Lippi G, et al. Ann Transl Med 2020 - Review.
Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine. Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature's virtually perfect biological weapon. This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease. It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different molecular and biological mechanisms. The disease can hence be divided in at least five different phases (incubation, respiratory, pro-inflammatory, pro-thrombotic, and death or remission). Whilst the virus triggers direct cytopathic injury during the initial stage of illness, in the following evolving phases, it is the host itself that undergoes an almost suicidal reaction, sustained, amplified and maintained by the immune, complement and hemostatic systems. Another peculiar property making SARS-CoV-2 a devious and vicious pathogen is the biophysical structure of its receptor biding domain, which needs to be primed by human proteases, thus being less efficiently targetable by the host immune system. The unique pathophysiology of COVID-19 requires the customization of therapy by individual patient characteristics and according to the phase-specific, evolving derangement of the multiple biological pathways.