Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 sero-prevalence survey

Abstract

Background Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required. Methods Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by RT-PCR and were ≥21d from symptom-onset. In phase I we evaluated five LFIAs in clinic (with finger-prick) and laboratory (with blood and sera) in comparison to a) PCR-confirmed infection and b) presence of SARS-CoV-2 antibodies on two “in-house” ELISAs. Specificity analysis was performed on 500 pre-pandemic sera. In phase II, six additional LFIAs were assessed with serum. Findings 95% (95%CI [92.2, 97.3]) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8/11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21%-92% vs PCR-confirmed cases and 22%-96% vs composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2% - 99.8%). Interpretation LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI [97.1, 99.4])), moderate sensitivity (84.4% with fingerprick (95%CI [70.5, 93.5])), and moderate concordance, suitable for seroprevalence surveys.