PT  - JOURNAL ARTICLE
AU  - Ramy Arnaout
AU  - Rose A. Lee
AU  - Ghee Rye Lee
AU  - Cody Callahan
AU  - Christina F. Yen
AU  - Kenneth P. Smith
AU  - Rohit Arora
AU  - James E. Kirby
TI  - SARS-CoV2 Testing: The Limit of Detection Matters
AID  - 10.1101/2020.06.02.131144
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.02.131144
4099  - http://biorxiv.org/content/early/2020/06/04/2020.06.02.131144.short
4100  - http://biorxiv.org/content/early/2020/06/04/2020.06.02.131144.full
AB  - 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.