Comorbidity-associated reduction in humoral and cellular immunity to respiratory syncytial virus in older adults at a tertiary care setting in India

Older adults with comorbidities experience substantial morbidity from respiratory syncytial virus (RSV), yet evidence from low- and middle-income countries on functional RSV immunity, particularly the relationship between humoral and cellular immune responses remain limited. We conducted a cross-sectional study among adults aged ≥ 60 years at a tertiary care center in New Delhi, India. Individuals attending outpatient clinics or admitted for non-acute, non-respiratory conditions were eligible. Enrolled individuals were found to be RSV seropositive in all age groups. Binding antibody levels varied widely but did not differ by age or sex. The magnitude of neutralizing antibody titers was lower in older adults with comorbidities compared to young healthy adults and we found a positive correlation between binding IgG and neutralizing antibody titers. Neutralizing activity was significantly lower in older adults with chronic liver disease ( p = 0·009) and malignancy ( p = 0·04). On multivariable analysis, chronic liver disease (aOR 7·83), malignancy (aOR 4·12), and diabetes (aOR 2·98) were independently associated with lower neutralization. RSV-specific T-cell responses were significantly lower in older adults than in healthy young adults, with median IFN-γ ELISpot values of 8 and 68 spot-forming units (SFU) per million cells, respectively ( p = 0·0068). Majority of the samples from older adults failed to produce IL-2, IFN-γ or TNF-α in CD4 + /CD8 + cells upon stimulation with RSV peptide pool. Despite comparable levels of RSV-F binding antibodies, older adults with comorbidities had significantly lower levels of RSV-neutralizing antibodies and RSV-specific T-cell responses.