Paediatric invasive group A streptococcal infections and associations with viral infections in 15 European countries after lifting non-pharmaceutical interventions against SARS-CoV-2: an interrupted time-series analysis

Background: After lifting non-pharmaceutical interventions (NPIs) against the transmission of SARS-CoV-2, various countries experienced an increase in invasive Group A Streptococcal (iGAS) infections. We aimed to characterise the paediatric outbreak across Europe and to analyse the influence of viral infections. Methods: We conducted an interrupted time-series analysis based on data from 15 European countries from the PEGASUS consortium. We assessed the evolution of the number of iGAS cases aged 1 month to 18 years between 01/01/2018 and 03/31/2024, comparing the post-NPIs period (01-04-2022 until 31-03-2024) to the baseline period (01-01-2018 until 31-03-2020). Further analyses were performed by country, clinical phenotype, age and severity, including sensitivity analyses. We then explored whether certain iGAS phenotypes correlated with trends in RSV, influenza and VZV across countries over time using Google Trends data. Findings: We included 2091 iGAS cases over the study period; 79 children (3.6%) died and 580 (27.7%) required PICU admission. We estimated an overall increase of +229.8% (95% CI (141.9–341.6)) among iGAS cases from October 2022 to March 2024, compared to the baseline period. The observed increases varied across clinical phenotypes, ranging from +62.7% (95% CI (8.3–157.9)) for osteo-articular infections to +238.7% (95% CI 75.8–464.8) for pneumonia. We observed a strong correlation between the incidence of iGAS pneumonia and RSV (Rho: 0.57, 95% CI [0.11–0.79]) and influenza (Rho 0.69, 95% CI 0.35–0.87); and between skin and soft tissue infections and VZV (Rho: 0.73, 95% CI [0.42–0.89]). Interpretation: The patterns observed across Europe during this outbreak demonstrate an association between respiratory viruses as well as VZV, and iGAS. Funding: This study has received funding from ESPID, INOPSU and the Northwest Clinics. The COPP study group was supported by grants of the Dutch National Health Council (ZonMW) project number 10430072110007 and the Christine Bader Foundation.