Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009–2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27–0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.

A hypothetical influenza infection-induced non-specific immunity may reduce the risk of subsequent non-influenza respiratory virus (NIRV) infection and bias the influenza vaccine effectiveness (VE) estimates in test-negative designs (TNDs). We conducted a simulation study using a simple TND model and explored the degree of bias in the VE estimates. The bias was marginal during the usual seasons and most of the time during pandemics; the bias only became large when the influenza infection attack rate increased to pandemic levels (>50%), the true VE was low to moderate, and the non-specific immunity almost completely protected from NIRV infections and lasted at least half the influenza season.