Post-pandemic upsurge in Group A Streptococcus infections at an Italian tertiary university hospital

Streptococcus pyogenes (Group A Streptococcus; GAS) is a pathogen of global significance. In the pre-antibiotic era, GAS was a major cause of childhood morbidity and mortality, but its spread rapidly declined until the mid-2010s. The continuing increase in GAS infections, associated with the expansion of the M1(UK) lineage, was observed first in the United Kingdom (UK) and, later, globally. Here, we endeavor to assess the various determinants underlying the post-pandemic GAS upsurge, with a focus on microbial genomic features. We performed an epidemiological analysis of all laboratory-confirmed GAS infections identified between June 2018 and June 2024 at a tertiary University Hospital located in Northern Italy, dividing them into three levels of severity: mild, moderate, and invasive GAS infections. A subset of 34 representative GAS isolates identified in the post-pandemic period were subjected to short- and long-read whole genome sequencing (WGS). Of the 531 GAS cases analyzed during this period, the majority (415, 78.2%) occurred in the last two years. This increase in GAS cases correlated with a significant shift in infection severity: among the 118 GAS cases identified in the June 2018-May 2022 period, only one resulted in an invasive infection (1/118, 0.8%). In contrast, among the 531 GAS cases identified in the June 2022-May 2024 period, 32 caused invasive infections (32/531, 7.9%). WGS of 34 isolates (including 15 invasive isolates) identified 11 different emm types, the most frequent being emm1 (9 isolates) followed by emm12 (7 isolates), then emm89 and emm28 (4 isolates each). Among the emm1 isolates, the M1(UK) sublineage was the most represented (8 out of 9 isolates), with the remaining "singleton" belonging to the M1(13SNP) sublineage.