MECHANISMS OF CYTOKINE STORM DEVELOPMENT IN COVID-19 AND NEW POTENTIAL TARGETS OF PHARMACOTHERAPY

The development of a "cytokine storm", characteristic severe COVID-19 forms, can be defined as state uncontrolled release large number inflammatory mediators. attachment SARS-CoV-2 S-glycoprotein to angiotensin-converting enzyme 2 is considered process that triggers complex molecular interactions lead hyperinflammation. In its turn, it realized through several systems: renin-angiotensin-aldosterone, kallikrein-kinin and complement system. Knowledge these mechanisms suggests potential therapeutic interventions targeted by existing agents counter the cytokine storm treat acute respiratory distress syndrome associated with COVID-19. aim review article summarize currently known data on processes underlying storm" in patients COVID-19, possible options for their pharmacological correction. Materials methods. base was represented such systems Medline, Cochrane Central Register Controlled Trials, Scopus, Web Science Core Collection, Library, ClinicalTrials.gov, Elibrary, Google-Academy. A search carried out following keywords combinations: renin-angiotensin-aldosterone system, bradykinin, hyaluronic acid, pharmacotherapy. Results. mediated pathogenetic changes body response penetration into cell. RAAS, suppression ACE2 leads decrease ability degrade ATII, which, one hand, amount AT1-7, and, other effect ATII AT1R subsequent vasoconstriction lung damage. disturbances system are associated, increased expression kallikrein an increase formation bradykinin metabolite des-Arg 9-bradykinin. On C1-esterase inhibitor which prevents kallikrein, impaired inactivation 9-bradykinin under action ACE 2. nucleocapsid protein activation lectin pathway. It production anaphylatoxins C3a C5a, stimulate synthesis pro-inflammatory cytokines. Proinflammatory cytokines potent inducers HAS gene endothelium, encodes membrane enzymes hyaluronate synthase. sweating fluid alveoli caused "bradykinin combination overproduction accumulates water 1000 times own mass, dense jelly-like substance gas exchange. Conclusion. Promising areas pharmacotherapy impact dysfunction listed above systems. However, efficacy safety most drugs treatment studied carefully designed clinical trials.