Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study

Abstract

Background: SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy. Methods: In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19 TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices. Findings: We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19 TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations ("spectrum effects"), but the extent of this varied by device. Interpretation: The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.

Evaluation of the Roche SARS-CoV-2 Rapid Antibody Test in Samples from Vaccinated Individuals

“…In addition, the Elecsys Anti-SARS-CoV-2 S assay preferentially detects high-affinity IgG antibodies that compete with IgM antibodies ( 23 ), contributing to the lower agreement rates with IgM results. In agreement with previous research on the use of lateral flow assays in unvaccinated individuals ( 38 , 39 ), we also report lower evaluator concordance when reading IgM compared with IgG bands. Jones and colleagues found that IgM bands are often weak positives ( 39 ), consistent with our data in vaccinated individuals, potentially resulting in an increased likelihood of a miscall and contributing to the low reader agreement.…”

SARS-CoV-2 seroepidemiological study in healthcare workers and discordant results using seven different diagnostic methods

“…In recent publications, that assessed the concordance of the results of different high-throughput automated immunoassays (including our used automated immunoassays), ELISA (included in this study) and RIC (not included) assays, a higher concordance than in our result depending on the used assay was recorded [ 28 ] [ 29 ].…”

Indicators of recent COVID-19 infection status: findings from a large occupational cohort of staff and postgraduate research students from a UK university

“…Antibody testing in KCL CHECK used an IgG/IgM test kit based on “lateral flow” technology, sent to participants, which was simple to use and has high validity (under lab conditions) [ 31 ]. Antibody tests can give false positives in up to 2 per 100 tests, through cross-reactivity with antibodies unrelated to SARS-CoV-2, [ 12 , 21 ] which can be problematic in large studies with low prevalence. Testing negative after having had COVID-19 is also a concern, since small numbers of people do not produce anti-spike antibodies, [ 32 , 33 ] they are detected more inconsistently in mild and asymptomatic COVID-19, [ 31 , 34 , 35 ] and decline over time [ 36 – 38 ].…”

“…There are three key limitations of which to be aware. The first regards the antibody test lateral flow cassettes, which are designed for use by a trained person rather than the general public, and are known to be less sensitive and more inconsistent when testing outside the laboratory and on capillary blood [ 21 , 35 ]. Secondly, as we did not exclude people with missing longitudinal survey we had incomplete data about self-reported items after the baseline.…”

“…The performance of this test (under laboratory conditions) has been shown to be good. For example, using samples from 268 keyworkers who self-reported positive COVID-19 antigen/PCR tests and 1,995 historical samples, it had 94.0% sensitivity and 97.0% specificity, also showing 96.3% agreement with the SAR-CoV-2 spike antibody enzyme-linked immunoassay (ELISA) result for 2,847 keyworkers [ 21 ]. An internal pilot demonstrated that participants could use the test cassette without specific training [ 22 ].…”