Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014

Abstract

Abstract 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.