of included studies, to detect other potentially eligible investigations. The search results were screened by title and abstract, with those of potential relevance evaluated by full text. Studies were deemed eligible for inclusion if they fulfilled the following criteria: (1) were case reports/case series/cohort studies, (2) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint For each study, the following information was extracted: the surname of the first author and the year of publication, the geographical region where the study was performed, study setting, sample size, number of patients tested for live virus in feces, number of patients with live virus in feces, methods of isolation & identification of live virus in feces. Due to the limited data available, pooling of data was not performed. Instead, the results were summarized in a "summary of findings table" and a narration provided. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint The initial search produced 278 potentially relevant articles. Following primary screening and removal of duplicates, 63 articles were assessed by full text for eligibility. Of these, 59 articles were excluded since they were review articles, commentaries, or other editorial materials, or did not contain data on isolation of live in stool specimens in COVID-19 patients. Therefore, 4 articles were included in the final synthesis ( figure 1 and table 1 ). All studies were from China. Essential characteristics of the included studies are provided in table 1. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint A total of 4 studies describing isolation of live SARS-CoV-2 virus in fecal samples of COVID-19 patients were included. [9] [10] [11] [12] The first study was by Zhang and colleagues 9 who successfully isolated live SARS-CoV-2 virus in the stool sample of a patient with severe COVID-19 using Vero cell culture and demonstrated it using electron microscopy. Using similar methods, Xiao et al., 10 were able to isolate and demonstrate the live virus in 2 out of 3 patients (67%) who had tested positive for SARS-CoV-2 RNA in stool samples tested by RT-PCR. The same authors in another report mentioned their unpublished findings on successful isolation of infectious SARS-CoV-2 from stool. 11 The fourth study was by Wang and colleagues 12 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint The findings from these four studies, though limited by the small sample sizes, confirm that live SARS-CoV-2 virus is present in fecal samples of COVID-19 patients, and therefore supports the hypothesis that COVID-19 could potentially be transmitted via the feco-oral route. These findings have important implications. First, isolation of live virus in feces implies that there is a potential risk of transmission of COVID-19 though aerosol generating procedures such as colonoscopy, endoscopy, laparoscopy, electrocautery. Appropriate cautionary measures such as use devices to filter released carbon dioxide during laparoscopy, as well as the use personal protective equipment when performing these procedures. Second, these findings affirm the need for routine testing of fecal samples of COVID-19 patients so as to enable the institution of appropriate public health policies to minimize potential feco-oral transmission of COVID-19. Our study was limited by the small number of the included studies, which were mainly case reports and case series. Larger high-quality studies are urgently needed to better characterize the magnitude of live SARS-CoV-2 viral shedding in feces, as well as its potential for disease transmission and infection, and possible implications for COVID-19 discharge and isolation policies. In conclusion, there's some evidence that COVID-19 patients could shed live SARS-CoV-2 virus via feces. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint Coronavirus disease 2019 (COVID-19) Situation Report -140. 2020. Accessed 9 th The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak COVID-19: gastrointestinal manifestations and potential fecal-oral transmission COVID-19: gastrointestinal symptoms and potential sources of 2019-nCoV transmission. Anaesthesiology intensive therapy The presence of SARS CoV 2 RNA in the feces of COVID 19 patients Detectable SARS CoV 2 viral RNA in feces of three children during recovery period of COVID 19 pneumonia Prolonged SARS Cov 2 RNA Detection in Anal/Rectal Swabs and Stool Specimens in COVID 19 Patients After Negative Conversion in Nasopharyngeal RT PCR Test SARS-CoV-2 shedding and infectivity. The Lancet International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity Isolation of 2019-nCoV from a stool specimen of a laboratory-confirmed case of the coronavirus disease 2019 (COVID-19). China CDC Weekly Infectious SARS-CoV-2 in feces of patient with severe COVID-19. Emerg Infect Dis Evidence for gastrointestinal infection of SARS-CoV-2 Detection of SARS-CoV-2 in different types of clinical specimens International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.27.20105429 doi: medRxiv preprint