Previous studies have reported an association between antibody titers and protection from infection
with SARS-CoV-2 at both the individual and population level.1-3 However, those studies were
conducted before the emergence of the highly infectious Omicron variant of concern (VOC), and
enrolled individuals who were vaccinated with 2 vaccine doses, before a third vaccine dose was
widely recommended.

The Omicron VOC emerged in Israel in late 2021, along with thewaning of the humoral response
that followed the third vaccine dose.4 The dramatic increase in breakthrough infections among
vaccinated individuals drove decision-makers in Israel to recommend the administration of a fourth
BNT162b2 (Pfizer/BioNTech) vaccine dose to health care workers (HCWs) and other populations
considered at high risk, such as older adults and people with immune disorders. This vaccination
campaign was associated with protection against mortality and hospitalizations among those
vaccinated.5 However, the efficacy against infection was not as marked as it was found to be for
previous doses,6 and the appropriate timing of the fourth dose in the general population
remained unknown.

In this study, we investigated whether humoral immunity can serve as a biomarker associated
with protection against infection and symptomatic disease from SARS-CoV-2 Omicron VOC, at a time
when the BA.1 and BA.2 lineages were the most predominate infections in Israel. Specifically, we
explore the association of an individual’s preinfection titers of antispike immunoglobin G (IgG) and
neutralizing antibodies with 3 different outcomes: SARS-CoV-2 infection (as confirmed by
polymerase chain reaction [PCR] testing), symptomatic disease, and infectivity among those