UCSF COVID-19 Immunophenotyping Clinical Study and Core Laboratories

COVID-19, the pandemic illness caused by the novel virus SARS-CoV-2, is a serious respiratory illness thathas high infectivity and a mortality rate that varies from <1% to up to 20% depending on underlying risk factors.Indeed, disease severity varies markedly based on recognized clinical risk factors (age and co-morbidities).The biological underpinnings of this clinical variability are unknown but likely relate to variation in both the virusand the host response. A detailed understanding of the risk factors for severe disease, including genetic andenvironmental factors and the nature of the host immunological response, is essential for the development ofprognostic biomarkers and effective therapies. To meet this urgent need we propose to help develop and toparticipate in the IMPACC multi-center longitudinal clinical study of hospitalized patients with COVID-19 and toimmunophenotype participants using shared immunological methods that will be designed an carried out bycore laboratories at UCSF and at other participating institutions. Our specific aims are 1) to develop aprospective observational convenience cohort of adult subjects hospitalized with known or presumptiveCOVID-19, 2) to use this cohort to describe the relationship between specific immunologic assessments andclinical course of COVID-19 in hospitalized patients, and 3) to implement three core laboratories at UCSF tosupport immunophenotyping in this multicenter cohort. These core laboratories will perform bulk RNAsequencing of blood peripheral blood mononuclear cells (PBMC), bulk metagenomic next-generationsequencing (mNGS) on endotracheal aspirate samples, and serologic phage display assays (PhIP-Seq).Successful completion of these aims will yield critical information regarding the relationship between viral load,host immunological responses, and poor clinical outcomes that are urgently needed for biomarkerdevelopment and rational therapeutic targeting. In addition, the cellular samples banked in this study maydirectly contribute to the development of neutralizing antibodies and vaccine strategies that will be our ultimatedefense against recurrence of this extraordinary pandemic. A rapid and robust scientific and medical responseof the type proposed by the NIAID and the academic community in this consortium is an essential element of abroad response required to protect the health and well-being of all individuals, our health care system, and thebroader social structures that maintain global health and welfare.