Investigation of suspected false positive norovirus results on a syndromic gastrointestinal multiplex molecular panel

•From February 2023 to May 2024 a total of 11,015 BioFire® FilmArray® Gastrointestinal panel (BF-GIP) tests were performed across 6 laboratories.•The proportion of potential false positive norovirus results was 27.4 % (215/784) based on confirmatory testing on a second molecular method.•When using whole genome sequencing (WGS), 64/65 results agreed with confirmatory testing on a second molecular method.•150 norovirus melting curves were reviewed and they did not accurately predict false positives. Suspected false positive norovirus results occurred after introduction of the BioFire® FilmArray® Gastrointestinal panel (BF-GIP) into 6 laboratory sites, in British Columbia, Canada. The primary objective was to investigate suspected false positive results by performing additional molecular assays and whole genome sequencing (WGS). The second objective was to determine if melting curve review could predict false positive results. From February 2023 to May 2024, the proportion of potential false positive norovirus results from the BF-GIP was calculated based on confirmatory testing using alternate molecular method. A subset of 65 norovirus BF-GIP positive specimens, including 35 negatives and 30 positives on additional molecular assays, underwent WGS. Melting curves appearances from 150 specimens were reviewed. Overall, 215/784 (27.4 %) BF-GIP norovirus results were suspected to be false positives. When using WGS, 64/65 results were in agreement with confirmatory testing. Notably, 35 specimens negative on confirmatory testing and suspected to be BF-GIP norovirus false positive results were undetectable by WGS. Melting curves did not accurately predict false positives, since 20/72 (27.8 %) had typical appearances upon review. BF-GIP produces false positive results for norovirus, which cannot be predicted by melting curve review.