Validation of a rapid SARS-CoV-2 antibody test in general practice

Abstract

Objectives: To validate a rapid serological test (RST) for SARS-CoV-2 antibodies used in seroprevalence studies in healthcare providers, including primary healthcare providers (PHCPs) in Belgium.

Design: A phase III validation study of the RST (OrientGene) within a prospective cohort study.

Setting: Primary care in Belgium.

Participants: Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages patients were eligible in the seroprevalence study. For the validation study, all participants who tested positive (376) on the RST at the first testing timepoint (T1) and a random sample of those who tested negative (790) and unclear (24) were included.

Intervention: At T2, 4 weeks later, PHCPs performed the RST with fingerprick blood (index test) immediately after providing a serum sample to be analysed for the presence of SARS-CoV-2 immunoglobulin G antibodies using a two-out-of-three assay (reference test).

Primary and secondary outcome measures: The RST accuracy was estimated using inverse probability weighting to correct for missing reference test data, and considering unclear RST results as negative for the sensitivity and positive for the specificity. Using these conservative estimates, the true seroprevalence was estimated both for T2 and RST-based prevalence values found in a cohort study with PHCPs in Belgium.

Results: 1073 paired tests (403 positive on the reference test) were included. A sensitivity of 73% (a specificity of 92%) was found considering unclear RST results as negative (positive). For an RST-based prevalence at T1 (13.9), T2 (24.9) and T7 (70.21), the true prevalence was estimated to be 9.1%, 25.9% and 95.7%, respectively.

Conclusion: The RST sensitivity (73%) and specificity (92%) make an RST-based seroprevalence below (above) 23% overestimate (underestimate) the true seroprevalence.

Trial registration number: NCT04779424.

Keywords: COVID-19; infectious diseases; primary care.

Figure 1

Participant flow. PHCP, primary healthcare provider; RST, rapid serological test.

Figure 2

The estimated true prevalence* and 95% confidence intervals† for imperfect tests‡ based on prevalence values during our cohort study among primary healthcare providers (PHCPs) between 24 December 2020 and 26 December 2021. Since the true prevalence cannot exceed 100%, but the limited basic calculation of Rogan -Gladen, which uses a fixed sensitivity and specificity, can result in true prevalence values greater than 100%, these implausible values are clearly marked in grey. * Rogan -Gladen method. †Calculated with the Wilson method. ‡Sensitivity of 72.9% and specificity 91.9%.