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ObjectivesPaediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases.MethodsSARS-CoV-2 infections in CYP aged 0–15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections.ResultsDuring the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037–0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025–0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model.ConclusionsThe model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant.