Phylodynamics of respiratory viruses : implications for public health

Abstract

Respiratory viruses, such as those responsible for the SARS epidemic, H1N1 swine flu pandemic, COVID-19 pandemic, and ongoing resurgence of highly pathogenic avian influenza (HPAI) H5 virus epidemics in poultry and wild birds, present significant public health concerns. Viral phylodynamics, integrating phylogenetic analysis with epidemiological, immunological, and ecological data, can enhance traditional epidemiological methods to better inform public health decision makers. Large-scale viral genome sequencing, especially since the COVID-19 pandemic, has provided unprecedented opportunities to comprehensively study viral molecular evolution during outbreaks. This thesis applies various phylodynamic frameworks to study the genomic epidemiology and molecular evolution of respiratory viruses, including SARS-CoV-2, human seasonal influenza, and avian influenza. The first chapter outlines the basics of the viruses under study alongside an introduction to viral phylodynamics. Chapter 2 investigates the genomic epidemiology of SARS-CoV-2 under an elimination strategy in Hong Kong, revealing that the majority of community cases stemmed from only two or three introductions in each of the five waves. Despite rapid implementation of local public health and social measures (PHSMs), the fifth wave in Hong Kong saw a resurgence in cases. Surveillance and sequencing strategies could be improved based on fluctuations in detection rates and discrepancies between different measures of virus spread. Chapter 3 examines the impact of non-pharmaceutical interventions for COVID-19 on global seasonal influenza activity, showing a decline in influenza viruses, with certain strains circulating in specific regions. The B/Yamagata lineage viruses appear to have been eliminated. Cryptic circulation of influenza viruses was observed in China during the 2020-2021 season, highlighting the importance of pathogen surveillance during relaxed pandemic measures. Chapter 4 addresses the unprecedented global outbreaks of HPAI H5N1 virus since 2020, leading to large-scale mortality in wild birds and incidental infections in mammalian hosts. There is a shift in the epicenter of HPAI H5 beyond Asia to new regions in Africa, the Middle East, Europe, and North and South America. The new H5N1 virus emerged from H5N8 through reassortment in wild birds. The spread globally and was characterized by extensive reassortment with low pathogenic avian influenza in domestic and wild birds. Earlier outbreaks of H5N8 were caused by a more stable genetic constellation, highlighting dynamic changes in HPAI H5 genomic evolution. The thesis also addresses the computational challenges inherent in phylodynamics, with Chapter 5 exploring the efficiency of novel deep learning methods as an alternative to traditional epidemiological methods. It underscores the potential of integrating contact tracing data to improve the accuracy of model predictions, particularly in scenarios involving superspreading events and low viral sequence variability. The concluding chapter summarizes key findings, discusses limitations, and outlines future research directions, emphasizing the value of this work in informing public health strategies and advancing our understanding of viral circulation and evolution.