Anti‐Spike IgG antibodies as correlates of protection against SARS‐CoV‐2 infection in the pre‐Omicron and Omicron era

Abstract

AbstractAnti‐Spike IgG antibodies against SARS‐CoV‐2, which are elicited by vaccination and infection, are correlates of protection against infection with pre‐Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti‐Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS‐CoV‐2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS‐CoV‐2 infection ascertained by self‐report or seroconversion of anti‐Nucleocapsid antibodies. At the time of their earliest available anti‐Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8–55.2), with 45.3% being female, 41.3% having a prior SARS‐CoV‐2 infection, and 75.5% having received at least one dose of a COVID‐19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS‐CoV‐2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7–12.4). The age‐ and sex‐adjusted hazard ratio for SARS‐CoV‐2 associated with having twice the anti‐Spike IgG antibody titer was 0.875 (95% credible interval 0.868–0.881) overall, 0.842 (0.827–0.856) during 2021, and 0.884 (0.877–0.891) during 2022 (all p < 0.001). The associations were similar in females and males (Pinteraction = 0.673) and across age (Pinteraction = 0.590). Higher anti‐Spike IgG antibody titers were associated with reduced risk of incident SARS‐CoV‐2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti‐Spike IgG antibody continues to be a suitable correlate of protection against newer SARS‐CoV‐2 variants.