IMmunoPhenotyping Assessment of a Covid-19 Cohort (IMPACC): Immunophenotyping of innate and adaptive immune response to SARS-CoV-2 infection

LAS PROJECT SUMMARY:From a cluster of respiratory illnesses in Wuhan, China, to a worldwide pandemic, the world has learned of anovel coronavirus (SARS-CoV-2) but little is known about the pathogenesis that leads to the disease termed"COVID". Patients with SARS-CoV-2 infection range from asymptomatic, mild, moderate, to severe infections,resulting in ICU hospitalization and even death. In the US alone, there is a prediction of ~100,000 - 240,000deaths from SARS-CoV-2 infections. There is an urgent need to 1) characterize the host innate and adaptiveresponse to SARS-CoV-2 and 2) to define immunologic biomarkers that can inform new approaches fordiagnostic, prognostic, therapeutic and preventative (e.g., vaccine) modalities in order to improve our ability totreat and prevent disease.To enhance the efficiency of immuophenotyping, the Precision Vaccines Program (PVP) has optimized a numberof sample-sparing in vitro assays to characterize both innate and adaptive immune function. These establishedassays will be applied to the evaluation of SARS-CoV-2 infections and identification of biomarkers associatedwith morbidity and mortality, which remains an unmet need and a research priority for the fight against COVID.Through investigating soluble and cellular innate and adaptive immune mediators, we will gain insight into thecontrol of inflammation and infection in COVID. In Specific Aim 1 (SA1), we will measure, eg, (a) the plasmaenzyme adenosine deaminase (ADA) that metabolizes the anti-inflammatory metabolite adenosine to theimmunologically inert inosine, thereby enhancing Th1 immune responses and enhancing antiviral innate andadaptive immunity; and (b) human defensins, antimicrobial peptides that enhance innate antiviral (e.g., IFN) andneutralizing antibody (Ab) responses to coronaviruses. In SA2, we will employ system serology, to furthercharacterize Ab function and efficiency to SARS-CoV-2 across the severity of infection. In SA3, we will measureresponses of whole blood leukocytes to activation of pathogen recognition receptors (PRRs) as well asresponses of T-cell co-cultures to SARS-CoV-2 spike protein antigen.Overall, successful completion of the proposed IMPACC Local Assay Site studies will provide unique insightsinto human innate and adaptive immune responses to SARS-CoV-2 in relation to COVID progression andprognosis. These insights will provide fresh approaches to develop diagnostics, therapeutics and preventativemeasures against COVID-19, including vaccines.