Influenza Dynamics from Pre-pandemic to Post-pandemic Periods: Epidemiology and Genetic Characteristics
Influenza remains a major global public health concern, causing annual epidemics and potentially instigating pandemics. Despite available seasonal vaccines, influenza still causes significant mortality and morbidity in Australia, particularly among vulnerable populations. The COVID-19 pandemic and subsequent public health measures significantly impacted the circulation of many respiratory viruses, including influenza viruses. While previous studies have examined broader trends of various respiratory viruses throughout the COVID-19 pandemic, research on influenza epidemiology and evolution in Australia spanning the pre- to post-pandemic periods remains limited. This PhD research aims to conduct comprehensive epidemiological and genomic analyses to elucidate changes in influenza epidemiology and viral evolution during this critical period, providing important insights for public health responses. Analysis of local diagnostic PCR data from two major metropolitan health districts found a near-absence of influenza viruses between April 2020 and 2021, followed by a resurgence of cases in 2022 (Chapter 2). Notably, peak influenza activity in 2022 and 2023 occurred earlier compared to most pre-pandemic years, underscoring the importance of continued surveillance to determine whether this represents a temporary phenomenon or a sustained alteration in influenza activity. Utilizing a developed high-throughput whole genome sequencing (WGS) protocol, complete genomes of influenza A and B viruses (IAVs and IBVs) circulating during the 2019 season were obtained (Chapter 3). Analysis of these genomes revealed the genetic diversity and evolution of influenza viruses during the period prior to the COVID-19 pandemic and identified potential amino acid substitutions associated with genotypic antiviral drug susceptibility and increased virulence. This provided reference information for genomic analysis of influenza viruses during the resurgence of cases in 2022 (Chapter 4). Chapter 4 investigated the resurgence of influenza in 2022, focusing on whole genome sequencing of A/H3N2 viruses (predominant subtype circulating in this season). Phylogenetic analysis demonstrated the evolution of A/H3N2 viruses, and a reduction in their genetic subclade diversity compared to the pre-pandemic season. Whole-genome analysis also identified a high frequency of interclade reassortment events between subclades 3C.2a1b.2a.2 and 3C.2a1b.1a, previously unreported in Australia. Furthermore, Bayesian phylogeographic analysis elucidated the spatiotemporal spread of A/H3N2 viruses within Australia during this season. These findings provide critical insights into phylodynamics of A/H3N2 viruses in the post-pandemic era in Australia. In summary, this research enhanced our understanding of influenza epidemiology and evolution in Australia across the pre- to post-pandemic periods, particularly for the phylodynamics of A/H3N2 viruses following their two-year near-absence. The implementation of a high-throughput WGS protocol facilitated comprehensive genomic analyses, enabling the identification of potential mutations associated with antiviral drug resistance and virulence, as well as the detection of interclade reassortment viruses. These findings provide valuable reference information for future public health interventions and underscore the importance of continued surveillance in the post-pandemic era.
Influenza, High-throughput sequencing, Phylogeography, anzsrc-for: 320705 Medical virology
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