Risk Factors for Severe Pediatric Invasive Group A Streptococcal Disease.

Importance: An increase in pediatric cases of invasive group A streptococcus (iGAS) disease was noted in the Netherlands starting in early 2022. GAS disease can range from mild to life-threatening invasive infections. Clinical and public health decisions rely on timely and detailed reporting of clinical data. Objective: To determine risk factors associated with severe pediatric iGAS, defined as requiring admission to an intensive care unit and/or death, and to analyze pediatric iGAS incidence, presentations, and outcome between pre-COVID-19 pandemic (January 2015 to March 2020), COVID-19 pandemic (April 2020 to December 2021), and post-COVID-19 pandemic (January 2022 to June 2024) periods. Design, Setting, and Participants: This observational, retrospective and prospective cohort study in 20 hospitals (tertiary and nontertiary) in the Netherlands was conducted from January 2015 to June 2024, with real-time reporting of data on the study website since January 2022. Children aged 0 to 17 years with iGAS (positive culture or polymerase chain reaction test and/or clinical presentation) were included. Exposure: iGAS infection. Main Outcome and Measures: The primary outcome was risk factors for severe iGAS; secondary outcomes included iGAS incidence rate and clinical phenotypes prior, during, and after the COVID-19 pandemic. Risk factors for severity and mortality were analyzed using univariable and multivariable logistic regression analyses, and incidence rate ratios (IRRs) between pre-COVID-19 and postCOVID-19 pandemic periods were calculated using Poisson regression. Results: Of 617 children included, 351 (56.9%) were aged 0 to 4 years. For the 192 participants with detailed data collection, median (IQR) age was 4.2 (1.7-7.1) years and 91 (47.4%) were male. iGAS cases decreased during the COVID-19 pandemic and increased significantly in the post-COVID-19 period (IRR, 2.93; 95%, 2.46-3.49), as compared with the pre-COVID-19 pandemic period. By late 2023, the incidence of iGAS returned to pre-COVID-19 pandemic levels. Factors associated with increased risk of severe disease included a post-COVID-19 pandemic diagnosis (odds ratio [OR], 3.49; 95% CI, 2.31-6.26), pulmonary involvement (OR, 8.64; 95% CI, 5.50-13.55), streptococcal toxic shock syndrome (STSS; OR, 11.71; 95% CI, 4.39-31.18), and meningitis or encephalitis (OR, 4.38; 95% CI, 4.39-31.18). Clinical factors associated with increased risk of severe disease were reduced consciousness (OR, 7.61; 95% CI, 1.84-34.41), dyspnea (OR, 9.89; 95% CI, 3.04-32.14), abnormal auscultation (OR, 6.32; 95% CI, 2.18-18.32), and elevated C-reactive protein (OR, 6.32; 95% CI, 2.18-18.32), while estimated glomerular filtration rate was associated with a decreased risk (OR, 0.64; 95% CI, 0.49-0.84). Disease severity increased in post-COVID-19-pandemic cases, with higher mortality (13 of 294 cases [4.4%] vs 3 of 218 cases [1.4%]) and intensive care admission rates (113 of 294 cases [38.4%] vs 34 of 218 cases [15.6%]), as compared with pre-COVID-19 pandemic cases. Severity of pulmonary iGAS was similar in both periods. In the post-COVID-19 pandemic period, there was a significant increase in the incidence of pulmonary infections (IRR, 5.04; 95% CI, 3.27-7.97) , STSS (IRR, 10.30; 95% CI, 3.88-35.60), meningitis or encephalitis (IRR, 12.30; 95% CI, 4.14-52.70), and necrotizing fasciitis (IRR, 26.10; 95% CI, 5.14-475.00). Conclusions and Relevance: In this cohort study, risk factors for a complicated course of iGAS in children included pulmonary or central nervous system involvement, STSS, reduced consciousness or pulmonary clinical signs, elevated CRP, and decreased eGFR. Awareness of these risk factors is important to improve timely recognition of at-risk cases and improve clinical outcomes.