Novel emm 4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022.

Invasive group A streptococcal (iGAS) disease cases increased in the first half of 2022 in the Netherlands, with a remarkably high proportion of emm 4 isolates. Whole-genome sequence analysis of 66 emm 4 isolates, 40 isolates from the pre-coronavirus disease 2019 (COVID-19) pandemic period 2009-2019 and 26 contemporary isolates from 2022, identified a novel Streptococcus pyogenes lineage (M4 _NL22 ), which accounted for 85 % of emm 4 iGAS cases in 2022. Surprisingly, we detected few isolates of the emm 4 hypervirulent clone, which has replaced nearly all other emm 4 in the USA and the UK. M4 _NL22 displayed genetic differences compared to other emm 4 strains, although these were of unclear biological significance. In publicly available data, we identified a single Norwegian isolate belonging to M4 _NL22 , which was sampled after the isolates from this study, possibly suggesting export of M4 _NL22 to Norway. In conclusion, our study identified a novel S. pyogenes emm 4 lineage underlying an increase of iGAS disease in early 2022 in the Netherlands and the results have been promptly communicated to public health officials.