Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
Medicina (Kaunas) ; 58(4)2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1810017

ABSTRACT

Background and Objectives: Providing a proper quality control of drugs is essential for efficient treatment of various diseases minimizing the possible side effects of pharmaceutical active substances and potential impurities. Recent in vitro and in vivo studies have shown that certain heavy metalloids and metals interfere with protein folding of nascent proteins in cells and their biological function can be altered. It is unknown whether the drug impurities including heavy metals may affect the tertiary protein structure. Materials and Methods: ReciGen and Rebif are pharmaceutical interferon beta-1a (IFNß-1a) contained in preparations that are used for parenteral administration. Heavy metal impurities of these samples have been studied by gel electrophoresis, Fourier-transform infrared spectroscopy (FTIR) and inductively coupled plasma mass spectrometry analysis (ICP MS). The concentration of heavy metals including mercury, arsenic, nickel, chromium, iron, and aluminum did not exceed permitted levels established by International Council for Harmonisation guideline for elemental impurities. Results: The ICP MS analysis revealed the presence of heavy metals, moreover zeta potential was significantly different for IFNß-1a, which can be an indirect indication of the difference in composition of ReciGen and Rebif samples, respectively. FTIR analysis revealed very similar amide I and II bonds at 1654 and 1560 cm-1 attributed to the peptide absorption peaks of IFNß-1a in Rebif and ReciGen. Conclusions: It was hypothesized that the IFNß-1a complex binds heavy metals affecting the tertiary protein structure and may lead to some side effects of drug administration. Further testing of IFNß-1a bioequivalence for parenteral application is necessary.


Subject(s)
Interferon-beta , Metals, Heavy , Humans , Interferon beta-1a , Interferon-beta/therapeutic use , Ions , Metals, Heavy/toxicity , Pharmaceutical Preparations
2.
Neurol Neuroimmunol Neuroinflamm ; 9(2)2022 03.
Article in English | MEDLINE | ID: covidwho-1643219

ABSTRACT

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/epidemiology , Adult , Age Factors , Case-Control Studies , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Interferon-beta/therapeutic use , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/therapeutic use , Odds Ratio , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Time Factors
3.
Clin Drug Investig ; 41(12): 1037-1046, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1540301

ABSTRACT

BACKGROUND AND OBJECTIVE: Interferon-ß, as with several other anti-viral agents, has been investigated as a treatment option for COVID-19 as a repurposed drug. The present study is a systematic review and meta-analysis of interferon-ß to determine its efficacy among moderate-to-severe COVID-19 patients. METHODS: A systematic literature search was done using relevant terms for 'COVID-19' and 'interferon-ß'. Randomised controlled trials (RCT) evaluating the efficacy of interferon-ß in COVID-19 were included. Data were extracted for outcome measures, namely mortality, time to clinical improvement and length of hospital stay. Random effects meta-analysis was performed using RevMan V.5.4.1 to calculate overall effect estimate as odds ratio/hazard ratio for categorical variables and mean difference for continuous variable. RESULT: Eight RCTs were eligible for qualitative synthesis and seven for meta-analysis. The overall effect estimate (odds ratio [OR] 0.59; 95 % CI 0.91, 1.12) and (mean difference [MD] - 1.41; 95 % CI - 2.84, 0.02) indicated no statistically significant difference between effect of IFN-ß and that of control on mortality and length of hospital stay, respectively. However, the overall effect estimate (hazard ratio [HR] 1.95; 95 % CI 1.36, 2.79) denoted a favourable effect of INF-ß on reducing the time to clinical improvement in moderate-to-severe COVID-19 patients. CONCLUSION: Addition of interferon-ß to standard of care resulted in significant reduction in time to clinical improvement but no significant benefit in terms of reduction in mortality and length of hospital stay in moderate-to-severe cases of COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , Humans , Interferon-beta/therapeutic use , SARS-CoV-2
4.
BMC Infect Dis ; 21(1): 814, 2021 Aug 13.
Article in English | MEDLINE | ID: covidwho-1477274

ABSTRACT

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Interferon-beta/therapeutic use , Randomized Controlled Trials as Topic , COVID-19/diagnosis , COVID-19/transmission , COVID-19 Testing , Humans , SARS-CoV-2 , Treatment Outcome
5.
Acta Med Acad ; 49(2): 130-143, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1414828

ABSTRACT

In this review, we discuss the latest developments in research pertaining to virus-induced asthma exacerbations and consider recent advances in treatment options. Asthma is a chronic disease of the airways that continues to impose a substantial clinical burden worldwide. Asthma exacerbations, characterised by an acute deterioration in respiratory symptoms and airflow obstruction, are associated with significant morbidity and mortality. These episodes are most commonly triggered by respiratory virus infections. The mechanisms underlying the pathogenesis of virus-induced exacerbations have been the focus of extensive biomedical research. Developing a robust understanding of the interplay between respiratory viruses and the host immune response will be critical for developing more efficacious, targeted therapies for exacerbations. CONCLUSION: There has been significant recent progress in our understanding of the mechanisms underlying virus-induced airway inflammation in asthma and these advances will underpin the development of future clinical therapies.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antiviral Agents/therapeutic use , Asthma/drug therapy , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Adenovirus Infections, Human/drug therapy , Adenovirus Infections, Human/immunology , Adenovirus Infections, Human/physiopathology , Administration, Inhalation , Asthma/immunology , Asthma/physiopathology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Disease Progression , Humans , Influenza, Human/drug therapy , Influenza, Human/immunology , Influenza, Human/physiopathology , Interferon-beta/therapeutic use , Macrolides/therapeutic use , Omalizumab/therapeutic use , Paramyxoviridae Infections/drug therapy , Paramyxoviridae Infections/immunology , Paramyxoviridae Infections/physiopathology , Picornaviridae Infections/drug therapy , Picornaviridae Infections/immunology , Picornaviridae Infections/physiopathology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/physiopathology , Virus Diseases/immunology , Virus Diseases/physiopathology
6.
Trials ; 22(1): 584, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1388817

ABSTRACT

OBJECTIVES: The primary objective of the study is to demonstrate the efficacy of low-dose IFN-ß in reducing the risk of SARS-CoV-2 recently infected elderly patients to progress towards severe COVID-19 versus control group within 28 days. Secondary objectives are: 1) To assess the reduction in Intensive Care Unit (ICU) admission in patients treated with IFN-ß versus control group within 28 days of randomization 2) To assess the reduction in number of deaths in IFN- ß compared to control group (day 28) 3) To evaluate the increase in proportion of participants returning to negative SARS-CoV-2 RT-PCR in IFN-ß -treated versus control group at Day 14 and Day 28 4) To assess the increase in SARS-CoV-2-specific binding antibody titers in IFN-ß compared to control group (day 28) 5) To assess the safety of IFN-ß -treated patients versus control group TRIAL DESIGN: Randomized, Open-Label, Controlled, Superiority Phase II Study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the two treatment groups in a ratio 2:1 (IFN-treated versus control patients). Randomization will be stratified by gender. Stratified randomization will balance the presence of male and female in both study arms. PARTICIPANTS: Male and female adults aged 65 years or older with newly diagnosed SARS-CoV-2 infection and mild COVID-19 symptoms are eligible for the study. The trial is being conducted in Rome. Participants will be either hospitalized or home isolated. A group of physicians belonging to the Special Unit for Regional Continued Care (USCAR), specifically trained for the study and under the supervision of the National Institute for Infectious Diseases "Lazzaro Spallanzani", will be responsible for the screening, enrolment, treatment and clinical monitoring of patients, thus acting as a bridge between clinical centers and territorial health management. Inclusion criteria are as follows: ≥ 65 years of age at time of enrolment; Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, in any specimen < 72 hours prior to randomization; Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures; Understands and agrees to comply with planned study procedures; Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol; Being symptomatic for less than 7 days before starting therapy; NEWS2 score ≤2. Exclusion criteria are as follows: Hospitalized patients with illness of any duration, and at least one of the following: Clinical assessment (evidence of rales/crackles on exam) and SpO2 ≤ 94% on room air at rest or after walking test, OR Acute respiratory failure requiring mechanical ventilation and/or supplemental oxygen; Patients currently using IFN-ß (e.g., multiple sclerosis patients); Patients undergoing chemotherapy or other immunosuppressive treatments; Patients with chronic kidney diseases; Known allergy or hypersensitivity to IFN (including asthma); Any autoimmune disease (resulting from patient anamnesis); Patients with signs of dementia or neurocognitive disorders; Patients with current severe depression and/or suicidal ideations; Being concurrently involved in another clinical trial; HIV infection (based on the anamnesis); Use of any antiretroviral medication; Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min); Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition); Any physical or psychological impediment in a patient that could let the investigator to suspect his/her poor compliance; Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: Control arm: No specific antiviral treatment besides standard of care. Treatment arm: 11µg (3MIU) of IFN-ß1a will be injected subcutaneously at day 1, 3, 7, and 10 in addition to standard of care. The drug solution, contained in a pre-filled cartridge, will be injected by means of the RebiSmart® electronic injection device. Interferon ß1a (Rebif®, Merck KGaA, Darmstadt, Germany) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS). The dose selected for this study is expected to exploit the antiviral and immunomodulatory properties of the cytokine without causing relevant toxicity or inducing refractoriness phenomena sometimes observed after high-dose and/or chronic IFNß treatments. MAIN OUTCOMES: Primary endpoint of the study is the proportion of patients experiencing a disease progression, during at least 5 days, according to the National Early Warning Score (NEWS2). The NEWS2 score is a standardized approach aimed at promptly detecting signs of clinical deterioration in acutely ill patients and establishing the potential need for higher level of care. It is based on the evaluation of vital signs, including respiratory rate, oxygen saturation, temperature, blood pressure, pulse/heart rate, AVPU response. The resulting observations, compared to a normal range, are combined in a single composite "alarm" score. Any other clinical sign clearly indicating a disease worsening will be considered as disease progression. RANDOMIZATION: Sixty patients will be randomized 2:1 to receive IFN-ß1a plus the standard of care or the standard of care only. Eligible patients will be randomized (no later than 36 h after enrolment) by means of a computerized central randomization system. All patients will receive a unique patient identification number at enrolling visit when signing the informed consent and before any study procedure is performed. This number remains constant throughout the entire study. The randomization of patients will be closed when 60 patients have been enrolled. The randomization will be stratified by sex; for each stratum a sequence of treatments randomly permuted in blocks of variable length (3 or 6) will be generated. BLINDING (MASKING): This is an open-label study. After the randomization, patients will be notified whether they will be in the experimental arm or in the control arm. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study plans to enrol 60 patients: 40 in the IFN-ß1a arm, 20 in the control arm, according to a 2:1 - treated: untreated ratio. TRIAL STATUS: Protocol Version: 3.0 Version Date: 18/03/2021 The study is open for recruitment since 16/04/2021.Recruitment is expected to l be completed before 15/08/2021. TRIAL REGISTRATION: EudraCT N°: 2020-003872-42, registration date: 19/10/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 , HIV Infections , Interferon-beta/therapeutic use , Aged , Clinical Trials, Phase II as Topic , Female , Humans , Male , Randomized Controlled Trials as Topic , Treatment Outcome
9.
J Med Case Rep ; 15(1): 143, 2021 Mar 19.
Article in English | MEDLINE | ID: covidwho-1143254

ABSTRACT

BACKGROUND: There are limited data on cardiovascular complications of coronavirus disease 2019 in pregnancy, and there are only a few case reports on coronavirus disease 2019 related cardiomyopathy in pregnancy. Differentiation between postpartum cardiomyopathy and coronavirus disease 2019 related cardiomyopathy in pregnant women who develop severe acute respiratory syndrome coronavirus-2 infection during peripartum could be challenging. Here, we present a case of possible coronavirus disease 2019 related cardiomyopathy in a pregnant patient, followed by a discussion of potential differential diagnosis. CASE PRESENTATION: In this case report, we present the case of a young pregnant Iranian woman who developed heart failure with pulmonary edema after cesarean section. She was treated because of low left ventricular ejection fraction and impression of postpartum cardiomyopathy, and her severe dyspnea improved by intravenous furosemide. On day 3, she exhibited no orthopnea or leg edema, but she was complaining of severe and dry cough. Further evaluation showed severe acute respiratory syndrome coronavirus-2 infection. CONCLUSIONS: The possibility of severe acute respiratory syndrome coronavirus-2 infection should be considered in any pregnant woman who develops cardiomyopathy and pulmonary edema.


Subject(s)
COVID-19/diagnosis , Cardiomyopathies/diagnosis , Heart Failure/diagnosis , Puerperal Disorders/diagnosis , Pulmonary Edema/diagnosis , Adult , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/physiopathology , COVID-19/therapy , Cardiomyopathies/drug therapy , Cardiomyopathies/physiopathology , Cesarean Section , Cough/physiopathology , Diagnosis, Differential , Diuretics/therapeutic use , Dyspnea/physiopathology , Echocardiography , Electrocardiography , Female , Furosemide/therapeutic use , Heart Failure/drug therapy , Heart Failure/physiopathology , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Lung/diagnostic imaging , Pre-Eclampsia , Pregnancy , Puerperal Disorders/drug therapy , Puerperal Disorders/physiopathology , Pulmonary Edema/drug therapy , Pulmonary Edema/physiopathology , SARS-CoV-2 , Stroke Volume , Tomography, X-Ray Computed
10.
CNS Drugs ; 35(3): 317-330, 2021 03.
Article in English | MEDLINE | ID: covidwho-1141535

ABSTRACT

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). OBJECTIVE: The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. METHODS: The IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. RESULTS: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , African Americans/statistics & numerical data , Aged , Aged, 80 and over , Alemtuzumab/therapeutic use , Azathioprine/therapeutic use , COVID-19/mortality , Cladribine/therapeutic use , Comorbidity , Crotonates/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Databases, Factual , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Hydroxybutyrates , Immunologic Factors/therapeutic use , Incidence , Interferon-beta/therapeutic use , Logistic Models , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Mitoxantrone/therapeutic use , Multiple Sclerosis/epidemiology , Mycophenolic Acid/therapeutic use , Natalizumab/therapeutic use , Nitriles , Obesity/epidemiology , Risk Factors , Rituximab/therapeutic use , SARS-CoV-2 , Toluidines/therapeutic use , United States/epidemiology , Young Adult
11.
Naunyn Schmiedebergs Arch Pharmacol ; 394(5): 829-838, 2021 05.
Article in English | MEDLINE | ID: covidwho-1083109

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 principally weakens the hosts' innate immune system by impairing the interferon function and production. Type I interferons (IFNs) especially IFN-ß are best known for their antiviral activities. IFNs accompanied by the standard care protocols have opened up unique opportunities for treating the coronavirus disease 2019 (COVID-19). The databases including PubMed, SCOPUS, EMBASE, and Google Scholar were searched up to October 30, 2020. The primary and secondary outcomes were considered discharge and mortality, respectively. The abovementioned outcomes of standard care protocol were compared with the standard care plus IFN-ß in the confirmed COVID-19 patients. Out of 356 records identified, 12 randomized clinical trial studies were selected for full-text screening. Finally, 5 papers were included in the systematic review and 3 papers in the meta-analysis. The average mortality rate was reported as 6.195% and 18.02% in intervention and control groups, respectively. Likewise, the median days of hospitalization were lower in the intervention group (9 days) than the control group (12.25 days). According to meta-analysis, IFN-ß was found to increase the overall discharge rate (RR = 3.05; 95% CI: 1.09-5.01). Our findings revealed that early administration of IFN-ß in combination with antiviral drugs is a promising therapeutic strategy against COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Interferon-beta/therapeutic use , Humans , Randomized Controlled Trials as Topic
12.
QJM ; 114(10): 691-697, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1041817

ABSTRACT

Beta interferons (IFN-ß) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-ß preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of 'smart' autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-ß. Here, we present the IFN-ß-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-ß in the treatment of COVID-19 is also briefly discussed.


Subject(s)
COVID-19 , Immunotherapy , Interferon-beta/therapeutic use , Multiple Sclerosis , COVID-19/drug therapy , Humans , Multiple Sclerosis/drug therapy , Pandemics
13.
Int Immunopharmacol ; 92: 107329, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1014566

ABSTRACT

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , HIV Protease Inhibitors/therapeutic use , Interferon-beta/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Drug Combinations , Female , Humans , Interferon-beta/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Retrospective Studies , Ritonavir/administration & dosage , Young Adult
14.
BMJ Case Rep ; 13(12)2020 Dec 17.
Article in English | MEDLINE | ID: covidwho-991776

ABSTRACT

We present the case of a 39-year-old man with epigastric pain, nausea and vomiting. The patient scored 4 in the Visual Triage Checklist of acute respiratory symptoms; a COVID-19 swab was taken. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia and thrombocytopenia. Because the patient had a picture of thrombotic thrombocytopenic purpura, plasma exchange and corticosteroids were started immediately. After 3 days, he developed severe ischaemic stroke and his swabs came back positive for COVID-19 by reverse transcription PCR. Therefore, triple therapy was started (lopinavir/ritonavir, ribavirin and interferon beta-1b). White blood cell count reached 50×109/L (normal range, 4.5-11×109/L), mainly neutrophils. All the workup for autoimmune diseases was negative. The patient showed delayed improvement in lactate dehydrogenase, haemoglobin and platelet count until we increased the volume of plasma exchange and subsided the inflammatory response of COVID-19. After that, the patient showed an excellent recovery.


Subject(s)
COVID-19/diagnosis , Ischemic Stroke/diagnosis , Purpura, Thrombotic Thrombocytopenic/diagnosis , Adult , COVID-19/complications , COVID-19/drug therapy , Drug Combinations , Humans , Interferon-beta/therapeutic use , Ischemic Stroke/etiology , Lopinavir/therapeutic use , Male , Plasma Exchange/methods , Purpura, Thrombotic Thrombocytopenic/etiology , Ritonavir/therapeutic use , SARS-CoV-2
16.
Cell Stem Cell ; 27(6): 869-875.e4, 2020 12 03.
Article in English | MEDLINE | ID: covidwho-927289

ABSTRACT

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon ß-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.


Subject(s)
COVID-19/physiopathology , Respiratory Mucosa/physiopathology , Smoking/adverse effects , Stem Cells/virology , COVID-19/genetics , COVID-19/immunology , COVID-19/therapy , Cells, Cultured , Down-Regulation , Humans , Immunity, Innate , Interferon-beta/therapeutic use , Patient Acuity , Respiratory Mucosa/virology
17.
Curr Opin HIV AIDS ; 15(6): 336-340, 2020 11.
Article in English | MEDLINE | ID: covidwho-817485

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2. RECENT FINDINGS: Recent clinical trials suggested remdesivir, IFN-ß-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive treatment to patients who are late presenters with cytokine storm. Convalescent plasma from recovered COVID-19 patients with high neutralizing antibody might also be beneficial in the treatment of severe disease. SUMMARY: Early effective antiviral therapy in COVID-19 patients will suppress the SARS-CoV-2 viral load. Adjunctive therapy with corticosteroid and convalescent plasma might further ameliorate the cytokine response. Further randomized clinical trials of combination therapy are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Humans , Immunization, Passive , Interferon-beta/therapeutic use , Pandemics , Pneumonia, Viral/immunology , SARS-CoV-2
19.
Med Intensiva (Engl Ed) ; 45(2): 104-121, 2021 Mar.
Article in English, Spanish | MEDLINE | ID: covidwho-733702

ABSTRACT

Infection by the SARS-CoV-2 virus, known as COVID-19 (COronaVIrus Disease-19) was initially detected in China in December 2019, and has subsequently spread rapidly throughout the world, to the point that on March 11 the World Health Organization (WHO) reported that the outbreak could be defined as a pandemic. COVID-19 disease ranges from mild flu-like episodes to other serious and even life-threatening conditions, mainly due to acute respiratory failure. These patients are frequently admitted to our Intensive Care Units in relation to acute respiratory distress syndrome. The lack of a treatment based on scientific evidence has led to the use of different management guidelines, in many cases with rapid changes in the applied protocols. Recent reviews in reputed journals have underscored the lack of proven therapies and the need for clinical trials to establish clear and objective treatment guidelines. The present study provides an update on the currently applied treatment, and intends to offer help in relation to daily care, without seeking to replace the protocols adopted in each individual center.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/therapy , Disease Progression , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Immunomodulation , Interferon-beta/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Nitriles , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines , Ritonavir/therapeutic use
20.
Nat Rev Immunol ; 20(10): 585-586, 2020 10.
Article in English | MEDLINE | ID: covidwho-713702
SELECTION OF CITATIONS
SEARCH DETAIL