Genomic methods for the surveillance and epidemiologic inference of respiratory viral pathogens

Abstract

Respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV), are globally circulating pathogens with a substantial disease burden. Epidemiologic and genomic approaches to surveil respiratory viruses guide public health efforts and advance our understanding of viral evolution and transmission. However, interpreting respiratory viral surveillance data can be challenging, as data collection is often (i) biased, in that epidemiologic and genomic data are primarily derived from cases exhibiting moderate or severe disease; and (ii) dynamic, in that surveillance practices evolve in response to diagnostic practices, methodologic advances, and public health priorities. In this dissertation, I develop methods to mitigate the biases inherent in traditional respiratory viral surveillance approaches, and apply them to study the epidemiology and evolution of both SARS-CoV-2 and RSV. In Chapter 2, I use scalable genomic tools and samples from universal SARS-CoV-2 testing programs to conduct population-wide genomic surveillance, providing a comprehensive view of the Omicron variant’s arrival and spread in university communities. In Chapter 3, I develop an experimental protocol to sequence viral genomes from at-home rapid antigen tests, allowing genomic surveillance to extend to individuals who do not seek clinical diagnostic testing. In Chapters 4 and 5, I investigate the increase in RSV cases reported after the emergence of SARS-CoV-2. I demonstrate that increased respiratory viral testing, rather than the evolution of a more severe or transmissible RSV variant, can explain the apparent increase in cases. Moreover, I establish quantitative approaches to estimate epidemic parameters under the counterfactual scenario in which viral diagnostic testing remained unchanged. In summary, I develop robust genomic and epidemiologic surveillance strategies and demonstrate their ability to generate actionable insights into the evolution and transmission of respiratory viruses.