Therapeutic Effectiveness of Interferon-α2b Against COVID-19: The Cuban Experience

Pereda, Ricardo; González, Daniel; Rivero, Hubert Blas; Rivero, Juan; Pérez, Albadio; Lopez, Lissette del Rosario; Mezquia, Natacha; Venegas, Rafael; Betancourt, Jaime; Domínguez, Rodolfo Emilio

doi:10.1089/jir.2020.0124

Cited by 36 publications

(28 citation statements)

References 16 publications

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“…A prospective observational study was conducted to assess the therapeutic efficacy of IFN-a2b in SARS-CoV-2 patients during the first month after the COVID-19 outbreak began in Cuba. Intramuscular administration of IFN-a2b improved both the rate of recovery and case fatalities (91). However, a retrospective cohort study demonstrated that there is great importance on the timing of administration of IFN-a2b with reduction of in-hospital mortality when administered the first five days of admission but increased mortality and delayed recovery was seen if given later (92).…”

Section: Canonical and Non-canonical Ifn Signaling In Antiviral Respomentioning

confidence: 99%

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

et al. 2020

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For several decades there has been accumulating evidence implicating type I interferons (IFNs) as key elements of the immune response. Therapeutic approaches incorporating different recombinant type I IFN proteins have been successfully employed to treat a diverse group of diseases with significant and positive outcomes. The biological activities of type I IFNs are consequences of signaling events occurring in the cytoplasm and nucleus of cells. Biochemical events involving JAK/STAT proteins that control transcriptional activation of IFN-stimulated genes (ISGs) were the first to be identified and are referred to as “canonical” signaling. Subsequent identification of JAK/STAT-independent signaling pathways, critical for ISG transcription and/or mRNA translation, are denoted as “non-canonical” or “non-classical” pathways. In this review, we summarize these signaling cascades and discuss recent developments in the field, specifically as they relate to the biological and clinical implications of engagement of both canonical and non-canonical pathways.

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Section: Canonical and Non-canonical Ifn Signaling In Antiviral Respomentioning

confidence: 99%

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

et al. 2020

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“…The therapeutic Cuban protocol has included IFN-a (IFN alpha 2b, Heberon ALFA R, Cuba) therapy even though it is currently evaluated in clinical trials for COVID-19 patients (see at https:// rpcec.sld.cu/). The first results have been reported by Pereda et al (101), and although it was not a randomized clinical trial rather a retrospective analysis with a small control group of patients with no IFNa treatmentthe major outcomes were a reduction in time needed to obtain a negative qRT-PCR and more satisfactory recovery of treated patients. The abovementioned pieces of evidences suggest that type I IFN can be used both as, therapeutic as well as prophylactic agents against SARS-CoV-2.…”

Section: Type I Ifns: Preclinical and Clinical Studiesmentioning

confidence: 99%

“…Retrospective studies of COVID-19 patients treated with type I IFNs could help document the evidence of IFN effect in patients with and without comorbidities, specifically regarding easy-torecord clinical and laboratory parameters, all of which would support the wide range of IFNs effects beyond their antiviral and immunomodulatory roles. The shreds of evidence concerning the extensive therapeutic use of IFN-a in Cuba, as part of the national treatment guideline during the COVID-19 pandemic, demonstrate a significant reduction in the number of patients progressing to severe forms of COVID-19 (101).…”

Section: Ace2 Depletion Elicits Serious Pathological Events In Severementioning

confidence: 99%

Revisiting Pleiotropic Effects of Type I Interferons: Rationale for Its Prophylactic and Therapeutic Use Against SARS-CoV-2

et al. 2021

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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.

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“…In these trials, the efficacy of IFN was more marked when administered early during the disease course. In addition, investigators from Cuba also presented (pre-published) encouraging data on the use of IFN-α-2b by subcutaneous route in a prospective observational study, but this study contained several confounders which were not corrected by multivariable analysis (Pereda et al, 2020).…”

Section: Impact Of Type I Interferon Subcutaneous Injections On Covidmentioning

confidence: 99%

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b–Literature Review and Personal Preliminary Experience

et al. 2020

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The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7–16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.

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Therapeutic Effectiveness of Interferon-α2b Against COVID-19: The Cuban Experience

Cited by 36 publications

References 16 publications

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signaling Pathways

Revisiting Pleiotropic Effects of Type I Interferons: Rationale for Its Prophylactic and Therapeutic Use Against SARS-CoV-2

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b–Literature Review and Personal Preliminary Experience

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