Background Invasive pneumococcal disease (IPD) is influenced by vaccination strategies, circulating serotypes and respiratory viral activity. The COVID-19 pandemic substantially altered respiratory infection dynamics. The aim of the study was to evaluate temporal changes in IPD incidence, clinical characteristics and serotype distribution before, during and after the COVID-19 pandemic. Methods We conducted a retrospective study of all IPD cases diagnosed between January 2018 and December 2023 at a tertiary hospital in Madrid, Spain. IPD was defined by isolation or molecular detection of Streptococcus pneumoniae from normally sterile sites. Demographic, clinical, microbiological and virological data were analysed, together with available respiratory viral testing results, although testing was not systematic and viral coinfections may have been underdetected. Incidence rates were calculated using the hospital catchment population. Temporal patterns of IPD and population-level respiratory virus detections were compared descriptively. Results A total of 315 patients were identified, including 256 adults (81.3%) and 59 children (18.7%). Pneumonia was the most frequent clinical presentation (76.5%). Adults had a higher prevalence of comorbidities (78.1%) and mortality (11.3%), whereas children were generally healthy and more frequently required intensive care (67.8%), largely due to empyema-related management rather than increased disease severity. Overall, 68.6% of isolates were serotyped; serotypes 8 and 3 predominated. The annualized incidence of IPD decreased from 15.4 cases per 100,000 inhabitants (95% CI, 13.0–18.0) before the pandemic to 6.7 (95% CI, 5.5–8.2) during the pandemic period, followed by a partial recovery to 10.8 (95% CI, 7.4–15.1) in the post-pandemic period. Incidence calculations were restricted to patients residing within the hospital catchment area ( n = 284). Respiratory viral coinfection was documented in 18.4% of cases and was more frequent in children (39%). Serotype 11A showed the highest proportion of penicillin resistance. Conclusion IPD incidence declined sharply during the pandemic and increased again thereafter, coinciding with substantial changes in respiratory virus circulation. The persistent circulation of serotype 3 and the emergence of non-vaccine serotypes underscore the need for continued surveillance and updated vaccination strategies.
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