"Outbreak Dynamics of Emerging SARS-CoV-2 Variants in Human and Animal " by Rebecca Lynn Earnest

Date of Award

Fall 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Public Health

First Advisor

Grubaugh, Nathan

Abstract

The COVID-19 pandemic is characterized by cycles of SARS-CoV-2 viral variant emergence followed by surges of infections and deaths. In the United States, the most notable variants to date are Alpha (B.1.1.7), Delta (B.1.617.2 and AY.x sub-lineages), and Omicron (BA.1, BA.2, BA.4, BA.5, and various sub-lineages). Pandemic response evolved along with the virus, raising three overarching research questions with each new variant that correspond to the chapters of this dissertation. When a new variant emerges, how is it different from the previously dominant variant(s) in circulation? The set of mutations that define a SARS-CoV-2 variant can affect viral properties such as transmissibility, disease severity, immune escape, and the effectiveness of existing diagnostics, treatments, and vaccines. The extent to which these properties differ between variants depends not only on innate features of the viral variant, but also on features of the population in which the variant circulates. In Chapter 1, we focused on one variant property, transmissibility, and formed a large collaboration to estimate the relative transmissibility of the emerging Delta variant relative to Alpha across six New England states. We explored the degree to which relative transmissibility estimates varied by state and differed from published estimates from other countries, clarifying the extent to which such estimates are location-specific. In addition, we explored one possible innate source of increased relative transmissibility: higher viral loads. How should we adapt public health policies to the new variant? Due to the evolving epidemic dynamics driven by SARS-CoV-2 variants, public health policies need to be periodically updated. Such policy changes are not made in a vacuum, but rather necessitate an understanding of the resources, behaviors, and needs of the target population. In Chapter 2, we conducted a study to inform university COVID-19 isolation policy in response to the emerging Omicron (BA.1) variant, which drove an unprecedented surge of infections in the United States. During this period, the Centers for Disease Control and Prevention halved the isolation period from 10 to five days without an exit test based on limited data from earlier variants. Concerned about the prospect of outbreaks in high-density university dormitory housing, we conducted a study in which university students underwent daily rapid antigen testing and assessed the duration of and factors associated with test positivity duration. The findings enabled a university policy that tailored isolation periods based on exit testing, with applications to other high-density settings. What may be sources of future outbreaks, including those caused by unexpected variants? Omicron (BA.1) possessed an extensive set of unexpected mutations and one analysis found that its closest genetic ancestor pre-dated its detection by more than a year. Since its emergence, Omicron and its descendants have dominated the variant landscape. One hypothesis for the origin of similarly unexpected variants is adaptive evolution within novel non-human hosts. In addition, even in the absence of unexpected viral evolution, new animal reservoirs could serve as increasingly important sources of future outbreaks as community transmission diminishes. In Chapter 3, we explore the potential long-term risk to human health posed by SARS-CoV-2 spillback into rodents in Connecticut. We sampled white-footed mice (Peromyscus leucopus) to assess both SARS-CoV-2 past exposure and active infection. In addition, we also sampled white-tailed deer (Odocoileus virginianus), a known SARS-CoV-2 susceptible species, from similar habitats to provide a comparison. The research elucidates the extent to which white-footed mice may pose a long-term health risk and contributes to our currently limited understanding of SARS-CoV-2 spillback into and circulation within animal populations. In this dissertation, we address research questions relevant to the continually evolving SARS-CoV-2 variant landscape. Specifically, we estimate variant relative transmissibility in Chapter 1, examine how university COVID-19 policy should change in response to a new variant in Chapter 2, and explore SARS-CoV-2 at the animal-human interface to understand possible sources of future outbreaks in Chapter 3. Together, the chapters integrate data from multiple sources (epidemiological, viral genomic, serological, and diagnostic) to inform COVID-19 response to emerging variants and can serve as case studies for future outbreaks.

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