Objective Animal and in vitro studies suggest that viral acute respiratory infection (VARI) can predispose to pneumococcal infection. These findings suggest that the prevention of VARI can yield additional benefits for the control of pneumococcal disease (PD). In population-based studies, however, the evidence is not in accordance, possibly due to a variety of methodological challenges and problems in these studies. We aimed to summarise and critically review the methods and results from these studies in order to inform future studies.

Methods We conducted a systematic review of population-based studies that analysed the association between preceding seasonal VARI and subsequent PD. We searched MEDLINE, Embase and Global Health databases using tailored search strategies.

Results A total of 28 studies were included. After critically reviewing the methodologies and findings, 11 studies did not control for seasonal factors shared by VARI and PD. This, in turn, could lead to an overestimation of the association between the two illnesses. One case–control study was limited by its small sample size (n case=13). The remaining 16 studies that controlled for seasonal factors suggested that influenza and/or respiratory syncytial virus (RSV) infections were likely to be associated with the subsequent occurrence of PD (influenza: 12/14 studies; RSV: 4/5 studies). However, these 16 studies were unable to conduct individual patient data-based analyses. Nevertheless, these studies suggested the association between VARI and subsequent PD was related to additional factors such as virus type and subtype, age group, comorbidity status, presentation of PD and pneumococcal serotype.

Conclusions Population-based studies do not give consistent support for an association between preceding seasonal VARI and subsequent PD incidence. The main methodological challenges of existing studies include the failure to use individual patient data, control for seasonal factors of VARI and PD, or include other factors related to the association (eg, virus, age, comorbidity and pneumococcal serotype).