SARS-CoV-2 and the Pandemic Surge in Invasive Group A Streptococcal Disease

BackgroundMultiple countries reported unprecedented increases in invasive group A streptococcal (iGAS) disease following widespread SARS-CoV-2 circulation. Whether this surge reflects reduced pathogen exposure during non-pharmaceutical interventions ("immunity debt") or effects of SARS-CoV-2 infection on host immunity remains unresolved. MethodsWe conducted a population-based time-series analysis of weekly iGAS incidence in central Ontario, Canada (population {approx}11 million) from March 2011 through March 2024 (676 weeks). Using negative binomial panel regression, we modeled acute (2-week lagged) and cumulative SARS-CoV-2 exposure while adjusting for seasonality, secular trends, age, and sex. Population attributable fractions (PAFs) were estimated by counterfactual prediction. Specificity was assessed through negative control analyses (influenza, RSV). The immunity debt hypothesis was evaluated using cumulative streptococcal exposure as a predictor of iGAS. ResultsAmong 2,906 iGAS episodes, 34.3% during the pandemic period were associated with acute SARS-CoV-2 effects (range by age group: 16.5-39.1%). Models incorporating cumulative SARS-CoV-2 burden showed markedly better fit ({Delta}AIC=-157.5); cumulative exposure was strongly associated with iGAS (IRR 1.193, 95% CI 1.151-1.235), increasing the estimated PAF to 66.7%. Cumulative effects were strongest in children (IRR 1.309). SARS-CoV-2 was comparably associated with non-invasive streptococcal disease, with no increase in invasion propensity. Cumulative streptococcal exposure was not protective (overall IRR 1.000, p=0.730); where significant, the association was positive, opposite to immunity debt predictions. ConclusionsCumulative SARS-CoV-2 burden was strongly associated with pandemic-era iGAS incidence. Cumulative streptococcal exposure did not support the immunity debt hypothesis. These ecological findings are consistent with SARS-CoV-2-associated immune dysregulation and warrant individual-level confirmation.