No abstract

The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal transmission of the bacteria.

Introduction While secondary pneumococcal pneumonia occurs less commonly after COVID-19 than after other viral infections, it remains unclear whether other interactions occur between SARS-CoV-2 and Streptococcus pneumoniae. Methods We probed potential interactions between these pathogens among adults aged ≥65y by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate and 23-valent polysaccharide; PCV13, PPSV23). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly-robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci. Results Among 531,033 adults, there were 3,677 COVID-19 diagnoses, leading to 1,075 hospitalizations and 334 fatalities, between 1 March-22 July, 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval: 0.59-0.72), 0.68 (0.57-0.83), and 0.68 (0.49-0.95), respectively. Prior PPSV23 receipt was not associated with protection against the three outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (0.50-0.84) and 0.62 (0.56-0.70) during risk periods 91-365d and >365d following antibiotic receipt, respectively. Discussion Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests pneumococci may interact with SARS-CoV-2.

Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence.

The use of pneumococcal conjugate vaccines (PCVs) in children has a strong indirect effect on disease rates in adults. When children are vaccinated with PCVs, other serotypes that are not targeted by the vaccine can increase in frequency (serotype replacement) and reduce the direct and indirect benefits of the vaccine. To understand and predict the likely impacts of serotype replacement, it is important to know how patterns in the transmission of serotypes among children relate to disease rates in adults. We used data on pneumococcal carriage and disease from Navajo Nation children and adults collected before and after the routine use of PCVs (1998-2012). Using regression models within a Bayesian framework, we found that serotype-specific carriage and invasiveness (disease incidence divided by carriage prevalence) had similar patterns in children and adults. Moreover, carriage in children, invasiveness in children, and a serotype-specific random intercept (which captured additional variation associated with the serotypes) could predict the incidence serotype-specific pneumococcal disease in adults 18-39 years of age and those 40 years of age or older in the era of routine use of PCVs. These models could help us predict the effects of future pneumococcal vaccine use in children on disease rates in adults, and the modeling approach developed here could be used to test these findings in other settings.