Systemic Innate Immune Mediators and Their Associations with Clinical Manifestations, Viral Coinfection and Prior Vaccination in Infants Hospitalized with Pertussis

Systemic innate immune responses during infant pertussis remain incompletely characterized, particularly in relation to disease severity, vaccination and respiratory viral coinfection. We conducted a prospective observational study of 61 infants younger than 12 months hospitalized with PCR-confirmed pertussis. Seven serum cytokines and chemokines were measured during early hospitalization, and their associations with clinical manifestations, vaccination and viral coinfection were investigated. Correlation analysis and principal component analysis identified a coordinated pro-inflammatory cluster comprising IL-1β, TNF-α, IL-6, IL-8 and CCL3 (PC1), and a distinct component mainly reflecting CXCL10 and IL-10 (PC2). No individual cytokine or composite profile was significantly associated with clinical manifestations after correction for multiple comparisons, although exploratory associations of CXCL10 and PC2 with respiratory distress were observed. Respiratory viral coinfection was independently associated with higher CXCL10 concentrations (2.21-fold increase; 95% CI 1.28–3.82; p = 0.0045; FDR q = 0.032). Prior vaccination and respiratory viral coinfection showed opposite trends in their associations with inflammatory mediators, with vaccination tending to be associated with stronger pro-inflammatory responses. Previously vaccinated infants also had higher anti-pertussis toxin IgG concentrations (p = 0.0006). These findings highlight distinct patterns of systemic immune activation during infant pertussis, influenced by respiratory viral detection and prior immune history, without clear associations with clinical severity.