UC San Diego

Pandemics pose a persistent and substantial threat to human health, with consequences that include widespread mortality and suffering, with the 21st century thus far most dramatically affected by the coronavirus disease 2019 (COVID-19) pandemic. Understanding the origins of a pandemic is critical in preventing future epidemics and pandemics. This dissertation investigates the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. First, I present a novel approach coupling phylogenetics and epidemic modeling to infer when the primary case of the COVID-19 pandemic was infected. I then expand on this approach, incorporating additional epidemiological data and interrogating likely phylogenetic structures, to determine that the COVID-19 pandemic is likely the result of at least two separate cross-species transmission events of SARS-CoV-2 into humans. Finally, I examine sarbecoviruses closely related to SARS-CoV and SARS-CoV-2 to reconstruct the temporal and geographic history of these viruses. Taken together, this dissertation outlines the events both preceding and at the start of the COVID-19 pandemic, identifying SARS-CoV-2 as a zoonotic pathogen, and implicating the wild and farmed animal trade in the emergence of SARS-CoV and SARS-CoV-2.