Longitudinal Comparison of Automated SARS-CoV-2 Serology Assays in Assessing Virus Neutralization Capacity in COVID-19 Convalescent Sera

Abstract

• Context.—Serologic tests on automated immunology analyzers are increasingly used to monitor acquired immunity against SARS-CoV-2. The heterogeneity of assays raises concerns about their diagnostic performance and comparability. Objective.—To test sera from formerly infected individuals for SARS-CoV-2 antibodies by using 6 automated serology assays and a pseudoneutralization test (PNT). Design.—Six SARS-CoV-2 serology assays were used to assess 954 samples collected during a 12-month period from 315 COVID-19 convalescents. The tests determined either antibodies against the viral nucleocapsid (anti-NC) or spike protein (anti-S). Two assays did not distinguish between antibody classes, whereas the others selectively measured immunoglobulin G (IgG) antibodies. PNT was used to detect the presence of neutralizing antibodies. Results.—Comparison of qualitative results showed only slight to moderate concordance between the assays (Cohen j, 0.57). Significant correlations (P, .001) were observed between the antibody titers from all quantitative assays. However, titer changes were not detected equally. A total anti-S assay measured an increase in 128 of 172 cases (74%) of a suitable subset, whereas all IgG anti-S tests reported decreases in at least 118 (69%). Regarding the PNT results, diagnostic sensitivities of 89% or greater were achieved with positive predictive values of at least 93%. In contrast, specificity changed substantially over time, varying from 20% to 100%. Conclusions.—Comparability of serologic SARS-CoV-2 antibody tests is rather poor. Owing to different diagnostic specificities, the tested assays were not equally capable of capturing changes in antibody titers. However, with thoroughly validated cutoffs, IgG-selective anti-S assays are a reliable surrogate test for SARS-CoV-2 neutralizing antibodies in former COVID-19 patients.