General introduction 19 1 Subsequent phases of the pandemic, locally and globally Following the first surge of COVID-19 cases worldwide, numerous subsequent waves of the pandemic occurred globally. Each regional wave was characterised by specific features, owing to the constant evolution of the virus and fluctuating population immunity over time. As such, the risk-benefit balance of restrictions had to be constantly re-evaluated, recognising the impact of long-term lockdowns on mental health[51], education[52], and the economy[53]. The rise of numerous new variants of concern (VoC), each of which demonstrated changes in either transmissibility, virulence, or escape from existing immunity, required repeated epidemiological assessments. The Delta variant (Pango lineage B.1.617.2), for instance, is likely to have arisen in India[54] and was first imported in the Netherlands by young adults who had celebrated finishing high school by travelling together to Portugal and Spain. This variant caused international concern due to its increased virulence[54]. Fortunately, vaccination was repeatedly demonstrated to be effective in protecting against hospitalisation with a Delta variant infection[55]. In contrast, in December 2021, the Omicron variant (B.1.1.529) was found to have developed numerous mutations related to antibody escape[56], but less frequently led to severe disease and hospitalisation compared to the Delta variant – although elderly individuals remained at highest risk[57]. At the time of writing, a combination of viral evolution towards less virulent variants (Omicron sub-variants; Pango lineages BA.1 to XBB1.9), high levels of humoral and cellmediated immunity in the Dutch population (through natural, vaccine-derived and hybrid immunisation), and advances in the clinical management of COVID-19 patients, means that COVID-specific restrictions have been lifted in the Netherlands since March 2022[59] and replaced by general measures for the prevention of respiratory pathogens.
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