  During its first two years, the SARS-CoV-2 pandemic manifested as multiple
waves shaped by complex interactions between variants of concern,
non-pharmaceutical interventions, and the immunological landscape of the
population. Understanding how the age-specific epidemiology of SARS-CoV-2 has
evolved throughout the pandemic is crucial for informing policy decisions. We
developed an inference-based modelling approach to reconstruct the burden of
true infections and hospital admissions in children, adolescents and adults
over the seven waves of four variants (wild-type, Alpha, Delta, Omicron BA.1)
during the first two years of the pandemic, using the Netherlands as the
motivating example. We find that reported cases are a considerable
underestimate and a generally poor predictor of true infection burden,
especially because case reporting differs by age. The contribution of children
and adolescents to total infection and hospitalization burden increased with
successive variants and was largest during the Omicron BA.1 period. Before the
Delta period, almost all infections were primary infections occurring in naive
individuals. During the Delta and Omicron BA.1 periods, primary infections were
common in children but relatively rare in adults who experienced either
re-infections or breakthrough infections. Our approach can be used to
understand age-specific epidemiology through successive waves in other
countries where random community surveys uncovering true SARS-CoV-2 dynamics
are absent but basic surveillance and statistics data are available.
