{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/60412"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/60412","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"SARS-COV-2 EVOLUTION AND TRANSMISSION: WITHIN-HOST, BETWEEN-HOST, AND BETWEEN-SPECIES","abstract":"The evolution and adaptation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, remain incompletely understood. This thesis aims to elucidate the temporal and mechanistic aspects of these viral changes through comprehensive genomic analyses. Specifically, we investigate the evolution of SARS-CoV-2 within immunocompromised individuals with prolonged infections, compare viral adaptations between vaccinated and unvaccinated hosts, and explore interspecies transmission between humans and animals. We found that SARS-CoV-2 evolution rates are increased during prolonged immunocompromised infection, with dominant drug resistant substitutions arising within weeks of treatment. In a population-based analysis, we found evidence of evolution selecting for immune evasive substitutions and preferential transmission of more recent lineages among vaccinated individuals. In a study to examine an animal spillover to we identified the first published Delta variant infection in domestic cats. In a study to examine spillover in wild animals, we identified multiple spillovers and chains of transmission among white-tailed deer in 2021. Later we performed a 1,017 day longitudinal study in Pennsylvania white-tailed deer where we identified seasonal trends of SARS-CoV-2 infection rates, preferential infection for deer in primarily crops/pasture land compared to forest, and persistence of divergent ancestral viral variants in the deer viral reservoir. Together these findings suggest the rise of SARS-CoV-2 variants with increased fitness in humans might most rapidly appear in immunocompromised prolonged infections, but there remains a danger of spill back from highly divergent lineages from animal reservoirs.","abstract_html":"The evolution and adaptation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, remain incompletely understood. This thesis aims to elucidate the temporal and mechanistic aspects of these viral changes through comprehensive genomic analyses. Specifically, we investigate the evolution of SARS-CoV-2 within immunocompromised individuals with prolonged infections, compare viral adaptations between vaccinated and unvaccinated hosts, and explore interspecies transmission between humans and animals. We found that SARS-CoV-2 evolution rates are increased during prolonged immunocompromised infection, with dominant drug resistant substitutions arising within weeks of treatment. In a population-based analysis, we found evidence of evolution selecting for immune evasive substitutions and preferential transmission of more recent lineages among vaccinated individuals. In a study to examine an animal spillover to we identified the first published Delta variant infection in domestic cats. In a study to examine spillover in wild animals, we identified multiple spillovers and chains of transmission among white-tailed deer in 2021. Later we performed a 1,017 day longitudinal study in Pennsylvania white-tailed deer where we identified seasonal trends of SARS-CoV-2 infection rates, preferential infection for deer in primarily crops/pasture land compared to forest, and persistence of divergent ancestral viral variants in the deer viral reservoir. Together these findings suggest the rise of SARS-CoV-2 variants with increased fitness in humans might most rapidly appear in immunocompromised prolonged infections, but there remains a danger of spill back from highly divergent lineages from animal reservoirs.","abstract_has_math":false,"creators":["Marques, Andrew, David"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bushman, Frederic, D"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-24T03:45:38Z","subjects":["Life Sciences"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/60412","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bushman, Frederic, D"]},{"key":"dc:creator","label":"Author","values":["Marques, Andrew, David"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-08-28T16:08:00Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-08-28T16:08:00Z"]},{"key":"dc:date.issued","label":"Date","values":["2024"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation/Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Life Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://repository.upenn.edu/handle/20.500.14332/60412"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The evolution and adaptation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, remain incompletely understood. This thesis aims to elucidate the temporal and mechanistic aspects of these viral changes through comprehensive genomic analyses. Specifically, we investigate the evolution of SARS-CoV-2 within immunocompromised individuals with prolonged infections, compare viral adaptations between vaccinated and unvaccinated hosts, and explore interspecies transmission between humans and animals. We found that SARS-CoV-2 evolution rates are increased during prolonged immunocompromised infection, with dominant drug resistant substitutions arising within weeks of treatment. In a population-based analysis, we found evidence of evolution selecting for immune evasive substitutions and preferential transmission of more recent lineages among vaccinated individuals. In a study to examine an animal spillover to we identified the first published Delta variant infection in domestic cats. In a study to examine spillover in wild animals, we identified multiple spillovers and chains of transmission among white-tailed deer in 2021. Later we performed a 1,017 day longitudinal study in Pennsylvania white-tailed deer where we identified seasonal trends of SARS-CoV-2 infection rates, preferential infection for deer in primarily crops/pasture land compared to forest, and persistence of divergent ancestral viral variants in the deer viral reservoir. Together these findings suggest the rise of SARS-CoV-2 variants with increased fitness in humans might most rapidly appear in immunocompromised prolonged infections, but there remains a danger of spill back from highly divergent lineages from animal reservoirs."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:title","label":"Title","values":["SARS-COV-2 EVOLUTION AND TRANSMISSION: WITHIN-HOST, BETWEEN-HOST, AND BETWEEN-SPECIES"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bushman, Frederic, D"],"dc:creator":["Marques, Andrew, David"],"dc:date.accessioned":["2024-08-28T16:08:00Z"],"dc:date.available":["2024-08-28T16:08:00Z"],"dc:date.issued":["2024"],"dc:description.abstract":["The evolution and adaptation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, remain incompletely understood. This thesis aims to elucidate the temporal and mechanistic aspects of these viral changes through comprehensive genomic analyses. Specifically, we investigate the evolution of SARS-CoV-2 within immunocompromised individuals with prolonged infections, compare viral adaptations between vaccinated and unvaccinated hosts, and explore interspecies transmission between humans and animals. We found that SARS-CoV-2 evolution rates are increased during prolonged immunocompromised infection, with dominant drug resistant substitutions arising within weeks of treatment. In a population-based analysis, we found evidence of evolution selecting for immune evasive substitutions and preferential transmission of more recent lineages among vaccinated individuals. In a study to examine an animal spillover to we identified the first published Delta variant infection in domestic cats. In a study to examine spillover in wild animals, we identified multiple spillovers and chains of transmission among white-tailed deer in 2021. Later we performed a 1,017 day longitudinal study in Pennsylvania white-tailed deer where we identified seasonal trends of SARS-CoV-2 infection rates, preferential infection for deer in primarily crops/pasture land compared to forest, and persistence of divergent ancestral viral variants in the deer viral reservoir. Together these findings suggest the rise of SARS-CoV-2 variants with increased fitness in humans might most rapidly appear in immunocompromised prolonged infections, but there remains a danger of spill back from highly divergent lineages from animal reservoirs."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/60412"],"dc:language.iso":["en"],"dc:subject":["Life Sciences"],"dc:title":["SARS-COV-2 EVOLUTION AND TRANSMISSION: WITHIN-HOST, BETWEEN-HOST, AND BETWEEN-SPECIES"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:45:38Z"}