Congenital and Acquired Interferonopathies: Differentiated Approaches to Interferon Therapy

This chapter reviews various interferon (IFN) system disturbances—interferonopathies. The authors describe clinical specifics of type I interferonopathy associated with overexpression of IFNα—which is a rare Mendelian genetic disease. Certain autoimmune diseases (systemic lupus erythematosus (SLE), vasculitis, immune dysregulation syndrome, etc.) are also characterized by overproduction of IFNα. Furthermore the most common interferonopathies are described—deficiencies of IFN, congenital or acquired IFNα/IFNβ and IFNγ deficiencies in children and adults. Deficiency of IFNα/IFNβ associated with severe recurrent viral infections and deficiency of IFNγ cause mycobacterial infection. Interferon-corrective therapy methods are described. The target therapy of type I interferonopathies (biologics) binds IFNα and normalizes the high level of IFNα. From the other side, patients with congenital IFNα deficiencies are needed in replacement IFN therapy. In case of acquired IFNα deficiency, the differentiated interferon-corrective therapy is performed. In both replacement and interferon-corrective therapies, recombinant human IFNα2b in complex with antioxidants (Viferon®) can be used, because their application is safe and has good clinical efficiency and no side effects

Remodeling of Phenotype CD16 + CD11b + Neutrophilic Granulocytes in Acute Viral and Acute Bacterial Infections

Neutrophilic granulocytes (NGs) are very important cells of innate immunity that can very quickly realize antibacterial and antiviral defense. Until the present time, the phenomenon of different levels of presentations of membrane receptors CD16 and CD11b NG in normal and pathological conditions wasn’t studied. We had studied the population of CD16+CD11b+NG in two groups of patients with acute viral and acute bacterial infections in the models of acute bacterial tonsillitis (ABT) and acute viral tonsillitis-EBV infection (AEBVI), having the same clinical symptoms in early stages of the disease. Comparative analysis of the redistribution of equipment intensity of CD16 and CD11b has detected three subpopulations of CD16+CD11b+NG population—CD16brightCD11bbright, CD16brightCD11bdim, and CD16dimCD11bbright—in normal and pathological conditions. It was found that subpopulation CD16brightCD11bdimNG dominates in healthy individuals; subpopulation CD16brightCD11bbrightNG dominates in patients with acute viral infection; subpopulation CD16dimCD11bbrightNG dominates in patients with acute bacterial infections. We had demonstrated that the study of CD16+CD11b+NG subpopulations allows in early stage of diseases to diagnose acute viral and acute bacterial infections. Our studies have demonstrated the positive effects of eukaryotic DNA sodium salt on the negatively altered phenotype subpopulation CD16+CD11b+NG, in particular, through the remodeling of the expression of CD11b on NG membrane

INTEGRATION DIAGNOSTIC CRITERION FOR EVALUATION OF THE SEVERITY OF COVID-19 AND THE RISK OF POST-COVID SYNDROME

The pathophysiology of severe COVID-19 is characterized by changes in the number, phenotype, and function of neutrophil granulocytes (NG). Among the effector antiviral mechanisms of NC, neutrophil extracellular traps (NETs) are one of the most important, but their excessive formation exacerbates inflammation in acute respiratory distress syndrome and contributes to microvascular thrombosis. Their detection and quantification may be important in various forms of the course of COVID-19 to determine the correlation with the outcome of the disease, assess the risk of developing post-COVID syndrome, and possibly monitor future targeted therapy.Purpose of the study: to develop a new diagnostic integration criterion to assess the severity of COVID-19 and the risk of complications in the post-COVID period, including post-COVID syndrome in peripheral blood.Materials and Methods: Peripheral blood (PB) samples were studied from 31 patients with acute COVID-19 (moderate (n=15) and severe (n=16)), 52 patients discharged from the hospital after severe COVID-19 treatment severity, in terms of 30 to 60 days, with post-COVID syndrome (PCS) and 100 healthy volunteers. The parameters of the general clinical blood test (MicroCC-20Plus) were evaluated, the leukocyte formula was calculated in PC smears, taking into account the number of formed NETs and NGs that went into pathological apoptosis. Based on the obtained results, an integration diagnostic criterion was calculated using the formula:.Results. A decrease in IDC was shown in the moderate course of the disease by 8,5 times (p<0,05), and in severe cases by 30 times(p<0,05) compared with the values in the group of healthy individuals. It was also found that in 88,5% of patients with PCS who underwent SARS-CoV-2, no morphologically pathologically altered NG were detected in the PB. At the same time, in 11.5% of patients with PCS, the appearance of NETs and cells with pathological apoptosis was noted, while the IDC of NG-PCS was 8 times less than in the comparison group and did not differ from the parameters of patients with moderate COVID-19 (p>0,05), which dictates the need for further dispensary observation of such patients.Conclusion. The data obtained in this study indicate that the developed integration diagnostic criterion allows us to assess both the severity of COVID-19 in the acute period and the risk of post-COVID syndrome. It should be emphasized that the characteristic changes in NG detected in COVID-19 can be easily identified in PB and consistently monitored by the calculated integral diagnostic criterion. A significant decrease in IDC indicates the persisting hyper activation of NG and the need for targeted immunotherapy aimed at modulating NG dysfunctions