Proteomics Core: Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity

Project Summary/Abstract In Dec 2019, a cluster of respiratory illness in Wuhan China defined the onset of a worldwide pandemic involving novel coronavirus (SARS-CoV-2). SARS-CoV-2 infected patients are frequently asymptomatic, but initial epidemiologic estimates from the WHO indicate that ~15% of patients develop severe disease including viral pneumonia often requiring ICU care due to progression to develop life-threatening complications including (but not limited to) shock and secondary organ failures, and super-infections. Risk factors for increased mortality from COVID-19 include older age, COPD, ischemic heart disease, diabetes mellitus, and immunosuppression. Although direly needed, no targeted therapies or vaccinations are available as of now. Major research efforts have been launched towards the development of anti-SARS-CoV-2 vaccines, including those within Boston Children's Hospital's Precision Vaccines Program. To facilitate and accelerate these therapy and vaccination development efforts, more detailed immunophenotyping and understanding of the host immune response to SARS-CoV-2 are required. This knowledge may inform prognostication of resolution of infection versus disease progression and identify the relevant targets for potential therapeutic interventions. Overall, the outcomes of these immunophenotyping maps are critical for identifying and prioritizing host-directed interventions to limit or mitigate disease progression. Based on this rationale, we hypothesize that plasma proteomics and metabolomics from hospitalized COVID-19 patients, longitudinally collected during the hospital stay and during the subsequent convalescence period of up to one year post-discharge from the hospital will provide much needed insights into the intricacies of the immunophenotype of COVD19 patients. Thus, they will be crucial to support NIAID's efforts towards enabling and accelerating therapy and vaccine development. To this end, we propose a Proteomics and Metabolomics Core (PMC) to support NIAID's efforts to characterize at the molecular and cellular level the immunophenotype associated with COVID-19. The PMC will quantitative map the global plasma proteome (Specific Aim 1) and the global plasma metabolome (Specific Aim 2), followed by hypothesis-driven targeted metabolomics to detect metabolites and metabolic pathways that play a role in the COVID-19 disease progression (Specific Aim 3). All plasma samples will be longitudinally collected from COVID-19 patients upon hospitalization and the following 28 days in the hospital as well as the subsequent convalescence period of up to 12 months after discharge. We anticipate that the PMC will make substantial contributions to confronting the new COVID-19 pandemic, for which therapeutic strategies and vaccines must be developed rapidly. The PMC will help portray a broad profile of the changes that occur in COVID-19 patients and that are associated with disease severity, progression and recovery to support the quest for anti-COVID-19 therapies and vaccines.