COVID-19 Immunophenotyping Proteomics and Metabolomics Core (PMC)

Project Summary/AbstractIn Dec 2019, a cluster of respiratory illness in Wuhan China defined the onset of a worldwide pandemic involvinga novel coronavirus (SARS-CoV-2). SARS-CoV-2 infected patients are frequently asymptomatic, but initialepidemiologic estimates from the WHO indicate that ~15% of patients develop severe disease including viralpneumonia often requiring ICU care due to progression to develop life-threatening complications including (butnot limited to) shock and secondary organ failures, and super-infections. Risk factors for increased mortality fromCOVID-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 effortshave been launched towards the development of anti-SARS-CoV-2 vaccines, including those within BostonChildren's Hospital's Precision Vaccines Program. To facilitate and accelerate these therapy and vaccinationdevelopment efforts, more detailed immunophenotyping and understanding of the host immune response toSARS-CoV-2 are required. This knowledge may inform prognostication of resolution of infection versus diseaseprogression and identify the relevant targets for potential therapeutic interventions. Overall, the outcomes ofthese immunophenotyping maps are critical for identifying and prioritizing host-directed interventions to limit ormitigate disease progression. Based on this rationale, we hypothesize that plasma proteomics and metabolomicsfrom hospitalized COVID-19 patients, longitudinally collected during the hospital stay and during the subsequentconvalescence period of up to one year post-discharge from the hospital will provide much needed insights intothe intricacies of the immunophenotype of COVD19 patients. Thus, they will be crucial to support NIAID's effortstowards enabling and accelerating therapy and vaccine development. To this end, we propose a Proteomics andMetabolomics Core (PMC) to support NIAID's efforts to characterize at the molecular and cellular level theimmunophenotype 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 metabolicpathways that play a role in the COVID-19 disease progression (Specific Aim 3). All plasma samples will belongitudinally collected from COVID-19 patients upon hospitalization and the following 28 days in the hospital aswell 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, forwhich therapeutic strategies and vaccines must be developed rapidly. The PMC will help portray a broad profileof the changes that occur in COVID-19 patients and that are associated with disease severity, progression andrecovery to support the quest for anti-COVID-19 therapies and vaccines.