Interferons in the Therapy of Severe Coronavirus Infections: A Critical Analysis and Recollection of a Forgotten Therapeutic Regimen with Interferon Beta

Abstract

<jats:title>Abstract</jats:title><jats:p>The pharmacological and immunological properties of interferons, especially those of interferon beta, and the corresponding treatment strategies are described, and the results of studies with different interferons in coronavirus infections are analysed. Furthermore, the data obtained with high-dosed native interferon beta in life-threatening acute viral diseases as well as the results of clinical pilot studies with high-dosed recombinant interferon beta-1a are provided because they serve as the rationale for the proposed therapeutic regimen to be applied in acute viral infections. This regimen differs from those approved for treatment of multiple sclerosis and consists of interferon beta-1a administered as a 24 hour intravenous infusion at a daily dose of up to 90 µg for 3–5 consecutive days. Since under this regimen transient severe side effects can occur, it is analysed which patients are suitable for this kind of treatment in general and if patients with severe coronavirus infections could also be treated accordingly.</jats:p>

In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection

“…Therefore, this cytokine could be involved in the activation of protective immunity in this group. Corroborating this prominent activation of a mucosal immune response, it was found a significant positive correlation between IFN-α and IFN-β, which, in accordance to described above, both of these cytokines are involved in the protection against the virus infection (16,47,48).…”

“…In the literature, there is a handful of data that shows the role of interferons in the coronavirus infection. The main findings evidenced that both type I interferon (IFN-α and IFN-β) and type II interferon (IFN-γ) levels raised after MERS-CoV and SARS-CoV infection, in order to induce a host defense mechanism against virus due to its strong capacity to inhibit the replication of coronaviruses ( 16 , 47 , 48 ). According to the review published by Jafarzadeh et al ( 49 ), in SARS-CoV-2 infection, the IFNs response in the upper airways, in a general way, is able to drive to the viral elimination accompanied or not with mild/moderate symptoms.…”

“…Interestingly, IL-10 showed significant positive correlations only with IFN-α and IFN-γ, but not with IFN-β. Although these data should be analyzed with care, the lack of correlation between IL-10 and IFN-β can putatively indicate that the IFN-β release was not impacted by the IL-10 in order to guarantee an appropriate mucosal immune response against the SARS-CoV-2 infection in this group, since IFN-β, due to its stronger hydrophobicity, has a superior capacity to inhibit coronavirus replication than the other interferons ( 47 ).…”

Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons Between Candidate Anti-Coronavirus Compounds

“…There are five compound classes targeting host processes, including host protease inhibitors [39][40][41][42][43][44], endosomal trafficking inhibitors [45][46][47][48][49], interferons [50][51][52][53][54][55], compounds reported to stimulate host immunity or induce interferon [56,57], and compounds that influence miscellaneous additional host processes [58,59]. Finally, there are two additional treatment categories -convalescent plasma [60,61] and compounds that have uncertain mechanisms of action.…”

“…Interferons Interferons (IFNs) have been extensively studied for their ability to inhibit each of the pandemic coronaviruses in cell culture, animal models, and/or clinical studies [54]. SARS-CoV-2 may be more susceptible to interferons than SARS-CoV [55] IFN- and IFN- consistently demonstrate coronavirus inhibitory activity in cell culture and in animal models, although the timing of administration is likely to be critical as late administration may contribute to immunopathology [50,51]. IFN- has generated recent interest because it acts at epithelial barriers and has been reported to cause less inflammation than IFN- and IFN- [52,53].…”