Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis

Abstract

Abstract Background Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development. Methods We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti–receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID. Results Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%–77%) and 72% (95% CI, 53%–83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID. Conclusions Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID.