A cluster of respiratory illness that emerged in December, 2019 in Wuhan China marked the arrival of novel coronavirus Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. SARS-CoV-2 infection presents with a spectrum of symptoms, ranging from asymptomatic, to malaise, myalgias, and cough. Approximately 15% of patients will go on to develop severe disease consistent with characterized by pneumonia, with hypoxemia and multi-lobar ground glass opacities on chest CT scan. Many of these patients with severe disease will require ICU care, develop Acute Respiratory Distress Syndrome (ARDS), shock, multisystem organ failure, and superinfections. Extra-corporeal membrane oxygenation (ECMO) may be required to sustain life. Preliminary estimates from the US and China find that older age and underlying co-morbidities such as Chronic Obstructive Pulmonary Disease (COPD), ischemic heart disease, diabetes mellitus, and immunosuppression are associated with increase mortality in COVID-19. However, morbidity and mortality may also occur in younger patients. While anti-viral agents are being studied in randomized controlled trials, there is increasing use of off-label host and pathogen-directed therapies outside of controlled clinical trials and with little to no scientific evidence supporting their use. The research proposed here is “a prospective cohort study to assess longitudinal immune responses in hospitalized patients with covid-19.” This study is a multi-site study coordinated through the NIH NIAID Division of Allergy, Immunology, and Transplantation. The study will use immunophenotyping of host factors that have the potential to predict viral clearance or risk of prolonged viral replication and measures associated with clinical decline versus resolution of COVID-19 and its sequelae. These studies are critical for identifying potential targets and timing for host-directed therapeutic interventions. Understanding host immune response kinetics and phenotypes as they relate to clinical illness will assist in prioritizing trials of host-targeted interventions and treatments to limit or mitigate disease progression and recovery from illness. OHSU is participating as one site in this observational multi-site cohort study of hospitalized COVID-19 patients that will prospectively collect clinical, laboratory, and radiographic patient data in coordination with collection of blood samples and respiratory secretions in order to identify immunophenotypic and genomic features of COVID-19 across the spectrum of disease in hospitalized patients. Subjects will subsequently be followed for up to a year post-infection with interval histories and specimen collection and analysis. Results of this research are expected to help to prioritize interventions and/or optimize timing for administration of host-response directed therapeutics