Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel
Authors: Gianluca Ianiro, Benjamin H Mullish, Colleen R Kelly, Harry Sokol, Zain Kassam, Siew C Ng, Monika Fischer, Jessica R Allegretti, Luca Masucci, Faming Zhang, Josbert Keller, Maurizio Sanguinetti, Samuel P Costello, Herbert Tilg, Antonio Gasbarrini, Giovanni Cammarota
Journal: The Lancet. Gastroenterology & hepatology (2020)

As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread from China to other countries, governments and the medical community are taking steps to prevent transmission, from common sense recommendations to radical quarantine measures.1Xiao Y Torok ME Taking the right measures to control COVID-19.Lancet Infect Dis. 2020; (published online March 5.)https://doi.org/10.1016/S1473-3099(20)30152-3Summary Full Text Full Text PDF PubMed Scopus (220) Google Scholar In that context, timely recommendations concerning the screening of donors of human cells, tissues, or cellular or tissue-based products have been released, as the potential for transmission of COVID-19 through transplant is not yet known. Several institutions have recommended interim precautions to screen new donors. The US Food and Drug Administration has suggested considering a donor's history of travel to areas of outbreak, cohabitation with infected individuals, or diagnosis or suspicion of COVID-19 within the 28 days before recovery of donor tissue.2US Food and Drug AdministrationImportant Information for human cell, tissue, or cellular or tissue-based product (HCT/P) establishments regarding the 2019 novel coronavirus outbreak.https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-human-cell-tissue-or-cellular-or-tissue-based-product-hctp-establishmentsDate: 14 Feb, 2020Date accessed: March 6, 2020Google Scholar Similar measures have been taken by the Global Alliance of Eye Bank Associations and by the Joint United Kingdom Blood Transfusion Services Professional Advisory Committee to rule out potential donors.3Global Alliance of Eye Bank AssociationsALERT: Coronavirus (COVID-2019) and ocular tissue donation.https://www.gaeba.org/2020/alert-coronavirus-2019-ncov-and-ocular-tissue-donation/Date: Feb 3, 2020Date accessed: March 6, 2020Google Scholar, 4Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory CommitteeCoronavirus infection.https://www.transfusionguidelines.org/dsg/wb/guidelines/coronavirus-infectionDate: 2020Date accessed: March 6, 2020Google Scholar The European Society for Blood and Marrow Transplantation has recommended excluding potential donors who have been diagnosed with COVID-19, and waiting at least 21 days before donation in those with a history of high-risk travel or contact.5European Society for Blood and Marrow TransplantationCoronavirus disease COVID-19: updated EBMT recommendations.https://www.ebmt.org/ebmt/news/ebmt-recommendation-coronavirus-disease-covid-19https://www.ebmt.org/ebmt/news/ebmt-recommendation-coronavirus-disease-covid-19https://www.ebmt.org/ebmt/news/ebmt-recommendation-coronavirus-disease-covid-19https://www.ebmt.org/ebmt/news/ebmt-recommendation-coronavirus-disease-covid-19Date: 2020Date accessed: March 6, 2020Google Scholar In Italy, where the COVID-19 outbreak is spreading rapidly, the national transplant centre has taken stronger measures and has recommended testing all potential tissue and stem-cell living donors, as well as dead donors, through real-time RT-PCR assays of nasopharyngeal swab samples (or bronchoalveolar lavage in deceased individuals).6Ministero Della SaluteOggetto: aggiornamento delle misure di prevenzione della trasmissione dell'infezione da nuovo coronavirus (SARS-CoV-2) in Italia attraverso il trapianto di organi, tessuti e cellule.http://www.trapianti.salute.gov.it/imgs/C_17_cntAvvisi_231_0_file.pdfDate: March 3, 2020Date accessed: March 6, 2020Google Scholar Faecal microbiota transplantation is a novel treatment that has rapidly earned a major role in the management of recurrent Clostridioides difficile infection because of its clear advantages over antibiotics.7Ianiro G Murri R Sciumè GD et al.Incidence of bloodstream infections, length of hospital stay, and survival in patients with recurrent Clostridioides difficile infection treated with fecal microbiota transplantation or antibiotics a prospective cohort study.Ann Intern Med. 2019; 171: 695-702Crossref Scopus (77) Google Scholar It is becoming increasingly more widespread and standardised around the world. Last year, an international expert panel, including several authors of this Comment, released recommendations on how to screen faecal microbiota transplant donors, including a medical history and blood and stool examinations.8Cammarota G Ianiro G Kelly CR et al.International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.Gut. 2019; 68: 2111-2121Crossref PubMed Scopus (273) Google Scholar Given the global COVID-19 outbreak, we, as an international group of experts in faecal microbiota transplantation and stool banking, believe that recommendations to update (at least temporarily) the screening of stool donors are urgently needed, as the risk of transmitting SARS-CoV-2 by faecal microbiota transplantation might be higher than that in other tissue transplants. Evidence has shown that the SARS-CoV-2 can be found in faeces, and that stool samples can remain positive for the virus even when it is no longer detectable in the respiratory tract, suggesting the possibility of a faecal–oral route of transmission.9Xiao F Tang M Zheng X Liu Y Li X Shan H Evidence for gastrointestinal infection of SARS-CoV-2.Gastroenterology. 2020; (published online March 3.)DOI:10.1053/j.gastro.2020.02.055Summary Full Text Full Text PDF Scopus (2008) Google Scholar This concept is supported by the presence of gastrointestinal symptoms in some patients affected by COVID-19.10Wang D Hu B Hu C et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; (published online Feb 7.)DOI:10.1001/jama.2020.1585Crossref Scopus (16201) Google Scholar Another relevant issue is that faecal microbiota transplantation is not classified in the same way worldwide, as some countries regulate these transplants as a drug (eg, the USA, the UK, and France), some as a tissue (eg, Italy), and others do not provide specific regulation (eg, Australia).8Cammarota G Ianiro G Kelly CR et al.International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.Gut. 2019; 68: 2111-2121Crossref PubMed Scopus (273) Google Scholar This discrepancy results in a confusing scenario, in which some countries will apply rules for human cells, tissues, or cellular or tissue-based products, and others will not, potentially contributing to the spread of the infection. A more alarming issue is represented by the uncontrolled practice of homemade faecal microbiota transplantation, which is widespread among patients who want to try this treatment for indications outside of clinical guidelines or clinical trials.11Ekekezie C Perler BK Wexler A Duff C Lillis CJ Kelly CR Understanding the scope of do-it-yourself fecal microbiota transplant.Am J Gastroenterol. 2020; (published online Jan 10.)DOI:10.14309/ajg.0000000000000499Crossref PubMed Scopus (24) Google Scholar To prevent SARS-CoV-2 transmission, we propose additions to the current donor screening measures. In all countries, before each donation, physicians should screen for two main items: the presence of typical COVID-19 symptoms (including fever, fatigue, dry cough, myalgia, dyspnoea, and headache) within the previous 30 days; and the donor's history of travel to regions known to be affected by COVID-19 or close contact with individuals with proven or suspected infection, within the previous 30 days. If either of these items is positive, the potential donor should either be rejected or tested with RT-PCR assay for SARS-CoV-2. In endemic countries, the RT-PCR assay should be considered in all donors, even if they are asymptomatic or do not have a history of high-risk travel or contact. Alternatively, donor stools should be stored and quarantined for 30 days before use, and released only if the donor has not developed symptoms. Finally, stool banks should retrospectively check the health status of the donor before using frozen faeces, according to local epidemiology, to avoid further potential spreading of SARS-CoV-2. These suggestions should be tailored to local health-care organisations, and should be updated accordingly as further insight into COVID-19 and SARS-CoV-2 is gained. This online publication has been corrected. The corrected version first appeared at thelancet.com/gastrohep on May 14, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com/gastrohep on May 14, 2020 CRK has served as a clinical advisor, with no financial compensation, for OpenBiome since 2013; she is a local principal investigator for the PRISM-3 clinical trial, for which her institution receives some salary support for a research coordinator and compensation from Finch Therapeutics Group for each patient enrolled. HS reports personal fees from Danone, Enterome, Takeda, AbbVie, Roche, Amgen, Danone, BiomX, Ferring, BMS, Astellas, MSD, Novartis, Tillotts Pharma, and Biose, and grants from Biocodex, Danone, and BiomX, and is a co-founder of Exeliom Biosciences. ZK is an employee and shareholder of Finch Therapeutics and is an unpaid special advisor for OpenBiome. SCN reports grants from Ferring and personal fees from Takeda, AbbVie, Janssen, and Tillotts. MF reports personal fees from Finch Therapeutics Group, Rebiotix, Takeda, AbbVie, and Janssen. JRA reports personal fees from Finch Therapeutics and a non-financial relationship with OpenBiome as a scientific advisor. FZ reports grants from the non-profit China Microbiota Transplantation System (fmtBank) and a patent for GenFMTer for separating microbiota issued to FMT Medical. JK reports grants from Vedanta Biosciences and is an unpaid board member of the non-profit Netherlands Donor Feces Bank. SPC reports non-financial support from Janssen and personal fees from Shire, Ferring, Microbiotica, and Pfizer. AG reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and Sanofi S.p.A, personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A, and personal fees for acting on advisory boards for VSL3 and Eisai. GI, BHM, LM, MS, HT, and GC declare no competing interests. Correction to Lancet Gastroenterol Hepatol 2020; 5: 430–31Ianiro G, Mullish BH, Kelley CR, et al. Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel. Lancet Gastroenterol Hepatol 2020; 5: 430–31—In this Comment, the declaration of interests statement should read: "CRK has served as a clinical advisor, with no financial compensation, for OpenBiome since 2013; she is a local principal investigator for the PRISM-3 clinical trial, for which her institution receives some salary support for a research coordinator and compensation from Finch Therapeutics Group for each patient enrolled. Full-Text PDF SARS-CoV-2 vaccines and donor recruitment for FMTDue to its clear benefits in the management of recurrent Clostridioides difficile infection, faecal microbiota transplantation (FMT) has been advocated by the gastroenterological community as a non-postponable procedure to be continuously delivered during the COVID-19 pandemic.1 Full-Text PDF