Petersen, Irene, Crozier, Alexander, Buchan, Iain 
ORCID: 0000-0003-3392-1650, Mina, Michael ORCID: 0000-0002-0674-5762 and Bartlett, Jonathan
(2021)
Recalibrating SARS-CoV-2 antigen rapid lateral flow test relative sensitivity from validation studies to absolute sensitivity for detecting individuals with live virus.
2021.03.19.21253922-.
Abstract
Testing for SARS-CoV-2 internationally has focused on COVID-19 diagnosis among symptomatic individuals using reverse transcriptase polymerase chain reaction (PCR) tests. Recently, however, SARS-CoV-2 antigen rapid lateral flow tests (LFT) have been rolled out in several countries for testing asymptomatic individuals in public health programmes. Validation studies for LFT have been largely cross-sectional, reporting sensitivity, specificity and predictive values of LFT relative to PCR. However, because PCR detects genetic material left behind for a long period when the individual is no longer infectious, these statistics can under-represent sensitivity of LFT for detecting infectious individuals, especially when sampling asymptomatic populations. LFTs (intended to detect individuals with live virus) validated against PCR (intended to diagnose infection) are not reporting against a gold standard of equivalent measurements. Instead, these validation studies have reported relative performance statistics that need recalibrating to the purpose for which LFT is being used. We present an approach to this recalibration. We derive a formula for recalibrating relative performance statistics from LFT vs PCR validation studies to give likely absolute sensitivity of LFT for detecting individuals with live virus. We show the differences between widely reported apparent sensitivities of LFT and its absolute sensitivity as a test of presence of live virus. After accounting for within-individual viral kinetics and epidemic dynamics within asymptomatic populations we show that a highly performant test of live virus should show a LFT-to-PCR relative sensitivity of less than 50% in conventional validation studies, which after re-calibration would be an absolute sensitivity of more than 80%. Further studies are needed to ascertain the absolute sensitivity of LFT as a test of infectiousness in COVID-19 responses. These studies should include sampling for viral cultures and longitudinal series of LFT and PCR, ideally in cohorts sampled from both contacts of cases and the general population.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Infectious Diseases, Prevention, Biodefense, Emerging Infectious Diseases, Vaccine Related, 4 Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Infection, 3 Good Health and Well Being |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Population Health |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Feb 2022 09:53 |
| Last Modified: | 15 Mar 2024 15:22 |
| DOI: | 10.1101/2021.03.19.21253922 |
| Open Access URL: | https://www.dovepress.com/recalibrating-sars-cov-2... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3149511 |
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