COVID-19 vaccination-infection status and immunological profile from India: A case study for prioritizing at risk population for targeted immunization.

Abstract

The COVID-19 pandemic's global impact was mitigated through rapid vaccine development, leading to a mix of natural and vaccination-derived immunity. The immunological profile in hybrid immunity remains less studied, especially in regions where non-mRNA vaccines were used. This study focuses on the immunological profiles and predictors of immune response in one such population. This cohort study assessed their humoral and cellular immune responses, breakthrough Omicron infections, and hospitalization rates based on vaccination and infection history. Immunological assays to measure anti-spike protein and neutralizing antibodies and interferon-γ release assay were performed. Regression models were used to estimate predictors of immune response and hospitalization in patients with breakthrough infections. The study revealed significant differences in immune response among participants based on their hybrid immunity status, vaccination, and infection history. Higher antibody titers and cellular responses were observed in individuals with hybrid immunity, especially those with dual pre-Omicron and Omicron infections (3326 BAU/ml, IQR: 770.25-5678.25 and 4.92 IU of IFN-γ/mL, respectively, <i>P</i> < 0.001). Age, hypertension, baseline antibody levels, and vaccination status were found to predict humoral response. Baseline antibody levels were found to be predictive of hospitalization, and no participants with an antibody titer >250 BAU/mL required hospitalization. Hybrid immunity is linked to a stronger humoral and cellular immune response, and elevated antibody titers can serve as a surrogate marker for protection against hospitalization. These findings highlight the need to prioritize high-risk groups, such as older adults and individuals with comorbidities, for booster vaccinations to strengthen community-level defenses against COVID-19.