Abstract

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with increased long-term mortality, but it is unclear if this is explained by pre-existing comorbidities. We aimed to estimate the long-term survival following IPD in comparison with the general population, adjusting for potential confounders such as underlying comorbidities. METHODS: We conducted a matched cohort study comparing long-term survival (>120 days after infection) in individuals with IPD and comparators without IPD. Cases were individuals aged 65 years or older with laboratory-confirmed IPD (2012-19) identified through enhanced national surveillance. Comparators matched on age, sex, and calendar date of laboratory-confirmed diagnosis were drawn from primary care electronic health records in Clinical Practice Research Datalink GOLD. We used Cox regression, stratified by matched set, to compare mortality in people with and without IPD, adjusting for relevant comorbidities, socioeconomic deprivation, and ethnicity. FINDINGS: We included 13 401 IPD cases and 67 005 comparators without IPD. There were 5038 (53·5%) female and 4380 (46·5%) male IPD cases and 19 927 (53·5%) female and 17 351 (46·5%) male comparators without IPD. After adjusting for comorbidities, socioeconomic deprivation, and ethnicity, we found increased all-cause mortality in IPD cases compared with comparators without IPD (hazard ratio 3·74 [95% CI 3·50-3·99]). The predicted median survival was 4·7 years (IQR 2·9-7·4) for IPD cases and more than 11·9 years (IQR 8·7 to >11·9) for comparators without IPD. This increased mortality was consistent across subgroups defined by age, vaccination history, and comorbidity status (including diabetes, chronic respiratory disease, and chronic heart disease). INTERPRETATION: IPD was associated with increased mortality at least 5 years after infection. These findings emphasise the value of IPD prevention and the need for more research into the clinical management of people who have had IPD. Long-term mortality should be incorporated in cost-effectiveness analyses for pneumococcal vaccines. FUNDING: National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation (NIHR200929).