Mortality Among Patients With Invasive Group A Streptococcal Infections Caused by the M1UK Lineage: A Retrospective Cohort Study in England and Wales.

BACKGROUND: The M1UK sublineage of Streptococcus pyogenes has driven recent post-pandemic surges in invasive group A streptococcal (iGAS) disease. We assessed case fatality rate (CFR) among patients with emm1 iGAS in England and Wales, and then compared outcomes associated with M1UK and ancestral emm1 lineages. METHODS: We linked emm1 iGAS cases (December 2009-July 2022) with demographic and mortality records. Lineage was determined for isolates collected in 2010, 2013-2016, and 2020 via whole-genome sequencing or allele-specific PCR. Seven- and 30-day all-cause CFRs were estimated. Univariate and multivariate models assessed the association between lineage and risk of death. RESULTS: Among 4952 emm1 iGAS cases, lineage was assigned to 1356. The 30-day CFR was 24.4% for M1UK, 22.3% for M1global, 10.5% for M123SNP, and 10.3% for M113SNP. After adjustment for age and sex, lineage was not a significant predictor of 7- or 30-day mortality. Survival analysis showed rapid progression to death in both M1UK and M1global cases: 63.7% of deaths occurred within 1 day of diagnostic sampling. Among children under 15 years, 56.3% of fatal cases died before sampling, and 95.6% within 1 day of sampling. CONCLUSIONS: Mortality did not differ significantly between M1UK and M1global lineages, but more studies are required. Overall mortality from emm1 S. pyogenes remains strikingly high. The rapid time to death underscores the need for preventive measures and rapid diagnostic tools that act prior to culture-based confirmation, and highlights challenges for clinical trial design in iGAS.