As is well-known now, the coronavirus can get into cells of lungs in an endosomny way or by participation of a sincytium. Destruction of alveolar cells where there are ACE-2-receptors, can be started by virus replication which leads to a lysis of a cell, or the antigen-antibody complex causing an antitelozavisimy cellular tsitoksichnost through activation of a system of a complement. For this reason the subject of participation of a complement in a pathogeny of COVID-19 draws more and more attention recently.
Activation of a system of a complement can lead to splitting on fragments of C3a and C5a operating as anaphylotoxins and chemotaxins, activating neutrophils, monocytes, macrophages and eosinophils in targetny fabric. After the attack effector mediators, free radicals, active short-lived forms of oxygen can release these cells (superoxide). Besides, the complement activation involving C5 convertase leads to linking of proteins of C5b-C8 and formation of a membranotakuyushchy complex with further pass of C9 to the channel of a complex and crossing of a cell membrane of an alveolar epithelium that leads to osmotic damage of a cell and its death.
To estimate a role of a system of a complement in COVID-19 pathobiology, it should be noted cases of recovery of patients of intensive care unit with pneumonia or with acute respiratory a distress syndrome against the background of heavy COVID-19, as a result of receiving drug by them ekulizumab, being an antibody against C5 convertase. This drug prevents formation of a membranoatakuyushchy complex and, therefore, antitelozavisimy cellular cytotoxicity.
Ekulizumab was approved by Management on health control of quality of foodstuff and medicines of the USA (FDA). Where the pathogenic antibody interacts with antigen, initiation of involvement of C5b-C8 is required that finally comes to an end with formation of a membranoatakuyushchy complex with participation of C9 which forms a time and destroys integrity of a cellular membrane that vedt to death of a cell. Eskulizumab shows the efficiency at treatment of a syndrome of hemolitic anemia, a paroxysmal night gemoglobinurimiya, heavy myasthenia and other pathology. Early purpose of an eskulizumab is aware of treatment can shed finally light on influence of a way of a complement on weight of a course of a koronavirusny infection in distal department of a bronchopulmonary system.
Besides, studying of a phenomenon of a tsitokinovy storm at COVID-19 continues. SILT-6 cytokine is raised approximately at 36% of patients with an easy current of COVID-19, and at seriously ill patients increase in this pro-inflammatory cytokine is observed already in 76% of cases. Actually, patients with COVID-19 are characterized as heavy at increase in IL-6, IL-2 cytokines, a factor of a necrosis of a tumor of TNF, a monocytic chemotactic factor of MCP-1, MIP-1A, IL-10, IL-7 cytokines and a granulotsitarny colony stimulating factor of G-CSF, especially it concerns patients of the intensive care unit. Further, the syndrome of release of cytokines or a tsitokinovy storm was confirmed with increase in level of SILT-6 cytokine in connection with COC3.
Possibly, the most typical laboratory find at patients with the confirmed COVID-19 can be considered the lymphopenia which is potentially signaling about extensive distribution of SARS-CoV-2. The alternative explanation consists that the lymphopenia can arise because of emission of cortisol as a result of a stress. Binding of lymphocytes in lungs can be one more hypothesis (only 3-5% of mononuclear cells are in circulation). Despite a lymphopenia, at patients, especially, heavy, activation of lymphocytes is in the same way observed.
In a pulmonary interstitium domination of CD8 lymphocytes is noted that is considered as key permission of SARS-CoV-2. However, the accompanying increased level of SILT-6 and SILT-8 cytokines interferes with ability of T-cells to interact with dendritic cells against a virus, and also limits makrofagealny clearance of pathogens. In this COVID-19 it is similar to MERS which is also characterized by the increase in level of circulation of SILT-8 lowered by production and processing of anti-virus cytokines, such as interferona of the 1st type (interferona an alpha and a beta).
Thus, it is possible to draw a conclusion that further studying of reaction of a system of immunity in response to SARS-CoV-2 can give us the answer to a question how effectively to treat a new koronavirusny infection.