Protection and waning of vaccine-induced, natural and hybrid immunity to SARS-CoV-2 in Hong Kong

Background: As the COVID-19 pandemic transitions into its fourth year, understanding the dynamics of immunity is critical for implementing effective public health measures. This study examines vaccine-induced, natural, and hybrid immunity to SARS-CoV-2 in Hong Kong, focusing on their protective effectiveness and waning characteristics against infection during the Omicron BA.1/2 dominant period. Research Design and Methods: We conducted a territory-wide retrospective cohort study using vaccination and infection records from the Hong Kong Department of Health. The analysis included over 6.5 million adults, applying the Andersen-Gill model to estimate protective effectiveness while addressing selection bias through inverse probability weighting. Results: Vaccine-induced immunity peaked one month after the first dose but waned rapidly, while boosters significantly prolonged protection. Infection-induced immunity showed higher initial effectiveness but declined faster than vaccine-induced immunity. Hybrid immunity provided the most durable protection. mRNA vaccines (Comirnaty) demonstrated greater effectiveness and slower waning compared to inactivated vaccines (CoronaVac). Conclusions: Hybrid immunity represents the most effective strategy for sustained protection against SARS-CoV-2. Public health policies should emphasize booster campaigns and hybrid immunity pathways to enhance population-level immunity and guide future COVID-19 management in Hong Kong.