Abstract
Despite intensive study, gaps remain in our understanding of SARS-CoV-2 transmission patterns during the COVID-19 pandemic, in part due to limited contextual metadata accompanying most large genomic surveillance datasets. We analyzed over 130,000 SARS-CoV-2 genomes, over 85,000 with matched epidemiological data, collected in Massachusetts from November 2021 to January 2023, to investigate viral transmission dynamics at high resolution. The data were drawn from diagnostic testing at >600 facilities representing schools, workplaces, public testing, and other sectors, and encompass the emergence of six major viral lineages, each representing a new outbreak. We found urban areas as key hubs for new lineage introduction and interurban transmission as facilitating spread throughout the state. Young adults, especially those on college campuses, served as early indicators of emerging lineage dominance. Resident-aged populations in college campuses and nursing homes exhibited a higher likelihood of being linked to within-facility transmission, while staff-aged at those facilities were more linked to their surrounding community. Individuals with recent vaccine doses, including boosters, had a lower likelihood of initiating transmission. This dataset shows the value of linking genomic and epidemiologic data at scale for higher resolution insights into viral dynamics and their implication for public health strategy.