Clinical and population genomic epidemiology of invasive group A streptococcus in Scotland, 2014-2024

Abstract Objectives: Following the COVID-19 pandemic, multiple countries reported a surge in invasive group A streptococcus (iGAS) infections. Posited explanations include reduced population immunity, increased respiratory virus co-infection, and emergence of hypervirulent GAS clones. To assess the relative contribution of these factors, we analyzed the epidemiology and genomics of 3,408 iGAS infections in Scotland. Methods: National surveillance data from 2014-2024 were analyzed to characterize iGAS incidence. Hybrid whole genome sequencing was used to comprehensively genetically characterize 404 emm1 isolates collected from invasive and tonsillitis infections. Results: iGAS incidence markedly increased in late 2022 and early 2023, disproportionately affecting children and older adults. This surge was not associated with a proportional increase in bacteremia but did coincide with increased influenza and respiratory syncytial virus infections. Genomic analyses found that emm1 post-pandemic isolates were not genetically distinct from pre-pandemic isolates in genome-wide polymorphisms, accessory genes including virulence and antimicrobial resistance determinants, mobile genetic elements, or chromosomal structural variants. Conclusions: The post-pandemic iGAS surge in Scotland was not associated with emergence of a novel hypervirulent emm1 clone. Instead, the epidemiologic and population genomic findings are consistent with increased host susceptibility following reduced pathogen exposure during the pandemic and increased respiratory virus co-infection as predominant contributing factors.