Background: The European Union has been criticized for responding to the COVID-19 pandemic in a reactive, rather than prosilient manner. For the EU bloc to be prosilient, it needs to have the right early warning indicators to allow short-term healthcare system preparedness and agile planning of the public health response. Method The association of COVID-19 disease burden, as measured by mortality (COVID-19 and all-cause), hospital and ICU occupancy, with incidence rate (IR), total positivity rate (TPR) and adjusted TPR as proposed by Vong and Kakkar, was investigated using Poisson regression analysis. This was carried out using both real-time data and time lags of up to 8 weeks to identify potential for early warning of spikes in disease burden. ECDC weekly figures for these indicators were used, and the analysis was repeated for the subset of data after Week 42  of 2020, when the EU Council introduced minimum COVID-19 testing rates. Results TPR and IR were noted to be the most predictive of COVID-19 disease burden whilst adjusted TPR applied on weekly data was not associated. TPR behaved better at predicting all-cause mortality in both analyses. The TPR and IR were both best associated with hospital and ICU occupancy and COVID-19 mortality with a short time lag (2–3 weeks in the case of TPR with hospital occupancy and COVID-19 mortality). Conclusions Monitoring TPR can provide a 2–3-week warning of a spike in hospital occupancy and COVID-19 mortality. This time, if well utilized, could help health systems save countless lives by mobilising resources.