ABSTRACT
Background: The COVID-19 pandemic's global impact was mitigated through rapid vaccine development, leading to a mix of natural and vaccination-derived immunity. Immunological profile in hybrid immunity remains less studies, 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. Methods: This was a cross-sectional study to assess their humoral and cellular immune responses based on vaccination and infection history. Immunological assays were performed to measure anti-spike protein and neutralizing antibodies as well as interferon-γ release assay. Multivariable linear regression model was used to estimate predictors of immune response. Results: The study revealed significant differences in immune response among participants based on their hybrid immunity status, vaccination, and infection history. Higher antibody titres 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, IQR:3.74-16.98 respectively, p <0.001). Age and comorbidities such as diabetes and hypertension were associated with lower antibody levels and cellular response, while vaccination and hybrid immunity correlated with higher immune responses. Conclusion: The prevalence of hybrid immunity was high, yet a substantial portion of the population lacks it, indicating the necessity for targeted immunization strategies. The findings underscore the importance of prioritizing high-risk individuals, such as elderly and individuals with comorbidities, for booster vaccinations to enhance community-level protection against COVID-19.