The journey towards safely restarting faecal microbiota transplantation services in the UK during the COVID-19 era
Authors: Mohammed Nabil Quraishi, Sahida Shabir, Susan E Manzoor, Christopher A Green, Naveen Sharma, Andrew D Beggs, Tariq H Iqbal
Journal: The Lancet Microbe (2021)

Faecal microbiota transplantation (FMT) is a potentially life-saving treatment for patients with refractory and recurrent Clostridioides difficile infection with cure rates of 90%.1Mullish BH Quraishi MN Segal JP et al.The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.Gut. 2018; 67: 1920-1941Crossref PubMed Scopus (194) Google Scholar Substantial implications with regard to the safe provision of FMT were made evident with emerging reports of detectable SARS-CoV-2 virus in stool even before the declaration of the COVID-19 pandemic.2Zhang JJ Dong X Cao YY et al.Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.Allergy. 2020; 75: 1730-1741Crossref PubMed Scopus (2426) Google Scholar Furthermore, data suggesting prolonged and potentially infectious faecal virus shedding in stool samples in asymptomatic carriers who tested negative on nasopharyngeal swabs meant FMT donor screening protocols could no longer rely on symptoms and a nasopharyngeal swab alone.3Hindson J COVID-19: faecal-oral transmission?.Nat Rev Gastroenterol Hepatol. 2020; 17: 259Crossref PubMed Scopus (235) Google Scholar, 4Wu Y Guo C Tang L et al.Prolonged presence of SARS-CoV-2 viral RNA in faecal samples.Lancet Gastroenterol Hepatol. 2020; 5: 434-435Summary Full Text Full Text PDF PubMed Scopus (1099) Google Scholar The Medicine and Healthcare Regulatory Agency approved University of Birmingham Microbiome Treatment Centre (UoBMTC), was the first to mandate SARS-CoV-2 testing of stool as part of donor screening and called for a halt of FMT production globally until a validated stool assay was available5Green CA Quraishi MN Shabir S et al.Screening faecal microbiota transplant donors for SARS-CoV-2 by molecular testing of stool is the safest way forward.Lancet Gastroenterol Hepatol. 2020; 5: 531Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar with an evidence-based international consensus on guidance for donor screening being published.6Ianiro G Mullish BH Kelly CR et al.Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.Gut. 2020; 69: 1555-1563Crossref PubMed Scopus (101) Google Scholar FMT production at UoBMTC was paused in March, 2020 and FMT that was already manufactured from February, 2020, was quarantined. Following consensus agreements with FMT providers globally and a review of updated evidence on safety and efficacy, the shelf life of FMT collected before December, 2019, was extended from 6 months to 12 months. This allowed our centre to treat a further 68 patients with recurrent C difficile infection until the stocks were exhausted by August, 2020. In conjunction with FMT providers globally, we established new donor screening protocols that now include multiple levels of questionnaire-based and molecular screening for SARS-CoV-2 infection or enteric carriage at several timepoints of the donor and FMT production pathway (appendix). However, restarting FMT manufacture principally relied on a validated assay for detection of SARS-CoV-2 in stool, which is not commercially available. Our centre worked towards validating a sensitive and specific assay that uses multiple technologies in parallel for the detection of SARS-CoV-2 in stool.7Mansoor S Zaman S Whalley C et al.Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions.medRxiv. 2021; (wpublished online Feb 3.April 2015) (preprint).https://doi.org/10.1101/2021.02.02.21250934Google Scholar A combination that includes real-time PCR, digital droplet PCR, and nanopore sequencing technology was validated with stool viral spiking experiments and testing of stool samples from more than 100 COVID-19 positive and COVID-19 negative hospitalised patients (on the basis of nasopharyngeal PCR). The assay was approved by the Medicine and Healthcare Regulatory Agency in January, 2021, and has enabled the resumption of donor screening and FMT services in the COVID-19 era. We have now released quarantined FMT aliquots from those manufactured in February, 2020, and have treated several patients successfully. Although FMT is a safe and a highly effective treatment for recurrent C difficile infection, FDA safety alerts in the USA, following serious adverse events as a result of transmission of enteric pathogens, emphasise that there can be no room for complacency.8US FDAImportant safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse reactions due to transmission of multi-drug resistant organisms.https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverseDate: June 13, 2019Date accessed: February 1, 2021Google Scholar Although our revised protocols are highly robust in screening asymptomatic carriers of SARS-CoV-2, both FMT providers and users need to remain vigilant for new threats during the changing viral pandemic and beyond. We declare no competing interests. Download .pdf (.33 MB) Help with pdf files Supplementary appendix