Invasive group A streptococcal infections in children and adolescents in Denmark during 2022-23 compared with 2016-17 to 2021-22: a nationwide, multicentre, populationbased cohort study

Background A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22). Methods In this nationwide, multicentre, population -based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's chi 2 test. Findings Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 226 (95% CI 147-331) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 660 (520-826) per 1 000 000 during 2023-23 (RR 29, 95% CI 19-46; p<00001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 61 (95% CI 24-125) per 1 000 000 children and adolescents. In 2022-23, there was a 95-fold increase in emm-12 (95% CI 22-408; p=00002) and a 27-fold increase in emm-1 (13-55; p=00037). The most common clinical manifestations of iGAS in 2022-23 were softtissue infections, which increased by 45-fold (19-109; p=00003), and complicated pneumonia with parapneumonic effusion, which increased by 40-fold (14-114; p=00059), both compared with the three preCOVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=039), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=053), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=084), or mortality (three [4%] of 76 vs three [3%] of 98; p=100). In 2022-23, there was a 36-fold (95% CI 18-73; p=00001) increase in children with a preceding upper respiratory tract infection and a 46-fold (15-141; p=00034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons. Interpretation In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three preCOVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents.