Paired Sensitivity Analysis of Four SARS-CoV-2 Serological Immunoassays
in a Longitudinal Cohort of Convalescent Hospital Staff
Abstract
BACKGROUND: SARS-CoV-2 serological testing has seen extensive academic
and clinical use from investigating correlates of immunity to
seroprevalence, convalescent plasma and vaccine trials. Interpretation
of these studies will depend on robust validation of the longitudinal
sensitivities of serological assays. OBJECTIVE: To conduct longitudinal
sensitivity analysis on four different SAR-CoV-2 antibody assays in a
convalescent cohort with predominantly mild Coronavirus Disease 2019
(COVID-19). STUDY DESIGN: Hospital staff (n=94) returning to work
following polymerase chain reaction (PCR) confirmed COVID-19 were
offered antibody testing to assist with laboratory verification. Initial
specimens were collected at median 29 days post-symptom onset and run on
the Roche, Abbott, Siemens and DiaSorin platforms. Re-sampling occurred
at median 142 days from a subset of the initial cohort (n=62) that had
volunteered to provide further sera to assist in longitudinal
sensitivity analysis. Samples that were not run across all four
platforms were excluded from analysis. RESULTS: Comparative sensitivity
analysis was conducted on 89/94 of the initial specimens and 55/62 of
the repeat specimens. Sensitivity at initial sampling ranged from
78-87% across platforms. At re-sampling, sensitivities were: 100%
(Roche), 45% (Abbott), 100% (Siemens), and 80% (DiaSorin). Paired
analysis using the longitudinal cohort (n=55) demonstrated stable or
increasing median assay values on three platforms, with a clear
reduction seen only on the Abbott platform (4.78 to 1.34) with
corresponding sensitivity drop-off. CONCLUSION: The Abbott assay
demonstrated sensitivity drop-off and decrease in median assay signal
below detection threshold at 4-5 months. This has implications on the
interpretation and design of future studies