Evaluation of SARS-CoV-2 antibody point of care devices in the laboratory and clinical setting

Abstract

SARS-CoV-2 antibody tests have been marketed to diagnose previous SARS-CoV-2 infection and as a test of immune status. There is a lack of evidence on the performance and clinical utility of these tests. We aimed to carry out an evaluation of 14 point of care (POC) SARS-CoV-2 antibody tests. Serum from participants with previous RT-PCR (real-time polymerase chain reaction) confirmed SARS-CoV-2 infection and pre-pandemic serum controls were used to determine specificity and sensitivity of each POC device. Changes in sensitivity with increasing time from infection were determined on a cohort of study participants. Corresponding neutralising antibody status was measured to establish whether the detection of antibodies by the POC device correlated with immune status. Paired capillary and serum samples were collected to ascertain whether POC devices performed comparably on capillary samples. Sensitivity and specificity varied between the POC devices and in general did not meet the manufacturers’ reported performance characteristics, which signifies the importance of independent evaluation of these tests. The sensitivity peaked at ≥20 days following onset of symptoms, however sensitivity of 3 of the POC devices evaluated at extended time points showed that sensitivity declined with time. This was particularly marked at >140 days post infection. This is relevant if the tests are to be used for sero-prevalence studies. Neutralising antibody data showed that positive antibody results on POC devices did not necessarily confer high neutralising antibody titres, and that these POC devices cannot be used to determine immune status to the SARS-CoV-2 virus. Comparison of paired serum and capillary results showed that there was a decline in sensitivity using capillary blood. This has implications in the utility of the tests as they are designed to be used on capillary blood by the general population.

Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study

“…Although this is in line with previous reports in the literature (13,14,20), previous analysis did not include all the same assay characteristics that we include, and did not quantify the effects of each characteristic in a simultaneous model fi. The striking differences between the different types of assays reported here outlines the need to do assay-specific corrections for seroreversion.…”

“…Roche rapid test (20) Orient Gene Biotech (42) SenASTrIS test (97,98) Siemens Advia Centaur (52,99) Siemens Advia anti-RBD Vitros Ortho (not total antibodies) (13,(104)(105)(106)(107) Vitros Ortho (total antibodies) (13,14) Wantai (14,69,108,109)…”

“…Although the time-varying sensitivity of serology assays has been evaluated in some previous studies, these are in general limited to either small numbers of assays, or short time spans (13,14,(20)(21)(22)(23). This limits the ability of these previous studies to properly quantify how different assay characteristics determine seroreversion, the variability of seroreversion across assays, and to provide general guidelines to account for seroreversion.…”

“…Strikingly, despite the widespread use of serosurveys and their well known limitations, there is a lack of guidelines to correct for seroreversion in the SARS-CoV-2 literature (17,18). Time-varying sensitivity of seroassays has been evaluated in previous studies, but these are limited to few assays or short time spans (14,15,(21)(22)(23)(24). Thus, these studies could not quantify the effect of different assay characteristics on seroreversion, or provide general guidelines to correct for it.…”

“…Time-varying sensitivity of seroassays has been evaluated in previous studies, but these are limited to few assays or short time spans (14,15,21–24). Thus, these studies could not quantify the effect of different assay characteristics on seroreversion, or provide general guidelines to correct for it.…”