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

Abstract

\n 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\u2009=\u20091033), Abbott (n\u2009=\u2009806), Diasorin (n\u2009=\u20091034) and Euroimmun (n\u2009=\u2009175) 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\u2009AU/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.\n