Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study

Background Identifying COVID-19 correlates of protection and immunity thresholds is important for policy makers
and vaccine development. We aimed to identify correlates of protection of BNT162b2 (Pfizer–BioNTech) vaccination
against COVID-19.

Methods In this prospective cohort study, households within a radius of 40 km of the Sheba Medical Center in Israel
in which a new SARS-CoV-2 infection (defined as the index case) was detected within the previous 24 h were
approached between July 25 and Nov 15, 2021. We included adults (aged >18 years) who had received one or two
vaccine doses, had an initial negative SARS-CoV-2 PCR and no previous infection reported, and had a valid IgG and
neutralising antibody result. The exposure of interest was baseline immune status, including IgG antibody
concentration, neutralising antibody titre, and T-cell activation. The outcomes of interest were PCR-positive SARSCoV-
2 infection between day 2 and day 21 of follow-up and intensity of disease symptoms (self-reported via a telephone
questionnaire) among participants who had a confirmed infection. Multivariable logistic and ordered logit ordinal
regressions were used for the adjusted analysis. To identify immunological thresholds for clinical protection, we
estimated the conditional probability of infection and moderate or severe disease for individuals with pre-exposure
IgG and neutralising antibody concentrations above each value observed in the study data.