An evaluation of 4 commercial assays for the detection of SARS-CoV-2 antibodies in a predominantly mildly symptomatic low prevalence Australian population

Abstract

A total of 1080 individual patient samples (158 positive serology samples from confirmed, predominantly mildly symptomatic COVID-19 patients and 922 serology negative including 496 collected pre-COVID) from four states in Australia were analysed on four commercial SARS-CoV-2 serological assays targeting antibodies to different antigens (Roche Elecsys and Abbott Architect: nucleocapsid; Diasorin Liaison and Euroimmun: spike). A subset was compared to immunofluorescent antibody (IFA) and micro-neutralisation. Sensitivity and specificity of the Roche (n = 1033), Abbott (n = 806), Diasorin (n = 1034) and Euroimmun (n = 175) were 93.7%/99.5%, 90.2%/99.4%, 88.6%/98.6% and 91.3%/98.8%, respectively. ROC analysis with specificity held at 99% increased the sensitivity for the Roche and Abbott assays from 93.7% to 98.7% (cut-off 0.21) and 90.2% to 94.0% (cut-off 0.91), respectively. Overall seropositivity of samples increased from a maximum of 23% for samples 0-7days-post-onset of symptoms (dpos), to 61% from samples 8-14dpos and 93% from those >14dpos. IFA and microneutralisation values correlated best with assays targeting antibodies to spike protein with values >80 AU/mL on the Diasorin assay associated with neutralising antibody. Detectable antibody was present in 22/23 (96%), 20/23 (87%), 15/23 (65%) and 9/22 (41%) patients with samples >180dpos on the Roche, Diasorin, Abbott and microneutralisation assays respectively. Given the low prevalence in this community, two-step algorithms on initial positive results saw an increase in the positive predictive value (PPV) of positive samples (39%-65% to ≥98%) for all combinations. Similarly accuracy increased from a range of 98.5%-99.4% to ≥99.8% assuming a 1% seroprevalence. Negative predictive value (NPV) was high (≥99.8%) regardless of which assay was used initially.

COVID‐19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B‐lymphocytosis; humoural and cellular immunity

“…Interestingly, the association between reduced prevaccination IgA and failure to respond (OR 3.30, p = 0.043) becomes statistically significant, and hence coincides with data reported by Parry et al 20 and Herishanu et al 21 Both those two reports employed the Roche Elecsys® (Roche Diagnostics International AG, Rotkreuz, Switzerland) electrochemiluminescence immunoassay for measuring serologic responses while we used the Abbott Diagnostics assay. Differences in assay performance 33,34 may contribute to differences between our data and those of Parry et al 20 and Herishanu et al 21 CLL and immunocompromised individuals are unable to clear certain viruses such as rhinovirus. 11,12 For the much more serious COVID-19, long-term shedding of live virus has now been documented in CLL.…”

COVID-19 Vaccine Failure in Chronic Lymphocytic Leukemia and Monoclonal B-Lymphocytosis; Humoral and Cellular Immunity

“…Both those two reports employed the Roche Elecsys® electrochemiluminescence immunoassay for measuring serologic responses while we used the Abbott Diagnostics assay. Differences in assay performance 33,34 may contribute to discrepancies between our data and those of Parry et al 20 and Herishanu et al 21 .…”

Evaluation of the performance of SARS‐­CoV­‐2 antibody assays for a longitudinal population­based study of COVID‐­19 spread in St. Petersburg, Russia

“…However, researchers have raised several concerns regarding the non­response bias, the non­representative sampling, and the use of non­validated tests for SARS‐­CoV­‐2 antibodies detection 4 . The first two issues can be addressed by appropriate study design and population sampling strategies 5,6 The latter problem requires the assessment of sensitivity and specificity of antibody assays to guide the correction of serological study results 7–11 . Additional requirements for antibody tests are being lodged for longitudinal serologic studies, but manufacturers rarely report the evaluation of the long­term test performance, for example, decreased long­term sensitivity is an issue that could bias the evaluation of immune response durability 12,13 …”