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Principal Investigator: Amy K Barczak
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $846,387
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Immunosuppressed individuals are increasingly recognized as a focal point of the COVID-19 epidemic. They are
at increased risk of chronic COVID-19 infection, therapeutic treatment failure, severe disease and COVID-19
mortality. Evidence is also emerging that they may also be drivers of COVID-19 variant/subvariant emergence,
due to their risk of prolonged infection and accelerated viral evolution. However, the immune and viral
mechanisms by which chronic infection, viral evolution, and drug resistance occur in this population are poorly
understood. To improve health outcomes for this high-risk population and to reduce the risk of viral evolution and
drug resistance, there is an urgent need to address gaps in our understanding of which immune deficiencies
increase the risk of chronic COVID-19 infection and accelerated viral evolution. The primary goal of this proposal
is to determine the host and virologic characteristics that promote chronic viral infection and viral evolution. The
proposing investigators will an existing translational research infrastructure with experience recruiting cohorts
of immunosuppressed individuals with COVID-19 and broad expertise in clinical research, viral quantification,
viral culture, sequencing, and immunology. The results will provide critical new data about COVID-19
pathogenesis, variant evolution, therapeutic response, and inform the clinical care of immunosuppressed
populations. By deepening our understanding of the immune pathways of viral clearance, the results from this
proposal may also identify potential targets for the next generation of vaccines and therapeutics.
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induced mortality><COVID-19 infection><COVID-19 mortality><COVID-19 pandemic><COVID-19 pathogenesis><COVID-19 period><COVID-19 public health crisis><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 therapeutics><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 virus infection><COVID-19 years><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 death><COVID19 fatality><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 pathogenesis><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 virus><CV-19><Characteristics><Chronic><Clinical Research><Clinical Study><Clinical Treatment Moab><CoV-2><CoV2><Collaborations><Coronavirus Infectious Disease 2019><Data><Disease><Disorder><Drug resistance><Enrollment><Epidemiology><Evolution><General Population><General Public><Genes><Genetic><Goals><HSC transplantation><Health><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematopoietic Cancer><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Immune><Immune response><Immunes><Immunochemical Immunologic><Immunocompetent><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Immunosuppressed Host><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Incidence><Individual><Infection><Investigators><Laboratories><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Malignant Hematologic Neoplasm><Methods><Monoclonal Antibodies><Nature><Non-Polyadenylated RNA><Outcome><Participant><Pathway 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epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 therapeutics><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Source><Symptoms><T cell response><T8 Cells><T8 Lymphocytes><Therapeutic><Translational Research><Translational Science><Transmission><Treatment Failure><Variant><Variation><Viral><Viral Burden><Viral Diseases><Viral Drug Resistance><Viral Load><Viral Load result><Virus><Virus Diseases><Wuhan coronavirus><aminoacid><anti-viral compound><anti-viral development><anti-viral drug development><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-viral therapeutic development><anti-viral therapy development><anti-virals><antibody titering><antiviral development><antiviral drug 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