SARS-CoV2 Testing: The Limit of Detection Matters

BioRxiv : the Preprint Server for Biology
Ramy ArnaoutJ. E. Kirby

Abstract

Resolving the COVID-19 pandemic requires diagnostic testing to determine which individuals are infected and which are not. The current gold standard is to perform RT-PCR on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of ~100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss more infected patients, resulting in more false negatives. However, the false-negative rate for a given LoD remains unknown. Here we address this question using over 27,500 test results for patients from across our healthcare network tested using the Abbott RealTime SARS-CoV-2 EUA. These results suggest that each 10-fold increase in LoD is expected to increase the false negative rate by 13%, missing an additional one in eight infected patients. The highest LoDs on the market will miss a majority of infected patients, with false negative rates as high as 70%. These results suggest that choice of assay has meaningful clinical and epidemiological consequences. The limit of detection matters.

Citations

Aug 21, 2020·Nature Biotechnology·Matthew J MacKayChristopher E Mason
Sep 15, 2020·Molecular Diagnosis & Therapy·Thomas UsherwoodAnubhav Tripathi
Sep 2, 2020·Emerging Microbes & Infections·Elisabetta RivaGiuseppe Patti
Jan 17, 2021·Genes·Gustavo Barcelos BarraLídia Freire Abdalla Nery
May 6, 2021·Nature Reviews. Genetics·Tim R Mercer, Marc Salit
May 18, 2021·Frontiers in Cellular and Infection Microbiology·Uyanga Ganbaatar, Changchun Liu
Jun 3, 2021·Biosensors·Niharika GuptaBansi D Malhotra

Methods Mentioned

BETA
nucleic acid amplification
PCR

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