Our study has several important limitations. First, as the Delta variant was the dominant strain in Israel during the study period, the observed decrease in long-term protection afforded by the vaccine against other strains cannot be inferred. Second, we did not measure the effect of vaccination time on symptomatic infection, severe disease or hospitalization. Lastly, the results might be affected by differences between the groups in terms of health behaviors (such as social distancing and mask-wearing), a possible confounder that was not assessed. As chronically-ill patients were given priority for vaccination, confounding by indication should be considered when interpreting the study results; nonetheless, adjusting for obesity, cardiovascular disease, diabetes, hypertension, chronic kidney disease, cancer, COPD, IBD and immunosuppression had only a small impact on the estimate of effect as compared to the unadjusted OR. Therefore, residual confounding by unmeasured facotrs is unlikely.
Taken together, the study suggests a possible relative decrease in the long-term protection of the BNT162b2 vaccine against the Delta variant of SARS-CoV-2. This preliminary finding should be evaluated in future studies, including a comparison to long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.