Interferon Alfa-2b Research Articles

A selective and sensitive UPLC–ESI-MS/MS method for quantification of Pegylated Interferon Alfa-2b in human serum using signature peptide-based quantitation

A sensitive method for determination of PEG-IFN-α-2b in human serum was developed using ultra performance liquid chromatography aligned with tandem mass spectrometric detection. A two-treatment, two-period, cross over study was conducted to establish bioequivalence between a test and reference formulation and the method was successfully applied to the quantification of PEG-IFN-α-2b in serum samples of this clinical study. The sample concentrations obtained from LC-MS/MS technique were compared with the concentrations obtained from ELISA technique. PEG-IFN-α-2b was isolated from serum using protein precipitation technique with isopropyl alcohol followed by overnight tryptic digestion. The signature peptide formed as result of tryptic digestion was separated on a chromatograph and detected using a mass detector. The mass transition ion-pair of m/z 741.3 → 1047.1 for PEG-IFN-α-2b and m/z 387.4 → 205.2 for internal standard were used for MS/MS detection. The sample extraction involves a simple protein precipitation method followed by tryptic digestion of the supernatant and further sample cleanup was not needed. The method has been validated over a linear range of 1.028–3200 ng/mL with a correlation coefficient ≥ 0.99. The precision (%RSD) was 5.52 to 7.90 and accuracy (%RE) was within −1.80 to 1.68. The total run time was 22.0 min. The sensitivity of LC-MS/MS method was 1.0 ng/ml which was found to be more sensitive than ELISA and resulted in improving the overall study data by being able to quantify all the samples without any below LOQ results helping to further improve the pharmacokinetic modeling. This improved method is a promising anti-body free LC-MS/MS based methodology for estimation of PEG-IFN-α-2b in human serum and may be applied for other such pegylated molecules.

Combined use of interferon alpha-1b, interleukin-2, and thalidomide to reverse the AML1-ETO fusion gene in acute myeloid leukemia

This study aims to explore the effect of the ITI (interferon alpha-1b, thalidomide, and interleukin-2) regimen on the AML1-ETO fusion gene in patients with t(8;21) acute myeloid leukemia (AML) who were in hematologic remission but positive for the AML1-ETO fusion gene. From September 2014 to November 2020; 20 patients with AML (15 from The Affiliated Cancer Hospital of Zhengzhou University, 4 from The First Affiliated Hospital; and College of Clinical Medicine of Henan University of Science and Technology, and 1 from Anyang District Hospital) with hematological remission but AML1-ETO fusion gene positivity were treated with different doses of the ITI regimen to monitor changes in AML1-ETO fusion gene levels. Twenty patients were treated with a routine dose of the ITI regimen, including 13 males and 7 females. The median patient age was 38 (14–70 years). The fusion gene was negative in 10 patients after 1 (0.5 ~ 8.6) month, significantly decreased in 4 patients after 2.8 (1 ~ 6) months, increased in 4 patients, and unchanged in 2 patients. The 4 patients with elevated levels of the fusion gene were treated with an increased dose of the ITI regimen, and all four patients became negative, for a total effective rate of 90%. The ITI regimen reduces AML1-ETO fusion gene levels in patients with AML who are in hematologic remission but are fusion gene–positive. Improvement was observed in patients’ response to a higher dose administration, and patients tolerated the treatment well.

Anti-Lethal Therapy of COVID-19 for Home Health Outpatient Therapy

The article presents the rationale for a new therapeutic strategy for treatment of patients with COVID-19, based on the combined use of biologic response modifiers and drugs targeting etiology and pathophysiology of the novel coronavirus infection, excluding disadvantages of polypharmacy, and providing a high clinical effect. This approach has been predominantly used in home health outpatient treatment of 324 patients with COVID-19 of variable severity using the biologic response modifiers “double drug cocktail” made of recombinant human interleukin-2 and recombinant human interferon alpha-2b in combination with alimemazine, nimesulide, rivaroxaban and antibiotic therapy (co-amoxiclav, or ceftriaxone) if secondary bacterial pneumonia was diagnosed. The results obtained indicate a dramatic improvement in the condition of patients, even with a severe COVID-19, which made possible to avoid artificial ventilation and prevent deaths.

Ocular surface findings in impression cytology after interferon a2b or mitomycin C in rabbits

Objective: To describe ocular surface findings in impression cytology obtained from healthy rabbit conjunctiva treated with interferon alpha-2b eyedrop, and compare them to findings after use of mitomycin C 0.02%. Methods: An experimental study using a rabbit model was performed between September 2013 and October 2014 at the Faculdade de Medicina de Marília, Universidade Federal de São Paulo, Clínica de Olhos Moacir Cunha. Thirty New Zealand white rabbits were divided into 6 groups and received interferon alpha-2b or mitomycin [...]

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Ocular surface squamous neoplasia resistant to topical interferon alpha 2b in a patient with follicular lymphoma

Novel drug for COVID-19: Virafin a therapeutic breakthrough

Background: Pegylated Interferon Alpha-2b is synthesized via the use of PEG (polyethylene glycol). It is formulated via attaching a 12kDa mono methoxy polyethylene glycol moiety to the recombinant human Interferon Alpha-2b protein. Pegylated Interferon Alpha-2b acts via binding to the (JAK/STAT) Janus kinase signal transducer and activator of the transcription interferon receptor. The Pegylated Interferon Alpha-2b /Virafin binds to the (IFNAR1/2) alpha interferon receptor 1 and 2. Pegylated Interferon Alpha-2b better known as Virafin has been approved by the Drugs Controller General of India. This therapeutic agent is currently under a multicentric phase 3 trial with very promising results being reported. A single subcutaneous dose of Virafin has been shown to decrease the need for oxygen therapy in patients. This reduction in the need for oxygen therapy is a vital factor needed to provide relief to the Indian medical system in light of the recent oxygen shortages faced due to India’s worst wave of COVID-19 cases since the onset of the global pandemic. Pegylated Interferon Alpha-2b/ Virafin confers enhanced viral clearance and bolsters the immune response to induce a quicker recovery in patients with mild to moderate symptoms.
 Conclusion: It is of paramount importance that further research on Virafin is undertaken as it can hinder the progression of COVID-19, reduce pressure on the inundated health systems, and save countless lives.

Complex analysis of the personalized pharmacotherapy in the management of COVID-19 patients and suggestions for applications of predictive, preventive, and personalized medicine attitude

AimsCoronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Drug therapy is one of the major treatments, but contradictory results of clinical trials have been reported among different individuals. Furthermore, comprehensive analysis of personalized pharmacotherapy is still lacking. In this study, analyses were performed on 47 well-characterized COVID-19 drugs used in the personalized treatment of COVID-19.MethodsClinical trials with published results of drugs use for COVID-19 treatment were collected to evaluate drug efficacy. Drug-to-Drug Interactions (DDIs) were summarized and classified. Functional variations in actionable pharmacogenes were collected and systematically analysed. “Gene Score” and “Drug Score” were defined and calculated to systematically analyse ethnicity-based genetic differences, which are important for the safer use of COVID-19 drugs.ResultsOur results indicated that four antiviral agents (ritonavir, darunavir, daclatasvir and sofosbuvir) and three immune regulators (budesonide, colchicine and prednisone) as well as heparin and enalapril could generate the highest number of DDIs with common concomitantly utilized drugs. Eight drugs (ritonavir, daclatasvir, sofosbuvir, ribavirin, interferon alpha-2b, chloroquine, hydroxychloroquine (HCQ) and ceftriaxone had actionable pharmacogenomics (PGx) biomarkers among all ethnic groups. Fourteen drugs (ritonavir, daclatasvir, prednisone, dexamethasone, ribavirin, HCQ, ceftriaxone, zinc, interferon beta-1a, remdesivir, levofloxacin, lopinavir, human immunoglobulin G and losartan) showed significantly different pharmacogenomic characteristics in relation to the ethnic origin of the patient.ConclusionWe recommend that particularly for patients with comorbidities to avoid serious DDIs, the predictive, preventive, and personalized medicine (PPPM, 3 PM) strategies have to be applied for COVID-19 treatment, and genetic tests should be performed for drugs with actionable pharmacogenes, especially in some ethnic groups with a higher frequency of functional variations, as our analysis showed. We also suggest that drugs associated with higher ethnic genetic differences should be given priority in future pharmacogenetic studies for COVID-19 management. To facilitate translation of our results into clinical practice, an approach conform with PPPM/3 PM principles was suggested. In summary, the proposed PPPM/3 PM attitude should be obligatory considered for the overall COVID-19 management.

Antiviral drugs arbidol and interferon alpha-1b contribute to reducing the severity of COVID-19 patients: a retrospective cohort study

ObjectivesThe aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia.MethodsThis retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People’s Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir–ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness.ResultsOf the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084–0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15–0.58, p = 0.0005). The use of lopinavir–itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of − 5.2 days (IQR − 3.0 to − 7.5, p = 4e−06) compared with the control group.ConclusionTreatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients’ recovery time.

Recombinant Interferon Alpha-2b as Primary Treatment for Ocular Surface Squamous Neoplasia.

Purpose:To investigate the effects of topical and perilesional interferon alpha-2b as primary treatment for ocular surface squamous neoplasia (OSSN).Methods:In this prospective interventional case series, topical interferon alpha-2b (3 MIU/mL) was used as the initial treatment of OSSN, with perilesional interferon alpha-2b (3 MIU/mL) added based on clinical response. The primary outcome was complete tumor resolution. Spearman's rank correlation test was used to investigate the association of complete tumor resolution and time to resolution with baseline tumor characteristics and the American Joint Committee on Cancer (AJCC) classification for OSSN.Results:Ninety-two patients (92 OSSN tumors) were included in the study. The total follow-up duration was 13.57 ± 2.14 months (median: 12, range: 3–23). The median basal tumor diameter was 4 mm (mean: 4.13 ± 1.37). Complete tumor resolution was achieved in 89 cases (96.73%), with a median time to complete tumor resolution of 5 months (mean: 4.64 ± 1.92). Complete tumor resolution was 57 of 57 in T1 (100%), 8 of 9 in T2 (88.88%), and 21 of 23 in T3 (91.30%). There were statistically significant correlations between AJCC classification and complete tumor resolution (Spearman's r = −0.22, P = 0.03) and maximal basal tumor diameter and the time to complete resolution (Spearman's r = 0.35, P = 0.001). There were no recurrences during the study follow-up period.Conclusion:Topical interferon alpha-2b is effective and well tolerated as a primary treatment for OSSN, with a high rate of tumors responding completely to therapy.

Is Interferon α-2b 1 MillionIU/mL Truly Better Than Tacrolimus 0.03% for Steroid-Resistant VKC ?: Our 2-Year Experience at a Tertiary Health-Care Centre.

PurposeTo compare the efficacy of eye-drop interferon (IFN) α-2b 1 millionIU/mL with eye-ointment tacrolimus 0.03% in refractory vernal keratoconjunctivitis (VKC).Materials and MethodsFifty patients with VKC refractory to conventional treatment with topical corticosteroids and antihistamines after 4 weeks of regular use were selected retrospectively. Patients were divided into two groups depending on whether they received eye-ointment tacrolimus 0.03% three times a day or eye-drop IFN alpha-2b 1 millionIU/mL three times a day and were followed up for 24 months. The main outcome measures were total subjective symptom score (TSSS) and total objective ocular score (TOSS).ResultsMean baseline TSSS was 7.24±1.98 in Group A (tacrolimus group) and 7.84±1.82 in Group B (IFN group), and it reduced to 1.12±0.83 in Group A and 0.62±0.41 in Group B at 6 months, which was statistically significant compared to the baseline score (p<0.05) as well as between the two groups. Mean baseline TOSS was 6.72±2.07 in Group A and 6.56±2.04 in Group B, and it improved to 1 month onwards to 1.52±0.87 in Group A and 1.0±0.71 in Group B at 6 months, which was statistically significant compared to the baseline score (p<0.05) as well as between the two groups. Side effects like stinging and burning sensations were seen in the tacrolimus group only.ConclusionOur study suggests that while both eye-drop IFN α-2b 1 millionIU/mL and eye-ointment tacrolimus eye ointment 0.03% are both safe and effective steroid-sparing agents in steroid-resistant VKC. IFN α-2b results in greater improvement in subjective symptoms and objective signs, has fewer side effects in long term and is better tolerated as compared to tacrolimus.

Unusual Long Term Remission in Multiple Myeloma Using Conventional Therapy Combined with Danazol

Introduction and Case studies. The treatment of multiple myeloma (MM) has drastically changed over the past decade with significantly improved progression free as well as overall survival. Despite the advent of multiple treatment options, MM still has the inherent ability to become resistant. Relapses are frequent and the disease becomes refractory to treatment, leading to significant morbidity and mortality. Long term remissions lasting over a decade without relapses are rare in MM with conventional treatment.We report here prolonged remission lasting for decades in two patients with MM who were treated with conventional alkylating agents and steroids, combined with danazol as adjuvant and maintenance therapy. Both achieved complete remissions with undetectable M proteins and remarkable clinical improvement and better quality of life. The remissions were maintained now over two decades.Our first case was a 51 year old man who presented with severe back pain and noticeable loss of height. Work up revealed many lytic lesions and multiple collapsed vertebrae with diffuse osteoporosis on skeletal bone survey. Hematologic studies revealed high levels of IgG-lambda M protein of 6 grams. He was treated with melphalan, prednisone, monthly Aredia and danazol 200 mg three times daily (TID). He achieved a complete remission (CR) with marked clinical improvement. His remission was maintained with danazol 200 mg TID and Intron-A (interferon alfa-2b, recombinant) 5 million units three times a week. Danazol was later reduced to three times a week in combination with interferon, doses of which he remains on today. He remains in CR now for over 21 years without signs of relapse. He resumed all of his normal activities and is currently working without any limitation as a full time college professor. He refuses to stop danazol nor Intron-A.Our second case was a 41 year old man with 3 year history of progressive polyneuropathy that rendered him severely paraplegic, bedridden and unable to feed himself because of weakness. Work up revealed an IgG lambda M protein and multiple sclerotic bone lesions on bone survey. Excisional bone biopsy showed neoplastic plasma cell proliferation. Diagnosis of osteosclerotic multiple myeloma with POEMS syndrome was made. He was treated initially with plasmapheresis and infusions of IVIG without any long tern benefit. Subsequently, he received palliative radiation therapy to relieve bone pain and was treated with chlorambucil 3 mg PO daily, hydrocortisone 20 mg PO daily, danazol 200 mg PO TID and monthly Aredia which was later changed to Zometa. He achieved a CR with remarkable clinical recovery. His strength improved significantly with the ability to walk and feed himself as well as resumption of his normal daily activities (Muscle Nerve. 1997, 8:1035). He stopped danazol and remains in remission now over 22 years.Conclusion/Discussion: The use of immunomodulators (IMiDs) have changed the approach to the treatment of MM. While the mechanism of action is not fully understood, IMiDs appear to possess anti-myeloma properties including immunomodulation, anti-angiogenesis, and anti-proliferative activities (Leukemia. 2010, 24:22).Danazol, an attenuated androgen, is widely used in the treatment of ITP (NEJM. 1983, 308:1396). We previously showed that danazol carries inherent immunomodulatory action, increasing T-helper cells as well as the proportion of T-helper to T-suppressor cells among patients treated for ITP (Clin Imm Immunopath. 1987, 42:287). Administration of danazol in patients for ITP for over a year, even with withdrawal, yielded long term remissions while relapses were more frequent in those that took it for less than 6 months (Ann Intern Med. 1989, 111:723). Similar observation was made in other autoimmune disease such as immune hemolytic anemia (Acta Hematol. 1990, 84:122). Collectively, long term administration of danazol appears to induce prolonged unmaintained remission in autoimmune diseases like ITP. We postulate that danazol may induce similar immunomodulation in MM and contributed to decades of remission in our patients. Danazol has not yet been tested in the treatment of MM systematically but deserves further investigation through a large prospective clinical trial. DisclosuresNo relevant conflicts of interest to declare.

Nilotinib in Combination with Pegylated Interferon Alfa-2b for CP-CML Leads to High Molecular Response Rates: Interim Results of the Pinnacle Study

Nilotinib in Combination with Pegylated Interferon Alfa-2b for CP-CML Leads to High Molecular Response Rates: Interim Results of the Pinnacle Study

Comparative Analysis of Adverse Drug Reactions between Interferon Alpha 2B and Sofosbuvir in the Treatment of Hepatits C at GIMHS, Sindh, Pakistan

A descriptive cross-sectional study was conducted on 300 patients selected by random sampling who were reported with Hepatitis-C at GIMHS. Questions were asked from patients regarding symptoms and adverse drug reactions (ADR’S). Results were analyzed by using SPSS-22. Out of total patients (n=300) the frequency of male gender was (n=192) as compared to females (n=108). Among 300 patients some patients were on sofosbuvir (n=150), patients on interferon (n=150). Rate of ADR’S observed with interferon as fever (n=28), anemia (n=27), hair loss (n=21), headache (n=19), insomnia (n= 11), nausea (n=13), depression (n=14, 09), malaise (n=25), vomiting (n=06), ulcer (n=13), pain and redness at site of injection (n=17). While rate of ADR’S in patients who were on sofosbuvir, fever (n=33), chill (n=17), nausea (n=28), anemia (n=06), headache (n=14), insomnia (n=13), loss of appetite (n=5), diarrhea (n=1). This study concluded that as compared to Interferon, rate of ADR’S were less with Sofosbuvir.

Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma.

9501 Background: We assessed whether or not adjuvant pembrolizumab given over 1 year would improve OS and RFS in comparison to high dose ipilimumab (ipi10) or HDI - the two FDA-approved adjuvant treatments for high risk resected melanoma at the time of study design. Methods: Patients age 18 or greater with resected stages IIIA(N2), B, C and IV were eligible. Patients with CNS metastasis were excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel node positive disease. Prior therapy with PD-1 blockade, ipilimumab or interferon was not allowed. Two treatment arms were assigned based on stratification by stage, PD-L1 status (positive vs. negative vs. unknown), and intended control arm (HDI vs. Ipi10). Patients enrolled between 10/2015 and 8/2017 were randomized 1:1 to either the control arm [(1) interferon alfa-2b 20 MU/m2 IV days 1-5, weeks 1-4, followed by 10 MU/m2/d SC days 1, 3, and 5, weeks 5-52 (n=190), or (2) ipilimumab 10 mg/kg IV q3w for 4 doses, then q12w for up to 3 years (n=465)], or the experimental arm [pembrolizumab 200 mg IV q3w for 52 weeks (n=648)]. The study had three primary comparisons: 1) RFS among all patients, 2) OS among all patients, 3) OS among patients with PD-L1+ baseline biopsies. Results: 1,426 patients were screened and 1,345 patients were randomized with 11%, 49%, 34%, and 6% AJCC7 stage IIIA(N2), IIIB, IIIC and IV, respectively. This final analysis was performed per-protocol 3.5 years from the date the last patient was randomized, with 512 RFS and 199 OS events. The pembrolizumab group had a statistically significant improvement in RFS compared to the control group (pooled HDI and ipi10) with HR 0.740 (99.618% CI, 0.571 to 0.958). There was no statistically signifcant improvement in OS in the 1,303 eligible randomized overall patient population with HR 0.837 (96.3% CI, 0.622 to 1.297), or among the 1,070 (82%) patients with PD-L1 positive baseline biopsies with HR 0.883 (97.8% CI, 0.604 to 1.291). Gr 3/4/5 event rates were as follows: HDI 69/9/0%, ipi10 43/5/0.5% and pembrolizumab 17/2/0.3%. Conclusions: Pembrolizumab improves RFS but not OS compared to HDI or ipi10 in the adjuvant treatment of patients with high-risk resected melanoma. Pembrolizumab is a better tolerated adjuvant treatment regimen than HDI or Ipi10. Support: NIH/NCI NCTN grants CA180888, CA180819, CA180820, CA180863; and in part by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA. Editorial Acknowledgement: With special thanks to Elad Sharon, MD, MPH, and Larissa Korde, MD, MPH. National Cancer Institute, Investigational Drug Branch, for their contributions to this trial, as well as Nageatte Ibrahim, MD, and Sama Ahsan, MD Merck. Clinical trial information: NCT02506153.

In vitro activity of human recombinant alpha-2b interferon against SARS-CoV-2 virus

The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (&gt;1000). Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

Intrapleural Steroid Instillation for Critically Ill Patients With Covid-19 Severe Adult Respiratory Distress Syndrome.

Within a very short period, outbreaks of a novel coronavirus disease (COVID-19) have affected 183 countries worldwide. COVID-19 resolves acutely, but it has resulted in thousands of deaths, with an overall fatality rate of 2% to 5% (1). Among the fatal cases, over 50% of patients died from respiratory failure with massive alveolar damage due to virus-activated “cytokine storm syndrome” (2). Of these patients, 67% developed adult respiratory distress syndrome (ARDS), 29% developed acute kidney injury, 23% developed cardiac injury, and 29% experienced liver dysfunction (3). The intensive care unit (ICU) mortality rate among those who required invasive mechanical ventilation was 86% (4), and the mortality of patients who received extracorporeal membrane oxygenation was also extremely high (5). Until now, there have been no proven effective specific treatment strategies and so methylprednisolone may be the best option for COVID-19 patients who develop ARDS (6). Although interferon alfa-2b, antiviral therapy, antibiotics for the prevention of secondary infection, and methylprednisolone were all administered to attenuate lung inflammation, histological examination still revealed bilateral diffuse alveolar damage with hyaline membrane formation in an autopsy of a patient (7). According to the imaging changes and pathological findings associated with ARDS, a tubular and enlarged appearance of the pulmonary vessels with a sudden caliber reduction seen within ground glass opacity lesions showing partial consolidation and fibrosis should be expected in severe cases of COVID-19 (8, 9). Fortunately, corticosteroids have a greater anti-inflammatory effect when administered intrapleurally, rather than via the intravenous route, because the permeability of the damaged visceral pleural membrane increases during pulmonary edema and steroid treatment, with the characteristic of fat-solubility, further permits infiltration into the lung parenchyma. Glucocorticoids can easily pass through the visceral pleura and bind to steroid hormone receptors, thereby allowing them to reach the injured areas and avoiding the problems of a ventilation–perfusion mismatch and the need for a shunt via intratracheal instillation or intravenous instillation. Glucocorticoids can normalize the ion pump (Na-K pump) and increase the synthesis of Na+/K+-ATPase, thus contributing to reductions in lung edema and optimization of oxygenation because alveolar fluid clearance is impaired in the majority of patients with ARDS (10). In COVID-19 severe refractory ARDS, more aggressive management is required to reduce the inflammatory reaction and consequent lung injury. The results of our study provide more evidence supporting the efficacy of intrapleural steroid instillation (IPSI) in the treatment of ARDS with multiple organ failure (11). This alternative treatment resulted in significant improvement in oxygenation and survival benefits after 5 days of treatment. The dosing schedule of intrapleural methylprednisolone was initially 40 mg q6 h in both pleural cavities, but the dose was reduced on the basis of chest radiography appearance, inspired oxygen concentration demand, and positive end-expiratory pressure of the ventilator. Thoracic catheterization was easily performed because COVID-19 patients usually had significant pleural effusion. Although managing COVID-19 pneumonia is currently a major issue for ICU healthcare providers around the world, IPSI will greatly improve the ability to respond effectively to current needs. Our recommendation in this severe case of COVID-19 might help physicians implement suitable therapeutic strategies for similar severe patients and reduce mortality.

Ulcerative colitis triggered by pegylated interferon alpha-2b in a patient with chronic hepatitis B: A case report and literature review

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

The use in pediatrics of recombinant interferon alfa-2b preparations in the dosage form rectal suppositories: whom? when? which ones?

The paper presents the indications and main differences of frequently used rectal suppositories containing interferon alpha-2b.The features and differences in the contained excipients are highlighted. A range of diseases in children's practice is presented, in which candles are shown VIFERON®, Kipferon®, Genferon light®

The value of interferon therapy for COVID-19 in children

The article presents a literature review, which provides data on the role of interferons in the immunopathogenesis of COVID-19 and the clinical efficacy of drugs based on recombinant interferon-alpha 2b in the treatment of children with new coronavirus infection. Shown the leading role ofinterferons as factors of the first line of defense against various viruses, including SARS-CoV-2. Numerous studies have proven the feasibility of including interferon preparations in COVID-19 therapyregimens in children, both as combinations with antiviral agents and as monotherapy.

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

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.