RSV and Rhinovirus asymptomatic upper airway infection increases pneumococcal carriage acquisition rates and density in adults whereas nasal inflammation is associated with bacterial shedding

Nasopharyngeal pneumococcal colonization is a necessary step for disease development and the primary reservoir of bacterial spread and transmission. Most epidemiological studies report the impact of co-infection with respiratory viruses upon disease rates and outcome, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we used controlled human infection with pneumococcus to assess whether certain respiratory viruses alter susceptibility to pneumococcal colonization and bacterial density. A total of 581 healthy adults were screened for presence of upper respiratory tract viral infection before intranasal pneumococcal challenge. We showed that RSV and Rhinovirus asymptomatic infection conferred a substantial increase in carriage rates (88% and 66% of colonized individuals in Rhinovirus and RSV infected groups, respectively, vs 49% in the virus negative group). The risk ratio of pneumococcal colonization in RSV infected group was 5.3 (95% CI: 0.90 - 30.61, p = 0.034) and 2.03 (95% CI: 1.09-3.80, p= 0.035) in rhinovirus infected group. Pneumococcal density was overall greater in virus positive subjects, although RSV infection alone had a major impact on pneumococcal density up to 9 days post challenge, with a substantial 2-log increase at D2 compared to virus negative group (median, SEM: 3.76 +/- 0.65 vs 1.79 +/- 0.09) (p= 0.02). We also studied rates and kinetics of bacterial shedding through the nose and oral route in a subset of challenged individuals. Nasal bacterial shedding was twice more frequent than cough-induced shedding (64% vs 32%, respectively). High levels of bacterial colonization density and nasal inflammation were strongly correlated with increased odds of nasal shedding, as opposed to cough-shedding. Healthy adults can act as reservoirs of transmission for pneumococcus, particularly when colonized with high density and have local inflammation, two key characteristics of pneumococcal colonization in pediatrics and/or viral co-infection. Hence, vaccines targeting these respiratory pathogens have the dual potential of reducing transmission and disease burden due to their indirect benefit to off-target pathogens.