Global pneumococcal sequence cluster lineage for invasive pneumococcal isolates in Denmark from summer 2019 to 2023.

Denmark has monitored invasive pneumococcal diseases (IPD) for decades, observing shifts in serotype prevalence, partly due to pneumococcal conjugate vaccines in children. The COVID-19 pandemic and the Danish government's 2020 vaccination program with the 23-valent pneumococcal polysaccharide vaccine (PPV23) for older adults further influenced IPD epidemiology. This study explores the dynamics of Global Pneumococcal Sequence Clusters (GPSCs) in Denmark from 2019 to 2023 using whole-genome sequencing (WGS) on IPD isolates from all age groups received at Statens Serum Institut (SSI). Serotyping, multilocus sequence typing (MLST), GPSC identification, and phylogenetic analysis to assess clonal relationships were conducted. Of the 1,999 sequenced isolates, representing 93.3% of reported cases, 79 different GPSCs were identified, with GPSC3, GPSC12, and GPSC19 being dominant. GPSC3/ST53 (serotype 8) declined significantly from 24.6% in 2019 to 14.4% in 2023 (p < 0.05), whereas GPSC12/ST180 (serotype 3) increased significantly from 8.2% to 15.1% (p < 0.05). The PPV23 vaccine and pandemic restrictions decreased IPD incidence, particularly for vaccine-covered serotypes, yet serotype 3 remained problematic, indicating challenges in achieving broad serotype coverage. Although pneumococcal vaccination and pandemic-related public health measures influenced the distribution of serotypes and sequence types (STs), only two dominant GPSCs showed clear changes over time. This reflects that a single GPSC can encompass multiple serotype-ST combinations, including both vaccine-covered and non-vaccine variants. As a result, while GPSCs provide a useful high-level overview of pneumococcal lineages, they may lack the resolution needed to detect finer-scale shifts in serotype-ST composition, especially those critical for evaluating vaccine impact and identifying emerging clones.