Superior magnitude and durability of hybrid immunity following SARS-CoV-2 infection.

BACKGROUND

The emergence of the SARS-CoV-2 Delta variant necessitated examining hybrid immunity (vaccination- plus-infection) to optimize boosting strategies. We analyzed the kinetics, magnitude, and durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) following Delta infection.

OBJECTIVE

This study analyzed the kinetics, magnitude, and long-term durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) levels following Delta variant infection across individuals with diverse vaccination histories.

METHODS

This observational cohort study monitored 161 patients with varying vaccination histories for up to 16 weeks post-infection. Responses were compared against SARS-CoV-2 naïve controls receiving a two-dose inactivated series plus a heterologous booster. Sub-analyses assessed post-infection booster immunogenicity.

RESULTS

Prior vaccination significantly enhanced humoral responses. Patients with two prior doses achieved the highest median Anti-sRBD IgG peaks, surpassing vaccine-boosted naïve controls. While unvaccinated individuals exhibited delayed primary responses, hybrid immunity demonstrated superior durability with slower antibody decay than vaccine-only immunity. Crucially, while a post-infection booster effectively primed unvaccinated patients, early boosting in previously vaccinated individuals yielded minimal immunological gain.

CONCLUSIONS

Prior vaccination significantly enhanced humoral responses. Patients with two prior doses achieved the highest median Anti-sRBD IgG peaks, surpassing vaccine-boosted naïve controls. While unvaccinated individuals exhibited delayed primary responses, hybrid immunity demonstrated superior durability with slower antibody decay than vaccine-only immunity. Crucially, while a post-infection booster effectively primed unvaccinated patients, early boosting in previously vaccinated individuals yielded minimal immunological gain.