SARS-CoV-2 and the role of orofecal transmission: a systematic review.

Background: Modes of transmission of SARS-CoV-2 are of key public health importance. SARS-CoV-2 has been detected in the feces of some COVID-19 patients, suggesting the possibility that the virus could, in addition to droplet and fomite transmission, be transmitted via the orofecal route.
Methods: This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. We conduct ongoing searches using WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings. Where necessary, authors are contacted for further details on the content of their articles.
Results: We include searches up until 20 December 2020. We included 110 relevant studies: 76 primary observational studies or reports, and 35 reviews (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Of the observational studies, 37 were done in China. A total of 48 studies (n=9,081 patients) reported single cases, case series or cohort data on individuals with COVID-19 diagnosis or their contacts and 46 (96%) detected binary RT-PCR with 535 out of 1358 samples positive for SARS-CoV-2 (average 39.4%). The results suggest a long duration of fecal shedding, often recorded after respiratory samples tested negative, and symptoms of gastrointestinal disease were reported in several studies. Twenty-nine studies reported finding SARS-CoV-2 RNA in wastewater, river water or toilet areas. Six studies attempted viral culture from COVID-19 patients' fecal samples: culture was successful in 3 of 6 studies, and one study demonstrated invasion of the virus into intestinal epithelial cells.
Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the gastrointestinal tract, including some data demonstrating viral culture in fecal samples. To fully assess these risks, quantitative data on infectious virus in these settings and infectious dose are needed.
Competing Interests: Competing interests: CH holds grant funding from the NIHR School of Primary Care Research, the NIHR BRC Oxford and the World Health Organization for a series of Living rapid review on the modes of transmission of SARs-CoV-2 reference WHO registration No2020/1077093. He has received expenses and fees for his media work. He receives expenses for teaching EBM and is also paid for his GP work in NHS out of hours (contract Oxford Health NHS Foundation Trust) and for appraising treatment recommendations in non-NHS settings. He is the Director of CEBM and is an NIHR Senior Investigator. TJ was in receipt of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews (2015-018). In 2014–2016, he was a member of three advisory boards for Boehringer Ingelheim. TJ was a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial on an influenza vaccine. TJ is occasionally interviewed by market research companies about phase I or II pharmaceutical products for which he receives fees (current). TJ was a member of three advisory boards for Boehringer Ingelheim (2014-16). TJ was a member of an independent data monitoring committee for a Sanofi Pasteur clinical trial on an influenza vaccine (2015-2017). TJ is a relator in a False Claims Act lawsuit on behalf of the United States that involves sales of Tamiflu for pandemic stockpiling. If resolved in the United States’ favor, he would be entitled to a percentage of the recovery. TJ is co-holder of a Laura and John Arnold Foundation grant for development of a RIAT support centre (2017-2020) and Jean Monnet Network Grant, 2017-2020 for The Jean Monnet Health Law and Policy Network. TJ is an unpaid collaborator to the project Beyond Transparency in Pharmaceutical Research and Regulation led by Dalhousie University and funded by the Canadian Institutes of Health Research (2018-2022). TJ consulted for Illumina LLC on next generation gene sequencing (2019-2020). TJ was the consultant scientific coordinator for the HTA Medical Technology programme of the Agenzia per i Serivizi Sanitari Nazionali (AGENAS) of the Italian MoH (2007-2019). TJ is Director Medical Affairs for BC Solutions, a market access company for medical devices in Europe. TJ is funded by NIHR UK and the World Health Organization (WHO) to update Cochrane review A122, “Physical Interventions to interrupt the spread of respiratory viruses”. TJ is funded by Oxford University to carry out a living review on the transmission epidemiology of COVID-19. Since 2020, TJ receives fees for articles published by The Spectator and other media outlets. TJ is part of a review group carrying out “Living rapid literature review on the modes of transmission of SARS-CoV-2 (WHO Registration 2020/1077093-0)”. He is a member of the WHO COVID-19 Infection Prevention and Control Research Working Group. JC holds grants from the Canadian Institutes for Health Research on acute and primary care preparedness for COVID-19 in Alberta, Canada and was the primary local Investigator for a Staphylococcus aureus vaccine study funded by Pfizer for which all funding was provided only to the University of Calgary. He also received support from the Centers for Disease Control and Prevention (CDC) to attend an Infection Control Think Tank Meeting. DE holds awards from the Canadian Institutes for Health Research and the Natural Sciences and Engineering Research Council of Canada to support poxvirus research as well as research relating to Covid-19 vaccine development and aerosol transmission. Funding from Alberta Health Services, Alberta Innovates, and the World Health Organization supports research concerning the mechanism of Covid-19 transmission and inactivation technologies. He also holds research contracts and consults with Tonix Pharmaceuticals in support of the development of poxvirus-based Covid-19 vaccines. IJO, EAS, JB, and AP have no interests to disclose.
(Copyright: © 2021 Heneghan CJ et al.)