Abstract
The pandemic distribution of SARS-CoV-2 together with its particular feature of inactivating the interferon-based endogenous response and accordingly, impairing the innate immunity, has become a challenge for the international scientific and medical community. Fortunately, recombinant interferons as therapeutic products have accumulated a long history of beneficial therapeutic results in the treatment of chronic and acute viral diseases and also in the therapy of some types of cancer. One of the first antiviral treatments during the onset of COVID-19 in China was based on the use of recombinant interferon alfa 2b, so many clinicians began to use it, not only as therapy but also as a prophylactic approach, mainly in medical personnel. At the same time, basic research on interferons provided new insights that have contributed to a much better understanding of how treatment with interferons, initially considered as antivirals, actually has a much broader pharmacological scope. In this review, we briefly describe interferons, how they are induced in the event of a viral infection, and how they elicit signaling after contact with their specific receptor on target cells. Additionally, some of the genes stimulated by type I interferons are described, as well as the way interferon-mediated signaling is torpedoed by coronaviruses and in particular by SARS-CoV-2. Angiotensin converting enzyme 2 (ACE2) gene is one of the interferon response genes. Although for many scientists this fact could result in an adverse effect of interferon treatment in COVID-19 patients, ACE2 expression contributes to the balance of the renin-angiotensin system, which is greatly affected by SARS-CoV-2 in its internalization into the cell. This manuscript also includes the relationship between type I interferons and neutrophils, NETosis, and interleukin 17. Finally, under the subtitle of “take-home messages”, we discuss the rationale behind a timely treatment with interferons in the context of COVID-19 is emphasized.
Highlights
Severe acute respiratory syndrome (SARS) is an infectious disease of this century caused by coronaviruses (SARS-CoV and SARS-CoV-2) that leads to pulmonary and other systemic pathological conditions [1,2,3]
Other IFN-stimulated genes (ISGs) associated with SARS-CoV-2 pathogenicity are Cholesterol-25hydroxylase (CH25H) which converts cholesterol to a soluble antiviral factor and is a potent SARS-CoV-2 inhibitor [46], and the type I IFN-inducible transmembrane protein family (IFITM), that during SARS-CoV-2 infection may paradoxically act as an entry cofactor in human lung cells [47]
Disrupted balance of renin–angiotensin system (RAS) in the COVID-19 context implies that the excess of angiotensin II (Ang II), secondary to decreased Angiotensin converting enzyme 2 (ACE2) levels, causes pulmonary vasoconstriction, inflammation, cytokine-induced organ damage [131], increased membrane permeability [132], and epithelial cell apoptosis [133]
Summary
Severe acute respiratory syndrome (SARS) is an infectious disease of this century caused by coronaviruses (SARS-CoV and SARS-CoV-2) that leads to pulmonary and other systemic pathological conditions [1,2,3]. Among the strengths of the latter, the early administration of interferon alpha 2b (IFNa2b) (Heberon Alfa R, Cuba) could has contributed to the effective control of COVID-19 in Cuba reducing the high incidence of severe cases and mortality (see covid19cubadata.github.io/#cuba). This IFNa2b-based treatment was used on patients suffering COVID-19 symptoms, and on their asymptomatic confirmed and suspected epidemiological contacts, as well as on health professionals at risk [7]. The present review is intended to analyze the contribution of IFN-a therapies in the context of SARS-CoV-2 on the rationale of molecular biology, genetics, and the immune response elicited by IFNa2b. We expect that this review will help scientists and clinicians on the Covid-19 battlefield to understand and systematize their knowledge about interferons
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