Abstract The trajectory of COVID-19 epidemic waves in the general population of Belgium was analysed by defining quantitative criteria for epidemic waves from March 2020 to early 2023. Peaks and starting/ending times characterised nine waves numerated I to IX based on the daily reported incidence number (symbol INCID) and three “endemic” interval periods between the first four waves. The SIR compartmental model was applied to the first epidemic wave by fitting the daily prevalence pool (symbol I) calculated as the sum of the daily incidence rate and estimated number of subjects still infectious from the previous days. The basic reproductive number R0 was calculated based on the exponential growth rate during the early phase and on medical literature knowledge of the time of generation of SARS-CoV-2 infection. The first COVID-19 wave was well fitted by an open SIR model. According to this approach, dampened recurrent epidemic waves evolving through an endemic state would have been expected. This was not the case with the subsequent epidemic waves being characterised by new variants of concern (VOC). Evidence-based observations: 1) each epidemic wave affected less than a fifth of the general population; 2) the Vth epidemic wave (VOC Omicron) presented the greatest amplitude. The lack of recurrence of the same VOC during successive epidemic waves strongly suggests that a VOC has a limited persistence, disappearing from the population well before the expected proportion of the theoretical susceptible cohort being maximally infected. Fitting the theoretical SIR model, a limited persistence of VOCs in a population could explain that new VOCs replace old ones, even if the new VOC has a lower transmission rate than the preceding one. In conclusion, acquisition of potential defective mutations in VOC during an epidemic wave is a potential factor explaining the absence of resurgence of a same VOC during successive waves. Such an hypothesis is open to discussion and to rebuttal. A modified SIR model with epidemic waves of ...