Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study

Hao, Shao rui; Ren, Yan; Zhang, Shan yan; Lian, Jiang; Cai, Huan; Zhang, Xiao li; Zheng, Lin; Hong, Jie; Hu, Jian; Yu, Guo; Gu, Jue; Ye, Chan yuan; Jin, Ci liang; Lü, Ying; Xin, Jiao jiao; Sheng, Ji fang; Yang, Yi

doi:10.1631/jzus.b2000211

Cited by 14 publications

(8 citation statements)

References 29 publications

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“…Such an approach was taken in a recent analysis of an uncontrolled exploratory study of nebulised interferon alfa-2b, reported in a hospital setting in Wuhan, China, indicating a positive effect on viral load and the inflammatory biomarkers interleukin-6 and C-reactive protein, although there was an imbalance in age between treated patients and controls. 28 , 29 More recently, a similar, pragmatic, open-label study reported clinical benefits with aerosol inhalation of interferon kappa plus trefoil factor 2, showing reductions in viral shedding and duration of symptoms and hospital stay in patients with SARS-CoV-2 infection. 30 Taken together with our study, these results suggest a potential antiviral benefit of aerosolised interferon therapy in COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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

Monk

Marsden

Tear

et al. 2021

The Lancet Respiratory Medicine

410

354

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. Methods We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov ( NCT04385095 ); the pilot trial of inpatients with COVID-19 is now completed. Findings Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 [95% CI 1·07–5·04]; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 [95% CI 1·03–4·69]; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven [15%] patients in the SNG001 group and five [10%] in the placebo group). There were three deaths in the placebo group and none in the SNG001 group. Interpretation Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials. Funding Synairgen Research.

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Section: Discussionmentioning

confidence: 99%

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

Monk

Marsden

Tear

et al. 2021

The Lancet Respiratory Medicine

410

354

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“… [175] , [176] A case-control study presented varying results on the effects of IFNα inhalation in reducing viral shedding time and the length of hospitalization. [52] Patients treated with IFN-α2b inhalation had significantly shorter viral shedding time and hospitalization; however, statistical significance was lost after applying the propensity score matching method. Treatment was initiated for the IFNα group (which consisted of 41 mild, 22 severe, and 5 critically ill patients) at a median of 5 days (Q1-Q3: 3-8), and no difference in the timing of treatment initiation was found when compared with the control group.…”

Section: Comprehensive Review Of the Literature On The Safety And Efficacy Of Interferon Alpha Treatment In Covid-19 Patientsmentioning

confidence: 97%

“…A total of 178 studies were found to have reported IFNα treatment for COVID-19 (Supplemental 2). [13] , [17] , [19] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , …”

Section: Comprehensive Review Of the Literature On The Safety And Efficacy Of Interferon Alpha Treatment In Covid-19 Patientsunclassified

“…To illustrate the issue in statistical analysis, we described here a case-control study [52] that compared outcomes between patients treated with and without IFNα inhalation, in which matched and unmatched datasets were used for multivariate cox regression analysis. In unmatched analysis, IFNα inhalation was associated with reduced ICU admission, viral shedding time, and length of hospitalization as well as increased discharge rate, whereas in matched analysis, no associations were found.…”

Section: Further Considerations Of This Reviewmentioning

confidence: 99%

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Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

Lu¹,

Feng²,

Yu³

et al. 2022

Cytokine & Growth Factor Reviews

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Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1 st , 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.

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“…Another study using IFN-α2b via spray inhalation to 68 patients matched with 36 case controls, with both groups with PCR confirmed COVID-19, did not demonstrate reduced viral shedding but signaled shorter hospitalization times ( 83 ).…”

Section: Intranasal Interferons In Prevention and Treatment Of Viral ...mentioning

confidence: 99%

Review: The Nose as a Route for Therapy. Part 2 Immunotherapy

et al. 2021

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The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant “reservoir” for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.

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Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study

Cited by 14 publications

References 29 publications

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

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

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

Review: The Nose as a Route for Therapy. Part 2 Immunotherapy

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