Importance: A correlation between antibody levels and risk of infection has been demonstrated for the wild-type, Alpha, and Delta SARS-COV-2 variants. High rates of breakthrough infections by the Omicron variant emphasized the need to investigate whether the humoral response elicited by mRNA vaccines is also associated with reduced risk of Omicron infection and disease.

Objective: To investigate whether the high antibody levels in individuals who have received at least 3 doses of an mRNA vaccine are associated with reduced risk of Omicron infection and disease.

Design, setting, and participants: This prospective cohort study used serial real time-polymerase chain reaction (RT-PCR) and serological test data from January and May 2022 to assess the association of preinfection immunoglobin G (IgG) and neutralizing antibody titers with incidence of Omicron variant infection, incidence of symptomatic disease, and infectivity. Participants included health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. Data were analyzed from May to August 2022.

Exposures: Levels of SARS-CoV-2 anti-receptor binding domain IgG and neutralizing antibodies.

Main outcomes and measures: The main outcomes were incidence of Omicron infection, incidence of symptomatic disease, and infectivity. Outcomes were measured using SARS-COV-2 PCR and antigen testing and daily online surveys regarding symptomatic disease.

Results: This study included 3 cohorts for 3 different analyses: 2310 participants were included in the protection from infection analysis (4689 exposure events; median [IQR] age, 50 [40-60] years; 3590 [76.6%] among female health care workers), 667 participants (median [IQR] age, 46.28 (37.44,54.8); 516 [77.4%] female) in the symptomatic disease analysis, and 532 participants (median [IQR] age, 48 [39-56] years; 403 [75.8%] female) in the infectivity analysis. Lower odds of infection were observed for each 10-fold increase in preinfection IgG (odds ratio [OR], 0.71; 95% CI, 0.56-0.90) and for each 2-fold increase in neutralizing antibody titers (OR, 0.89; 95% CI, 0.83-0.95). The odds of substantial symptomatic disease were reduced for each 10-fold increase in IgG levels (OR, 0.48; 95% CI, 0.29-0.78) and for each 2-fold increase in neutralizing antibodies levels (OR, 0.86; 95% CI, 0.76-0.96). Infectivity, assessed by mean cycle threshold value, was not significantly decreased with increasing IgG or neutralizing antibodies titers.

Conclusions and relevance: In this cohort study of vaccinated health care workers, IgG and neutralizing antibody titer levels were associated with protection against infection with the Omicron variant and against symptomatic disease.

MayanGilboa,MD; TalGonen,MD; NoamBarda,MD,PhD; ShellyCohn,MD; VictoriaIndenbaum,PhD; YaelWeiss Ottolenghi,PhD; SharonAmit,MD,PhD; KerenAsraf,PhD; GiliJoseph,PhD; TalLevin,MSc; YaraKanaaneh,BSc; AlexAydenzon,BSc; MichalCanetti,MD; LaurenceFreedman,PhD; NetaZuckerman,PhD;  EllaMendelson,PhD; RamDoolman,PhD; YitshakKreiss,MD; GiliRegev Yochay,MD; YanivLustig,PhD