Although the airways represent a focus of COVID-19 infection and immediate threat to the host, the virus can disseminate systemically and have a profound impact on the body. While epithelial and endothelial cells are the major targets of viral infection through expression of the ACE2 receptor [13,14] innate and adaptive immune responses of the host contribute critical resistance and pathogenic responses at all stages of disease. Effector cells of the Mononuclear Phagocyte System (MPS), whether they become infected [15] or not, depend mostly on recruitment of bone marrow-derived monocytes to tissues [16], [17], [18] rather than resident macrophages of embryonic origin [16,19]. Mononuclear phagocytes collaborate with other immune and non-immune pathways to mediate local and systemic anti-viral resistance and recovery, while also promoting morbidity and mortality. The MPS is a major contributor to the hyperinflammatory and procoagulant secretion syndrome, as demonstrated in earlier SARS syndromes as well as COVID-19 infection [20]. Ready access to peripheral blood samples from those at risk, provides a window on the dynamics of infection and their monocyte activation status, a guide to clinical diagnosis, treatment and prevention.