Abstract: Recent literature on SARS-CoV-2 pathogenesis has suggested that the induction of substantial acute respiratory distress phenotypes is driven by a mismatched inflammatory response together with broad vascular dysfunction. While several detailed reports implementing multi-omic approaches have provided insight into the immune cell phenotypes involved in these processes, risk stratifying markers specific to COVID-19 and the vasculature have not been explored. Provided herein is a comprehensive, multi-omics-based description of the molecular antecedents to COVID-19 mortality, yielding new insights pertaining to the vasculature while highlighting the urgent need for clinical translation of novel biomarkers for disease prognosis.