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

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 antispike 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Institutional Ethics Committee of the AIG Hospitals (AIG/IEC-BH&R 54/12.2023-01). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors