Comparison of anti‐nucleocapsid antibody assays for the detection of SARS‐CoV‐2 Omicron vaccine breakthroughs after various intervals since the infection

Abstract

AbstractAntibody assays with the nucleocapsid (NC) protein as the target antigen can identify severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections when polymerase chain reaction (PCR) analyses are unavailable. Regarding the kinetics of NC‐specific antibodies, vaccine breakthroughs with Omicron subvariants may differ from infections with the ancestral wild‐type virus. Therefore, we evaluated which assays have the highest sensitivity for detecting NC‐specific antibodies after various intervals since breakthrough infections with an Omicron subvariant. The study included 279 samples from vaccinated subjects who experienced PCR‐confirmed Omicron breakthrough infections between 21 and 266 days before sampling. The samples were comparatively assessed with the Elecsys® Anti‐SARS‐CoV‐2 N (Roche), the Anti‐SARS‐CoV‐2‐NCP‐ELISA (Euroimmun), the recomLine SARS‐CoV‐2 IgG (Mikrogen), and the SARS‐CoV‐2 ViraChip IgG assays (Viramed). In the whole cohort, the Elecsys® Anti‐SARS‐CoV‐2 N assay displayed the highest sensitivity (93%, p < 0.0001), followed by the recomLine SARS‐CoV‐2 IgG assay (70%), the SARS‐CoV‐2 ViraChip IgG assay (41%) and the Anti‐SARS‐CoV‐2‐NCP‐ELISA (35%). Although measured antibody levels and time‐dependent sensitivities differed, the extent of the antibody decrease was similar among all assays. As demonstrated by this study, manufacturer‐dependent differences in the sensitivities of NC‐specific antibody assays should be considered when serology is applied to link previous SARS‐CoV‐2 infections with potential post‐COVID sequelae.