key: cord-0878531-fok474fc
authors: Olesen, Scott W.; Zaman, Amanda; Osman, Majdi; Ramakrishna, Bharat
title: Modelling donor screening strategies to reduce the risk of SARS-CoV-2 via fecal microbiota transplantation
date: 2020-06-24
journal: bioRxiv
DOI: 10.1101/2020.06.24.169094
sha: ace296dba7e3caed4b9fbaca4017d042697a990e
doc_id: 878531
cord_uid: fok474fc

The potential for transmission of SARS-CoV-2 shed in stool via fecal microbiota transplantation is not yet known, and the effectiveness of various testing strategies to prevent FMT-based transmission has also not yet been quantified. Here we use a mathematical model to simulate the utility of different testing strategies.

Fecal microbiota transplantation (FMT), the instillation of stool from a healthy donor into a 8 patient's gut, is a recommended therapy for the most common hospital-acquired infection in the 9

United States, Clostridioides difficile, and is being explored as an experimental therapy for 10 dozens of other conditions. 1,2 As with all human-derived therapies, the safety of FMT depends 11 on screening donors to prevent transmission of pathogens via the procedure, 3 and screening 12 guidelines must be continually updated to account for emerging pathogens. 13 14 SARS-CoV-2, the virus that causes COVID-19, is primarily considered a respiratory pathogen, 15 but evidence suggests that the virus is able to independently replicate in the gut, raising the 16 possibility of transmission via the fecal oral-route or via FMT. 4 Practitioners 4,11 and regulators 12 17 have therefore called for screening of FMT donors for SARS-CoV-2. However, because of the 18 virus's long incubation period, the high proportion of infected individuals that are asymptomatic, 6 19 and the long period in which apparently-recovered individuals can continue to shed virus in their 20 stool, 7-10 screening FMT donors using COVID-19 clinical assessment alone is insufficient. 21

Despite the consensus that FMT donors should be screened for SARS-CoV-2, the optimal 23 available strategy for detecting asymptomatic carriage among FMT donors is unclear. donors are assumed to have tested negative on all screens be unexposed U when they enroll 47 on the first day of the simulation. Each day, the donor has a probability of becoming infected I1; 48 this is the incidence of infection. We ignore any latent period, as it is not relevant to the model. A 49 proportion of infected donors develop symptoms. If a donor becomes symptomatic, their 50 donations from the 14 days prior to onset of symptoms are rejected, and the donor is removed. 51

We assume that an asymptomatic donor in phase I1 has detectable virus in their nasopharynx but is not shedding detectable loads virus in stool and has not developed detectable IgG 53 antibodies (Supplemental Table 1 To evaluate the effectiveness of different testing strategies, 10,000 simulations were run for 78 each of 3 incidences (1 infection per 1,000 people per day; 1 per 10,000; 1 per 100,000) and 79 each of 9 screening strategies (stool testing only at 28-day intervals or 14-day intervals, or 80 testing every stool; nasopharyngeal swabs only; nasopharyngeal swabs and stool at each of the 81 3 stool-testing intervals; nasopharyngeal swabs and serology; nasopharyngeal swabs, serology, 82 and every stool). A sensitivity analysis was run to evaluate the dependence of the model 83 outcomes on input parameters. In 10,000 simulations, parameters were varied over the 84 hypercube bounded by the upper and lower parameter estimates in Table 1 . strategies involved testing every stool, while the least sensitive strategies were to use 126 nasopharyngeal swab alone or to test stool at 28-day intervals. More stringent tests were more 127 sensitive but also less specific, and the most appropriate strategy must be determined by a 128 balance between the necessary stringency and logistical considerations like resourcing. 

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