Mortality among patients with invasive group A streptococcal infections caused by the M1 UK lineage: a retrospective cohort study in England and Wales
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
The M1 UK sublineage of S. pyogenes has dominated post-pandemic upsurges in invasive group A streptococcal (iGAS) disease. Using a national cohort of patients with emm 1 iGAS infections, we compared the case fatality rate (CFR) attributable to M1 UK with ancestral emm 1 lineages.
Methods
We linked emm 1 S. pyogenes iGAS cases in England and Wales between December 2009-July 2022 to demographic and mortality data. We assigned lineage to isolates from 2010, 2013-2016, and 2020 using genome-sequencing or allele-specific PCR. Seven and 30-day all-cause CFR were determined for the entire cohort. Univariate and multivariate analyses were conducted to determine if lineage affected risk of death.
Results
In total, 4,952 emm 1 iGAS cases were linked with demographic and mortality data; lineage was assigned to 1,356 cases. M1 UK was associated with a 30-day CFR of 24.4%, compared with 22.3% for M1 global , 10.5% for M1 23SNP , and 10.3% for M1 13SNP . After adjustment for age and sex, emm 1 lineage was not a significant risk factor for death within 7 or 30 days. Survival analysis highlighted rapid time to death as a feature of both M1 UK and M1 global. Most deaths (63.7%) occurred within 1d of diagnostic sampling. Of children under 15 who died, 56.3% died before any sampling, and 95.6% died within 1d of sampling.
Conclusions
Significant differences in mortality were not identified between M1 UK and M1 global but larger studies are required. Mortality due to emm 1 S. pyogenes is exceptionally high. Rapid time to death has implications for clinical trials: to impact death, interventions are required prior to culture-based diagnosis.
