COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays
2020; 40(6): 439-447
Ann Lab Med 2021; 41(4): 424-428
Published online July 1, 2021 https://doi.org/10.3343/alm.2021.41.4.424
Copyright © Korean Society for Laboratory Medicine.
1Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea; 2Microbiotix Corporation, Seoul, Korea; 3Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Correspondence to: Dongeun Yong, M.D., Ph.D.
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.
Keywords: Korea, Fecal microbiota transplantation, Fecal microbiota bank, Donor screening
Fecal microbiota transplantation (FMT) is widely used as a last resort treatment for
Many European and North American fecal microbiota banks have recently reported their donor screening outcomes, and these data have provided insights for establishing evidence-based FMT consensus reports [4-10,12]. However, there is a paucity of such reports from Asian fecal microbiota banks, despite there being numerous publications on FMT clinical outcomes [13, 14]. This report presents the donor screening outcomes from a fecal microbiota bank in Korea (Microbiotix Corporation, Seoul, Korea).
In November 2016, Microbiotix Corporation, a university hospital-affiliated startup company, founded a non-profit fecal microbiota bank in collaboration with physicians from various disciplines (laboratory medicine, gastroenterology, pulmonology, and infectious disease). This fecal microbiota banking project was approved by the Severance Hospital Institutional Review Board, Seoul, Korea (IRB No. 4-2016-0850). Donors were recruited through poster advertisements at the Yonsei University Health System starting August 2017. Individuals interested in fecal donation were invited for a two-stage donor-screening process (stage 1, clinical assessment; stage 2, laboratory tests) created based on the Korean Transfusion Guidelines and the European and American FMT donor screening protocols [4, 5, 9, 15].
A summary of the donor screening criteria is provided in Table 1. All donor candidates provided informed consent to participate in the study. An in-person clinical assessment (stage 1) was carried out to evaluate the donor candidates for general health and gastrointestinal conditions and for any risk factors for transmissible diseases. This process was performed by a nurse clinical research coordinator and was verified by a laboratory medicine specialist. At stage 2, donor candidates underwent serological/fecal screening, a urea breath test (UBT), and chest (posteroanterior) radiography to identify underlying health conditions and potentially transmissible pathogens. Although FMT is recognized as a safe and effective treatment with manageable adverse effects (e.g., bloating, cramping, and diarrhea), it is crucial to acknowledge previously reported adverse effects possibly associated with FMT [16, 17]. A previous study reported two cases of FMT-associated ESBL-producing
The qualification of 62 candidates to serve as potential FMT donors was assessed from August 2017 through June 2020 (Fig. 1). Forty-six (74%) candidates were excluded based on the pre-screening questionnaire responses. High body mass index (BMI; >25) was the most common reason for donor exclusion (16 individuals), followed by atopy, asthma, and allergy history (15 individuals). The remaining 16 candidates underwent serological/fecal screening, and four (25%) failed to meet laboratory test criteria. Of the donor candidates excluded at stage 2, three candidates (75%) had abnormal blood test results and one carried ESBL-producing
All fecal material from the qualified donors was processed into slurries and quarantined for one month to ensure that it passed the monthly re-qualification process. The re-qualification process involved the same clinical assessment and laboratory test stages as the initial screening process. After the re-qualification process, nine candidates (75%) did not meet the laboratory test criteria as they showed risks for infectious diseases (five with MDRO, four with
Regular screening of FMT donors is crucial, as it serves as an ongoing safety control measure.
To the best of our knowledge, this is the first report to outline the donor screening process and outcomes at a fecal microbiota bank in Asia. After establishing donor screening criteria based on pre-existing protocols and consensus reports, the FMT donor qualification rate was 19%. High BMI (>25; N=16) and abnormal serological test results (increased total bilirubin level (2.2 mg/dL) and positive antinuclear antibody test; N=4) were the major criteria for donor exclusion based on clinical assessment and laboratory tests, respectively. A monthly donor re-qualification process contributed to a high overall donor exclusion rate. It resulted in identifying new risk factors, including carriage of infectious agents (
Part of this work was presented at the Laboratory Medicine Congress & Exhibition 59th annual meeting, November 2018. We especially wish to thank Professors Jae Hee Cheon, Jun Yong Choi, Su Jin Jeong, Hong Ko, Sang Kil Lee, Moo Suk Park, and Soo Jung Park from Yonsei University College of Medicine for collaborative discussions regarding the development of the FMT donor screening protocol as well as the laboratory staff of the Department of Laboratory Medicine at Severance Hospital for assistance with the laboratory examination of donor stool samples.
Chin HS, Kim YH, and Yong D designed the study; Seo HS, Chin HS, Moon HS, Kim YH, and Kim KN collected the clinical samples and analyzed and interpreted the data; and Seo HS, Nguyen LP, and Yong D wrote the manuscript. All authors read and approved the final manuscript.
Seo HS, Chin HS, Moon HS, Kim KN, and Yong D are partly employed by Microbiotix Corporation. Kim YH is a former employee of Microbiotix Corporation. No other potential conflicts of interest relevant to this article were reported.
This study was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Korea (grant No.: HI14C1324); the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the Agricultural Microbiome R&D Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA)(918003-4); and a clinical research grant from Microbiotix Inc.