A re-appraisal of thrombogenesis in COVID-19, seen as a multiple Complex System

The aim of this essay is to re-consider the peculiar type of thrombogenesis observed in severe cases of COVID-19 infection, focusing on the multiple interconnected networks involved, such as inflammation, blood coagulation, fibrinolysis, and immune responses. These linked mechanisms can be assimilated to the “Complex Systems” (CS), that play a capital role in various domains: from physics to chemistry, biology and medicine, to social and behavioral sciences. CS are characterized by eliciting variable responses: their final results can be contradictory and often unpredictable. In fact, in severe COVID-19 various outcomes can occur, such as macro- and micro-thrombosis, vasculitis, hemorrhage, hyper and hypo fibrinolysis, distorted inflammatory and immune response, and others. The insight supplied by the CS theory in understanding thrombogenesis in COVID-19 can be useful in several ways. It recalls the importance of a “holistic” view of multiple patterns of signs, symptoms and biomarkers; stresses the added value of global versus mechanistic tests, particularly in coagulation and fibrinolysis; suggests building up small trials of selected patients in a perspective of precision medicine; discourages passive transfer of therapeutic choices from no- COVID to COVID patients; and finally indicates that some treatments, as the anti-inflammatory and the anti-coagulant ones, should be initiated as early as possible, so to avoid worsening of the condition by repetitive feedback and shortcut mechanisms.