Cell-Mediated Immunity (CMI) for SARS-CoV-2 Infection Among the General Population of North India: A Cross-Sectional Analysis From a Sub-sample of a Large Sero-Epidemiological Study

Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination.Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-gamma) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-gamma ELISpot) assay was carried out to determine the levels of virus-specific IFN-gamma producing cells in individual samples.Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-gamma response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-gamma producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status.Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated.