Modelling COVID-19 Vaccine Breakthrough Infections in Highly Vaccinated Israel-The Effects of Waning Immunity and Third Vaccination Dose

In August 2021, a major wave of the SARS-CoV-2 Delta variant erupted in the highly vaccinated population of Israel. The transmission advantage of the Delta variant enabled it to replace the Alpha variant in approximately two months. The outbreak led to an unexpectedly large proportion of breakthrough infections (BTI)-a phenomenon that received worldwide attention. Most of the Israeli population, especially those aged 60+, received their second dose of the vaccination four months before the invasion of the Delta variant. Hence, either the vaccine induced immunity dropped significantly or the Delta variant possesses immunity escaping abilities, or both. In this work, we model data obtained from the Israeli Ministry of Health, to help understand the epidemiological factors involved in the outbreak. We propose a mathematical model that captures a multitude of factors, including age structure, the time varying vaccine efficacy, time varying transmission rate, BTIs, reduced susceptibility and infectivity of vaccinated individuals, protection duration of the vaccine induced immunity, and the vaccine distribution. We fitted our model to COVID-19 cases among the vaccinated and unvaccinated, for <60 and 60+ age groups, and quantified the transmission rate, the vaccine efficacy over time and the impact of the third dose booster vaccine. The peak transmission rate of the Delta variant was found to be 2.14 times higher than that of the Alpha variant. The two-dose vaccine efficacy against infection dropped significantly from >90% to ∼40% over 6 months. We further performed model simulations and quantified counterfactual scenarios examining what would happen if the booster had not been rolled out. We estimated that approximately 4.03 million infective cases (95%CI 3.19, 4.86) were prevented by vaccination overall, and 1.22 million infective cases (95%CI 0.89, 1.62) averted by the booster.