Evidence for cross-protection against subsequent febrile respiratory illness episodes from prior infections by different viruses among Singapore military recruits 2009-2014

Background: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). Methods: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. Results: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14–.44) or influenza virus (HR, 0.52; 95% CI, .38–.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062–.093), while men with influenza virus–positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). Conclusion: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.Ministry of Defence (MINDEF)Ministry of Education (MOE)Published versionThis work was supported by the Ministry of Education (tier 1 grant R-608-000-132-112 to C. X. P. C.) and by the Centre for Infectious Disease Epidemiology and Research, Saw Swee Hock School of Public Health (funded by the Singapore Ministry of Defence)