COVID-19: Identifying Molecular Signatures in adults and children with COVID-19 by Proteomics
EMSL Project ID
60079
Abstract
A novel coronavirus, SARS-CoV-2, recently emerged rapidly transmitting from person-to-person causing widespread disease (COVID-19). Many adults progress to severe OVID-19 and African American have higher risk of hospitalization and mortality. In contrast, children generally present with more mild symptoms and disease progression. There are very few experimental studies of diverse cohorts of adults and children. This study aims to define clinical, immunologic, and virologic characteristics of COVID-19 in a diverse population of adults and children to identify clinical, biological, and viral variables as well as cellular and molecular signatures that associate with progression to severe disease. Our first objective is to define clinical characteristics and subject variables that influence the progression of COVID-19 in a diverse cohort of adults and children. This will include monitoring viral and normal flora dynamics in nasal fluids repeatedly over one month and from stool samples collected at enrollment and one month later. Our second objective is to characterize and quantify the host response of adults and children at the site of SARS-CoV-2 infection. We hypothesize that children have a uniquely active and aggressive innate immune response in their upper airways that makes them rather resistant to COVID-19 while adults have slower diminished responses at the site of infection promoting replication and invasion. Then, in adults, when the immune system is finally activated it senses this deep and thorough invasion and overreacts. We will collect nasal fluids and cells from adults and children with a range of disease severity and healthy controls, and compare their responses by quantifying gene and protein expression in immune and epithelial cells as well as soluble factors that influence host pathogen interactions. We will evaluate the expression of genes in infected and uninfected epithelial cells within COVID-19 positive and influenza infected subjects to determine the molecular basis of how SARS-CoV-2 initiates more pathogenesis at the single cell level and distinguish infected from bystander responses. The final objective in this proposal is to determine systemic immune response dynamics in adults and children with COVID-19 overtime, including high resolution analysis of T cells that mediate viral clearance and immune memory. We posit that, in addition to their robust initial response detailed above, recent encounters with seasonal coronaviruses that are new to children improve the quality and quantity of their adaptive response to SARS-CoV-2. We will define the immune response in blood of mild, moderate, and severe cases of COVID-19 in terms of immune cell populations and their activation status and the effector proteins they secrete. We will also compare the specificity of T cell responses and T cell receptors from blood samples from healthy children or infected with seasonal coronavirus before 2019 and those with moderate COVID-19. Finally, we will apply statistical models and machine learning algorithms to identify biomarkers that predict progression to severe disease based on quantitative and qualitative variables. Comprehensive proteomics is critical to both the local and systemic studies and
Project Details
Project type
Limited Scope
Start Date
2021-09-30
End Date
2022-09-30
Status
Closed
Released Data Link
Team
Principal Investigator