Characterizing Within-Host Evolution in Prolonged SARS-CoV-2 Infections: A Comprehensive Study Utilizing the Moran Model and Fitness Landscape Analysis Restricted; Files Only

Abstract

Prolonged infections in immunocompromised individuals are increasingly recognized as potential sources for the emergence of viral variants, as evidenced by the SARS-CoV-2 VOCs, Alpha and Omicron. The plausibility of prolonged infections seeding new viral variants at the population level is supported by a large number of studies that have documented extensive patterns of genetic and phenotypic evolution in prolonged infections. Plausibility is also supported by genetic and phylogenetic patterns that have characterized new VOCs. Within-host evolutionary analysis of SARS-CoV-2 chronic infections has shown that there is tremendous heterogeneity in evolutionary patterns across individuals, where some chronic SARS-CoV-2 infections can have multiple lineages evolve and co-circulate while others don’t. In our study, utilizing a theoretical framework that incorporates a tunably rugged fitness landscape, we employed the Moran Model under a Strong Selection Strong Mutation (SSSM) regime to simulate the evolutionary dynamics of SARS-CoV-2 in a host environment over time. Findings from our simulations reveal that the evolutionary paths taken by the virus within hosts are influenced by multiple factors, including the size of the effective viral population and the ruggedness of the fitness landscape, which in turn affects the antigenic evolution of the virus. Importantly, we observe that pleiotropic mutations play a significant role in shaping viral adaptation, with the potential to both facilitate and impede the evolution of antigenic characteristics depending on the immune escape they afford the virus. The study underscores the complexity of viral evolution in prolonged infections and highlights the need for a deeper understanding of how within-host dynamics contribute to the emergence of new variants at the population level. Ultimately, this work enhances our understanding of the mechanisms driving the evolution of VOCs and provides insights into the potential for chronic infections to act as reservoirs for future outbreaks. 

Table of Contents

Abstract ..........................................................................................2

Introduction....................................................................................3

Method ...........................................................................................6

Result ... .........................................................................................17

Discussion......................................................................................24

References .....................................................................................28 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Ecology Biology, Evolution and Development
Stichwort	Evolution Epidemiology SARS-CoV-2 Disease Ecology
Committee Chair / Thesis Advisor	Katia Koelle, Emory University
Committee Members	Rustom Antia, Emory University Michal Arbilly, Emory University

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