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

Abstract

Context.– Serological tests on automated immunology analyzers are increasingly used to monitor the 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 utilizing six automated serology assays and a pseudoneutralization test (PNT). Design.– Six SARS-CoV-2 serology assays were utilized to assess 954 samples collected during a 12 months 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 immunoglubulins 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's kappa < 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 out 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 ≥89% were achieved with PPVs ≥93%. In contrast, specificity changed substantially over time varying from 20 to 100%. Conclusions.– Comparability of serological SARS-CoV-2 antibody tests is rather poor. Due to different diagnostic specificities, the tested assays were not equally capable of capturing changes in antibody titers. However, with thoroughly validated cut-offs, IgG-selective anti-S assays are a reliable surrogate test for SARS-CoV-2 neutralizing antibodies in former COVID-19 patients.

Development of a Rapid Live SARS-CoV-2 Neutralization Assay Based on a qPCR Readout

“…The 69 convalescent-phase sera used in this study (Convalescent Cohort [5003_20]) were obtained from nonhospitalized volunteers (median age = 42 years; range: 21–80) with confirmed COVID-19 infections between March 2020 and January 2021 ( 11 , 33 ). For cross-neutralization against the Alpha and Beta variants, we exclusively used sera before the emergence of the Alpha and Beta variants in Austria (COVID-19 diagnosis before November 2020).…”

“…Although rapid ELISA-based methods exist ( 11 ), they are usually designed for one single virus variant, and most importantly, they only determine the ability of antibodies to bind to viral structures and do not measure functional antiviral responses. Several modified ELISA techniques have been developed recently ( 12 – 14 ) that detect antibodies that interfere in the interaction between the viral receptor binding domain (RBD) and the human host receptor, human angiotensin-converting enzyme-2.…”

HIV HGM biobank as a research platform for paediatric infectious diseases and COVID-19 pandemic

“…[ 19 , 20 ]. This biobank represents a novel approach, not only to HIV-1 infection, but also to a COVID-19 research, and specializes in paediatric population [ 21 – 25 ]. This is why the HIV HGM BioBank is of general interest to basic and clinical research teams working on HIV-1 and COVID-19, and also to those groups who try to establish large networks focused on research on specific clinical problems in epidemiology, biology, routes of transmission and potential therapies [ 26 ].…”