Interferon system for COVID-19

SARS-CoV-2 is the causative agent of COVID-19 and infects the respiratory tract, blood cells, gastrointestinal tract, kidneys, liver, heart, brain and other organs. The ability of SARS-CoV-2 to escape from immune surveillance leads to deregulation of the immune response, cytokine storm and extensive tissue damage to infected organs. It is assumed that the pathogenesis of the deterioration of the course of COVID-19 is much more complicated and one of the mechanisms for the escape of SARS-Cov-2 from the influence of innate immunity is the inhibition of signaling pathways for the production and action of interferon (IFN). This review summarizes the role of the IFN system in SARS-CoV-2 infection and discusses the sophisticated mechanisms that coronaviruses have developed over the course of evolution to evade immune surveillance and suppress IFN responses. The IFN-related issues of counteraction to SARS-Cov-2 infection and the IFN-dependent adverse course of COVID-19 is also discussed.

[The problem of the use of interferons in the novel coronavirus disease COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus)].

By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the Google Scholar preprint database using the available search queries «MeSH for coronavirus¼, «SARS-CoV-2¼, «IFN drugs¼, and «COVID-19¼. Interferon therapy is indicated for early administration (within the first 5 days of patient admission) in cases of mild to moderate COVID-19 to take advantage of the narrow therapeutic window of IFNs action. Control and suppression of viral replication requires therapy with IFNs and other effective antiviral agents that inhibit the reproduction of SARS-CoV-2 and induce several interferon-stimulated genes (ISG). Type I IFNs (IFN-I) exhibit potent pro-inflammatory properties and activate a wide variety of different cell types that respond to IFNs stimulation and pathogen entry. IFN-III confer local mucosal antiviral immunity without inducing the strong systemic pro-inflammatory responses associated with IFN-I. The use of IFNs drugs in the therapy of new coronavirus infection requires a cautious and differentiated approach, because in severe cases they can aggravate viral pathogenesis by causing excessive intensity of inflammatory reactions. The unique biological properties of substances of this class allow us to consider them as therapeutic agents with significant potential for use in patients with COVID-19.

[Interferon gamma in the treatment of patients with moderate COVID-19].

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.