Hybrid immunity against SARS‑CoV‑2: Mechanisms, duration and global implications (Review)

Since the commencement of the coronavirus disease 2019 (COVID‑19) pandemic, understanding the nature and durability of immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has been central to public health strategies. Emerging evidence indicates that the combination of prior infection and vaccination, termed hybrid immunity, provides superior protection compared to infection‑ or vaccine‑induced immunity alone. The present review synthesizes currently available evidence on the mechanisms, durability and global implications of hybrid immunity, emphasizing its relevance for vaccination strategies, pandemic preparedness and health equity. The present review conducted a narrative synthesis of peer‑reviewed studies, systematic reviews and meta‑analyses published between 2020 and 2023, focusing on immunological mechanisms, epidemiological outcomes and policy implications of hybrid immunity. Mechanistically, it has been demonstrated that hybrid immunity elicits broader and more potent neutralizing antibodies, enhances memory B‑cell diversity and supports cross‑reactive T‑cell responses across variants of concern. Epidemiological evidence indicates that hybrid immunity confers the highest protection against infection, severe disease, hospitalization and mortality. Protection against reinfection wanes over time, particularly against immune‑evasive Omicron subvariants, although protection against severe outcomes remains durable for at least 6‑12 months. Booster vaccination further strengthens hybrid immunity. However, due to global disparities in vaccine access, individuals in high‑income regions disproportionately benefit from hybrid immunity, while populations in low‑ and middle‑income countries often rely on infection‑derived immunity alone. Hybrid immunity represents the most resilient form of protection against COVID‑19, combining the advantages of both natural and vaccine‑induced immunity. Its superior breadth and durability have critical implications for vaccination policies, particularly regarding booster prioritization and the development of variant‑proof vaccines. Ensuring equitable access to vaccines remains essential to maximize the protective benefits of hybrid immunity worldwide and to strengthen preparedness against future pandemics.