Pathogenetic bases of the use of antifibrotic therapy with Bovhyaluronidazum azoximerum in patients with new coronavirus infection COVID-19

Abstract

One of the most likely and serious complications of the novel coronavirus infection (COVID-19) is pneumofibrosis, which can negatively affect the duration and quality of life of patients who have suffered from this disease. The appearance of fibrotic changes in COVID-19 is due to a number of pathological processes that occur in the lungs after the pathogen, the SARS- CoV-2 virus, enters there. First of all, an inflammatory response is triggered, which is mediated by macrophages and granulocytes, due to which the synthesis of pro-inflammatory cytokines, incl. IL-1, TNF, which are potent inducers of hyaluronic acid synthetase. There is a  decrease in  the  content of  fibrinolysis activators in  the  pulmonary endothelium, which contributes to the  accumulation of fibrin in the vessels of the lungs. Fibrin can escape into the interstitial space and cause the formation of sclerosing alveolitis. The increasing defeat of pneumocytes favors the release of fibrin into the lumen of the alveoli, which causes the formation of hyaline membranes. The regulation of the fibrotic process involves immunocompetent cells, primarily CD4 + T-lymphocytes, which are capable of producing cytokines, chemokines and growth factors, and these, in turn, stimulate the proliferation and differentiation of  fibroblasts, as well as their production of  collagen. The  more severe forms of  infectious process can lead to the greater risk of developing fibrotic changes. Risk factors are a large area of lung damage, the use of artificial pulmonary ventilation, ARDS, fibrosis in anamnesis. An additional role in the pathomorphogenesis of pneumofibrosis is played by smoking, external inhalation effects (inhalation of organic and inorganic dust), gastroesophageal reflux, type II diabetes mellitus, genetic factors (familial idiopathic pulmonary fibrosis). The pathogenetic features of COVID-19 require administration of anti-fibrotic treatment. Bovhyaluronidazum azoximerum, a drug that is a conjugate of the proteolytic enzyme hyaluronidase, is considered as an antifibrotic agent. The treatment regimens with this drug recommended in the period of convalescence for patients who have undergone COVID-19 are given.