About this Research Topic
SARS-CoV-2, in common with other viruses, limits the endogenous interferon (IFN) response to infection, encoding factors in its genome that block IFN production and dysregulate IFN-induced signaling networks. One of the main pathogenic elements of SARS-CoV-2 infection associated with an impaired IFN response, is increased production of chemokines in the absence of type I and III IFNs, that facilitates an exacerbated cytokine storm. Type I IFNs, IFN-αs/ß, have been used clinically as therapeutics for several decades, most notably the IFN-αs for the treatment of chronic hepatitis C virus infection. The scientific literature is replete with evidence that type I IFNs are the first line of defense following virus infection, specifically acute virus infections, and extensive pre-clinical data indicate that pre-treatment with type I or type III (IFN-λs) IFNs protects from subsequent viral challenge. During this unprecedented global pandemic, the importance of the type I/III IFN response in the context of preventing progression of COVID-19 to the severe, life-threatening hyper-inflammatory stage, has become evident. Accumulating data suggest that an early type I or type III IFN response is critical to viral clearance.
This Research Topic aims to highlight the importance of the IFN response during SARS-CoV-2 infection. The direct effects of type I and type III IFNs on inhibition of viral replication and on activation of the relevant innate immune response will be considered. In addition, the molecular mechanisms by which IFNs exert their inhibitory effects will be examined. Beyond pre-clinical evidence that IFNs contribute to clearance of SARS-CoV-2, the clinical evidence that type I and type III IFNs have utility for prevention of transmission when used for post-exposure prophylaxis and for treatment during the viral phase of COVID-19 will also be evaluated.
We welcome submissions of Original Research, Systematic Review, Review, Mini Review, Hypothesis and Theory, Perspective and Clinical Trial articles, which cover, but are not limited to, the following subtopics exploring the use of IFNs as prophylactics and therapeutics against SARS-CoV-2:
1) Early vs late administration of IFNs. Accumulating evidence indicates that early IFN treatment is warranted during the viral phase of COVID-19. The potential risks of late administration require clarification.
2) The anti-inflammatory properties of early IFN treatment. e.g. the role of IFN treatment in regulating a Th17 cell response and the mechanisms and roles by which IFNs regulate various innate immune cell populations – NK cells, neutrophils, macrophages, CD8+ T cells.
3) Possible differences in the prophylactic/therapeutic benefits among Type I, type II (IFN-γ) and type III IFNs. e.g. review of the WHO sponsored SOLIDARITY trial and other clinical trials that have evaluated the therapeutic potential of IFN-α2b, IFN-ß and IFN-γ.
4) Prophylactic IFN administration by systemic (subcutaneous, intramuscular) or mucosal (intranasal) routes. Dosing and durability of effects.
5) Effect of IFNs on increasing ACE2 levels. Risk-benefit balance.
6) Discussion of how therapeutic administration of type I/III IFNs may restore the SARS-CoV-2 blunted IFN response.
7) Potential of IFN treatment for the induction of an antiviral state: IFN effects on different stages of the viral replicative cycle.
8) Comparative IFN treatments in SARS-COV2 and other respiratory viruses.
9) Potential of IFN treatments in combination with anti-inflammatory biologics (Corticoids, anti-IL6R, Anti-IL1)
Topic Editor Dr. Rieux-Laucat received financial support from SANOFI. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Keywords: Interferons, Type I interferons, Type III interferons, antiviral status, SARS-CoV-2, COVID-19, ACE2, chemokines, cytokines, exogenous IFN delivery, antiviral state
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