A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization

Chen, Lina; Shi, Mingfang; Deng, Quanmin; Liu, Wenjun; Li, Qin; Ye, Piao; Xiao, Yu; Zhang, Benjin; Xu, Yan; Li, Xiaolan; Yang, Yao-Lun; Li, Min; Yan, Yi; Xu, Zhe; Yu, Jihong; Xiang, Long; Tang, Xiaojun; Wan, Guangping; Cai, Qiang; Wang, Li; Bo, Hu; Xie, Liang; Li, Gen; Xie, Lunyan; Liu, Xiaoyun; Liu, Chunyan; Li, Li; Chen, Lijie; Jiang, Xiaobin; Huang, Yana; Wang, Si; Guo, Jiang; Shi, Yan; Wang, Xiaofang; Zhao, Zhiyong; Li, Yan; Liu, Yanru; Fu, Qiang; Zeng, Yan; Zou, Yan; Liu, Dingyuan; Wan, Deyun; Ai, Tao; Liu, Hanmin

doi:10.1371/journal.pone.0228391

Cited by 16 publications

(16 citation statements)

References 8 publications

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“…For interferon atmotherapy, patients received 5 × 10 6 units of interferon α-2b (INFα-2b) nebulized in 4 ml of 0.9% saline with the following parameter: an air-flow rate of 3.0–6.0 L/min, pressure of 90 k−120 kPa, an atomization rate of 350 ± 50 mg/min, and an equivalent volume particle size distribution of MMD: 4.2 ± 25%. Therapy was once daily over 20 min ( 14 , 15 ) using a compression atomizer (model: BRM-075II).…”

Section: Methodsmentioning

confidence: 99%

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

et al. 2021

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Background: Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19.Methods: In this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Jul. 08, 2020. Clinical, demographic, and laboratory data were collected. Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS-CoV-2 with regard to metabolism pathways.Results: A total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors for mortality were elevated D-Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p = 0.005), high immune-related metabolic index (6.42 [95% CI 2.66–15.48], p < 0.001), and increased neutrophil-to-lymphocyte ratio (1.08 [95% 1.03–1.13], p < 0.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI 0.17–0.51], p < 0.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56–75.72], p < 0.001), fatty acid (15.61 [95% CI 6.66–36.6], p < 0.001), and pyruvate (12.86 [95% CI 5.85–28.28], p < 0.001) showed a consistently lower flux in the survivors vs. the deceased subgroup. This may reflect a key pathogenic mechanism of COVID-19 infection.Conclusion: Several factors such as interferon atmotherapy and recreased activity of specific metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, a survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Dysregulation of the metabolic pathways revealed in this study may aid in the drug and vaccine development against COVID-19.

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Section: Methodsmentioning

confidence: 99%

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

et al. 2021

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“…A multicenter, randomized, prospective study on pediatric patients with respiratory syncytial virus investigated the use of nebulized INFα-1b compared with the subcutaneous injection. The study revealed that the nebulized form has a faster onset of action, a direct action on the mucosal epithelial cells in the lungs, less systemic adverse effects, and is less invasive to the pediatric population compared with the subcutaneous form [105].…”

Section: Interferonsmentioning

confidence: 98%

Pharmaco-Immunomodulatory Therapy in COVID-19

Rizk

Kalantar-Zadeh

Mehra

et al. 2020

Drugs

248

244

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The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colonystimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms. Key Points COVID-19 is a syndrome of viral replication and a host inflammatory response. Tackling the immune response may be as important as addressing viral replication. Specific and non-specific immune modulators have the potential to inhibit cytokines and quell the cytokine storm.

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“…A similar study performed in RSV-positive infants observed no difference in either clinical signs or viral shedding between the IFNα2a treatment group and placebo controls [ 93 ]. In contrast, a recent study observed that nebulized IFN-α1b administered to children immediately following the onset of bronchiolitis symptoms reduced wheezing and coughing compared to controls receiving only minimal analgesics and antipyretics [ 94 ]. This suggests that the administration route and the class of type I IFN used may differentially affect RSV disease in humans.…”

Section: Use Of Type I Ifns In Therapeutic and Preventative Stratementioning

confidence: 99%

Function and Modulation of Type I Interferons during Respiratory Syncytial Virus Infection

Stephens

Varga

2020

Vaccines

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory infections in infants and young children, accounting for an estimated 3 million hospitalizations annually worldwide. Despite the major health burden, there is currently no licensed RSV vaccine. RSV is recognized by a range of cellular receptors including both toll-like receptors (TLR) and retinoic acid-inducible gene-I-like receptors (RIG-I). This interaction initiates signaling through mitochondrial antiviral signaling (MAVS) and interferon regulatory factor (IRF) proteins, resulting in the induction of type I interferons (IFN). Early viral control is mediated by either IFN-α or IFN-β signaling through the IFN receptor (IFNAR), inducing the production of antiviral interferon-stimulating genes (ISGs). Type I IFNs also initiate the early production of proinflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor (TNF), and IFN-γ. Type I IFN levels correlate with age, and inadequate production may be a critical factor in facilitating the increased RSV disease severity observed in infants. Here, we review the current literature on the function of type I IFNs in RSV pathogenesis, as well as their involvement in the differential immune responses observed in infants and adults.

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A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization

Cited by 16 publications

References 8 publications

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

Pharmaco-Immunomodulatory Therapy in COVID-19

Function and Modulation of Type I Interferons during Respiratory Syncytial Virus Infection

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