Interferon Treatments for SARS-CoV-2: Challenges and Opportunities

Diya Jhuti, Angeli Rawat, Christina M Guo, Lindsay A Wilson, Edward J Mills, Jamie I Forrest, Diya Jhuti, Angeli Rawat, Christina M Guo, Lindsay A Wilson, Edward J Mills, Jamie I Forrest

Abstract

Interferon (IFN) therapies are used to treat a variety of infections and diseases and could be used to treat SARS-CoV-2. However, optimal use and timing of IFN therapy to treat SARS-CoV-2 is not well documented. We aimed to synthesize available evidence to understand whether interferon therapy should be recommended for treatment compared to a placebo or standard of care in adult patients. We reviewed literature comparing outcomes of randomized control trials that used IFN therapy for adults diagnosed with SARS-CoV-2 between 2019 and 2021. Data were extracted from 11 of 669 screened studies. Evidence of IFN effectiveness was mixed. Five studies reported that IFN was a better therapy than the control, four found no or minimal difference between IFN and the control, and two concluded that IFN led to worse patient outcomes than the control. Evidence was difficult to compare because of high variability in outcome measures, intervention types and administration, subtypes of IFNs used and timing of interventions. We recommend standardized indicators and reporting for IFN therapy for SARS-CoV-2 to improve evidence synthesis and generation. While IFN therapy has the potential to be a viable treatment for SARS-CoV-2, especially when combined with antivirals and early administration, the lack of comparable of study outcomes prevents evidence synthesis and uptake.

Keywords: COVID-19; Interferon; SARS-CoV-2.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study identification, screening and selection process

References

    1. WHO Solidarity Trial Consortium Repurposed antiviral drugs for Covid-19—interim WHO solidarity trial results. N Engl J Med. 2021;384:497–511. doi: 10.1056/NEJMoa2023184.
    1. Piper JM, Wen TT-S, Xenakis EM-J. Interferon therapy in primary care. Prim Care Update OBGYNS. 2001;8:163–169. doi: 10.1016/S1068-607X(00)00082-2.
    1. Blanco-Melo D, Nilsson-Payant BE, Liu W-C, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181:1036–1045.e9. doi: 10.1016/j.cell.2020.04.026.
    1. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369:718–724. doi: 10.1126/science.abc6027.
    1. Zhou Z, Ren L, Zhang L, et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27:883–890.e2. doi: 10.1016/j.chom.2020.04.017.
    1. Li C, Luo F, Liu C, et al. Engineered interferon alpha effectively improves clinical outcomes of COVID-19 patients. 2022. 10.21203/-65224/v1.
    1. Subbarao K. The success of SARS-CoV-2 vaccines and challenges ahead. Cell Host Microbe. 2021;29:1111–1123. doi: 10.1016/j.chom.2021.06.016.
    1. Zheng F, Zhou Y, Zhou Z, et al. SARS-CoV-2 clearance in COVID-19 patients with Novaferon treatment: a randomized, open-label, parallel-group trial. Int J Infect Dis. 2020;99:84–91. doi: 10.1016/j.ijid.2020.07.053.
    1. Rahmani H, Davoudi-Monfared E, Nourian A, et al. Interferon β-1b in treatment of severe COVID-19: a randomized clinical trial. Int Immunopharmacol. 2020;88:106903. doi: 10.1016/j.intimp.2020.106903.
    1. Li C, Luo F, Liu C, et al. Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial. Ann Med. 2021;53:391–401. doi: 10.1080/07853890.2021.1890329.
    1. Khamis F, Al Naabi H, Al Lawati A, et al. Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2021;102:538–543.
    1. Jagannathan P, Andrews JR, Bonilla H, et al. Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun. 2021;12:1967. doi: 10.1038/s41467-021-22177-1.
    1. Hung IF-N, Lung K-C, Tso EY-K, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet Lond Engl. 2020;395:1695–1704. doi: 10.1016/S0140-6736(20)31042-4.
    1. Feld JJ, Kandel C, Biondi MJ, et al. Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir Med. 2021;9:498–510. doi: 10.1016/S2213-2600(20)30566-X.
    1. Davoudi-Monfared E, Rahmani H, Khalili H, et al. A randomized clinical trial of the efficacy and safety of interferon β-1a in treatment of severe COVID-19. Antimicrob Agents Chemother. 2020;64:e01061–e1120. doi: 10.1128/AAC.01061-20.
    1. Monk PD, Marsden RJ, Tear VJ, et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9:196–206. doi: 10.1016/S2213-2600(20)30511-7.
    1. Friedman RM. Clinical uses of interferons. Br J Clin Pharmacol. 2008;65:158–162. doi: 10.1111/j.1365-2125.2007.03055.x.
    1. Davidson S, McCabe TM, Crotta S, et al. IFNλ is a potent anti-influenza therapeutic without the inflammatory side effects of IFNα treatment. EMBO Mol Med. 2016;8:1099–1112. doi: 10.15252/emmm.201606413.
    1. Eiger BioPharmaceuticals. Investigators Brochure. 2018. . accessed 25 Feb 2022.
    1. Bosi E, Bosi C, Rovere Querini P, et al. Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial. Trials. 2020;21:939. doi: 10.1186/s13063-020-04864-4.
    1. Salto-Alejandre S, Palacios-Baena ZR, Arribas JR, et al. Impact of early interferon-β treatment on the prognosis of patients with COVID-19 in the first wave: a post hoc analysis from a multicenter cohort. Biomed Pharmacother. 2022;146:112572. doi: 10.1016/j.biopha.2021.112572.
    1. Pan Y, Zhang D, Yang P, et al. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis. 2020;20:411–412. doi: 10.1016/S1473-3099(20)30113-4.
    1. Fensterl V, Sen GC. Interferons and viral infections. BioFactors Oxf Engl. 2009;35:14–20. doi: 10.1002/biof.6.
    1. Tong A, Baumgart A, Evangelidis N, et al. Core outcome measures for trials in people with Coronavirus Disease 2019: respiratory failure, multiorgan failure, shortness of breath, and recovery. Crit Care Med. 2021;49:503–516. doi: 10.1097/CCM.0000000000004817.
    1. Chauvineau-Grenier A, Bastard P, Servajean A, et al. Autoantibodies neutralizing type I interferons in 20% of COVID-19 deaths in a French Hospital. J Clin Immunol. 2022 doi: 10.1007/s10875-021-01203-3.
    1. Bastard P, Gervais A, Le Voyer T, et al. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 2021;6:eabl4340. doi: 10.1126/sciimmunol.abl4340.
    1. National Institues of Health. Clinical Spectrum of SARS-CoV-2 Infection. COVID-19 Treatment Guidelines. 2021. . Accessed 5 Jan 2022.
    1. Barros FM, Cheinquer H, Tsuchiya CT, et al. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil. Cost Eff Resour Alloc. 2013;11:25. doi: 10.1186/1478-7547-11-25.
    1. Nguyen HA, Cooke GS, Day JN, et al. The direct-medical costs associated with interferon-based treatment for Hepatitis C in Vietnam. Wellcome Open Res. 2020;4:129. doi: 10.12688/wellcomeopenres.15408.2.
    1. Yu Y, Luo D, Chen X, et al. Medication adherence to antiretroviral therapy among newly treated people living with HIV. BMC Public Health. 2018;18:825. doi: 10.1186/s12889-018-5731-z.
    1. Understanding Vaccination Progress by Country. Johns Hopkins Coronavirus Resource Center, . Accessed 21 Feb 2022.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera