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A Method for Detection of SARS-CoV-2 RNA in Healthy Human Stool: A Validation Study

Scientists from the U.S. Food and Drug Administration (FDA), in collaboration with scientists from academia, have published the results of a study that evaluated a method for the detection of SARS-CoV-2 RNA in fecal samples. The study included determination of the assay sensitivity, the effect of storing fecal samples prior to analysis, and the implementation of the test to detect virus in the stool of infected individuals (5 months to 20 years of age). This method has potential uses in stool donor screening, sewage monitoring, and further research into the impact of fecal shedding on the epidemiology of this pandemic.

The new findings are important because the COVID-19 pandemic has disrupted clinical trials investigating use of fecal microbiota for transplantation (FMT) for the treatment of various diseases and health conditions. The pandemic has also affected the availability of FMT products used to treat Clostridioides difficile (C. diff) infections not responsive to standard therapies under FDA’s policy of enforcement discretion. FDA developed the enforcement discretion policy to specifically accommodate the immediate needs of very sick patients with C. diff infection that is not responsive to standard therapies; in these cases, illness can be life-threatening. The enforcement discretion policy is explained in a guidance document that FDA issued in July 2013.

Early in the pandemic, research found that the SARS-CoV-2 virus was shed in the stool of infected individuals, leading to concerns about the potential for transmission of the virus through FMT products. Because of the potential risk of transmission of SARS-CoV-2 through FMT, FDA issued a Safety Alert on March 23, 2020. The alert outlines additional safety protections that are needed for any investigational use of FMT, whether under an Investigational New Drug Application (IND) on file with the FDA or under FDA’s enforcement discretion policy. On April 9, 2020, FDA provided important updates related to the potential risk of transmission of SARS-CoV-2 via FMT and conveyed additional protections for investigational use of FMT during the global pandemic of COVID-19. FDA’s Safety Alerts communicated, in part, that there should be no clinical use of FMT products manufactured from stool donated on or after December 1, 2019, until additional screening and testing procedures have been implemented for donor qualification programs.

Although numerous molecular tests have been validated for the detection of SARS-CoV-2 viral RNA in respiratory samples, no fully validated testing options for use with stool have been established. In order to facilitate the accurate detection of SARS-CoV-2 viral RNA in fecal samples, FDA scientists and their collaborators worked to modify a SARS-CoV-2 testing protocol for use in stool and then study the test to determine its utility. They determined the limit of detection as well as the effects of storing stool samples on the ability of the assay to detect low levels of virus in stool samples. Additionally, they performed the method on samples of stool from individuals with symptomatic COVID-19 disease who were previously diagnosed by respiratory testing methods. The test successfully detected SARS-CoV-2 RNA in the stool of 48% of symptomatic individuals tested.

Their work therefore provides a new method for detection of SARS-CoV-2 viral RNA in stool. Of note, this test does not have FDA authorization; however, following appropriate qualification and/or validation at individual test locations, it can potentially be implemented for a variety of purposes, including stool donor screening, sewage monitoring, and clinical studies assessing viral shedding.

Title

A method for detection of SARS-CoV-2 RNA in healthy human stool: a validation study

Lancet Microbe, March 31, 2021.  DOI:https://doi.org/10.1016/S2666-5247(21)00059-8

Authors: Michael P. Coryell, PhDa; Mikhail Iakiviak, PhDb; Nicole Pereira, PhDb; Pallavi P. Murugkar, PhDb; Jason Rippe, JDc; David B. Williams, BSc; Taylor Heald-Sargent, MDc, d; L. Nelson Sanchez-Pinto, MDc, d; Jairo Chavez, BSc, d; Jessica L. Hastie, PhD a; Rosa L. Sava BSa;  Christopher Z. Lien, M.S.e;  Tony T. Wang, PhDe; William J. Muller, MDc, d; Prof Michael A. Fischbach, PhD b; and Paul E. Carlson Jr., PhDa*

Affiliations:

a Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

b Department of Bioengineering and ChEM-H, Stanford University, 290 Jane Stanford Way, Stanford, CA 94305, USA

c Division of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital, 225 E. Chicago Ave, Chicago, Illinois 60611

d Northwestern University Feinberg School of Medicine, 225 E. Chicago Ave, Chicago, Illinois 60611

e Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue Silver Spring, Maryland, 20993, USA.

* Corresponding author: Paul E. Carlson Jr. Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration,10903 New Hampshire Avenue, Silver Spring, Maryland 20993, USA. Tel: 240-402-4090; E-mail: paul.carlson@fda.hhs.gov

 
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