Transformation of classic inflammation in COVID-19 into systemic inflammation with the formation of a vicious pathogenetic circle. Three key mechanisms may be distinguished in the formation of a vicious pathogenetic circle and the development of a critical state in COVID-19: (1) the severity of ARDS (Acute Respiratory Distress Syndrome), which is linked to acute lung damage and systemic microcirculatory abnormalities, regardless of the primary focus of damage. Additionally, with the development of other resuscitation syndromes such as DIC and MODS, the phenomenon of systemic change promotes the onset of organ dysfunctions and coagulopathy. (2) During the development of microcirculatory diseases, DAMPs (damage-associated molecular pattern) and TF (Tissue Factor) and other hazardous products of tissue degradation are widespread. (3) The emergence of the “cytokine storm” phenomenon, which is linked to hemophagocytic lymphohistiocytosis (macrophage activation syndrome, MAS) and overproduction of cytokines in the focus of COVID-19 canonical inflammation, sharply increases with the generalization of pro-inflammatory tissue stress linked to SI.