COVID-19 rapidly emerged as a crippling public health crisis in the last few months, which has presented a series health risk . Understanding of the immune response and biomarker analysis is needed to progress toward understanding disease pathology and developing improved treatment options . The goal of this study is to identify pathogenic factors that are linked to disease severity and patient characteristics . Patients with COVID-19 who were hospitalized from March 17 to June 5, 2020 were analyzed for clinical features of disease and soluble plasma cytokines in association with disease severity and sex . Data from COVID-19 patients with acute illness were examined along with an age- and gender-matched control cohort . We identified a group of 16 soluble factors that were found to be increased in COVID-19 patients compared to controls, whereas 2 factors were decreased . In addition to inflammatory cytokines, we found significant increases in factors known to mediate vasculitis and vascular remodeling (PDGF-AA, PDGF-AB-BB, soluble CD40L (sCD40L), FGF, and IP10). Four factors such as platelet-derived growth factors, fibroblast growth factor-2, and IFN-γ-inducible protein 10 were strongly associated with severe disease and ICU admission . Th2-related factors (IL-4 and IL-13) were increased with IL-4 and sCD40L present at increased levels in males compared with females . Our analysis revealed networking clusters of cytokines and growth factors, including previously unknown roles of vascular and stromal remodeling, activation of the innate immunity, as well activation of type 2 immune responses in the immunopathogenesis of COVID-19 . These data highlight biomarker associations with disease severity and sex in COVID-19 patients.