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1.
Acta Biomed ; 91(13-S): e2020009, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33170175

RESUMO

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. METHODS: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. RESULTS: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.


Assuntos
Antivirais/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Endocitose/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Pneumonia Viral/tratamento farmacológico , alfa-Ciclodextrinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Células CACO-2 , Técnicas de Cultura de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Orais , Pandemias , Álcool Feniletílico/efeitos adversos , Projetos Piloto , Adulto Jovem
2.
BMC Infect Dis ; 20(1): 842, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187478

RESUMO

BACKGROUND: Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost. METHODS: Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome. RESULTS: Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19). CONCLUSIONS: Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antivirais/uso terapêutico , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/epidemiologia , Citomegalovirus , Ganciclovir/uso terapêutico , Valganciclovir/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Administração Oral , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Retinite por Citomegalovirus/virologia , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/efeitos adversos , HIV , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Mianmar/epidemiologia , Atenção Primária à Saúde , Estudos Retrospectivos , Resultado do Tratamento , Valganciclovir/administração & dosagem , Valganciclovir/efeitos adversos , Acuidade Visual/efeitos dos fármacos
3.
Intern Med ; 59(22): 2951-2953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33191372

RESUMO

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.


Assuntos
Amidas/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Febre/induzido quimicamente , Pneumonia Viral/tratamento farmacológico , Pirazinas/efeitos adversos , Idoso de 80 Anos ou mais , Amidas/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/epidemiologia , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pirazinas/uso terapêutico
4.
Trials ; 21(1): 906, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138848

RESUMO

OBJECTIVES: - To describe the evolution of the SARS-CoV-2 salivary viral load of patients infected with Covid-19, performing 7 days of tri-daily mouthwashes with and without antivirals. - To compare the evolution of the SARS-CoV-2 nasal and salivary viral load according to the presence or absence of antivirals in the mouthwash. TRIAL DESIGN: This is a multi-center, randomised controlled trial (RCT) with two parallel arms (1:1 ratio). PARTICIPANTS: Inclusion criteria - Age: 18-85 years old - Clinical diagnosis of Covid-19 infection - Clinical signs have been present for less than 8 days - Virological confirmation - Understanding and acceptance of the trial - Written agreement to participate in the trial Exclusion criteria - Pregnancy, breastfeeding, inability to comply with protocol, lack of written agreement - Patients using mouthwash on a regular basis (more than once a week) - Patient at risk of infectious endocarditis - Patients unable to answer questions - Uncooperative patient The clinical trial is being conducted with the collaboration of three French hospital centers: Hospital Center Emile Roux (Le Puy en Velay, France), Clinic of the Protestant Infirmary (Lyon, France) and Intercommunal Hospital Center (Mont de Marsan, France). INTERVENTION AND COMPARATOR: Eligible participants will be allocated to one of the two study groups. Intervention group: patients perform a tri-daily mouthwash with mouthwash containing antivirals (ß-cyclodextrin and Citrox®) for a period of 7 days. CONTROL GROUP: patients perform a tri-daily mouthwash with a placebo mouthwash for a period of 7 days. MAIN OUTCOMES: Primary Outcome Measures: Change from Baseline amount of SARS-CoV-2 in salivary samples at 4 and 9 hours, 1, 2, 3, 4, 5 and 6 days. Real-time PCR assays are performed to assess salivary SARS-CoV 2 viral load. SECONDARY OUTCOME MEASURES: Change from Baseline amount of SARS-CoV-2 virus in nasal samples at 6 days. Real-time PCR assays are performed to assess nasal SARS-CoV-2 viral load. RANDOMISATION: Participants meeting all eligibility requirements are allocated to one of the two study arms (mouthwash with ß-cyclodextrin and Citrox® or mouthwash without ß-cyclodextrin and Citrox®) in a 1:1 ratio using simple randomisation with computer generated random numbers. BLINDING (MASKING): Participants, doctors and nurses caring for participants, laboratory technicians and investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Both the intervention and control groups will be composed of 103 participants, so the study will include a total of 206 participants. TRIAL STATUS: The current protocol version is 6, August 4th, 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. As of October 2, 2020, forty-two participants have been included. TRIAL REGISTRATION: This trial was registered on 20 April 2020 at www.clinicaltrials.gov with the number NCT04352959 . 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." The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2)."


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus , Antissépticos Bucais , Cavidade Nasal/virologia , Pandemias , Pneumonia Viral , Saliva/virologia , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Antissépticos Bucais/administração & dosagem , Antissépticos Bucais/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Carga Viral , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/efeitos adversos
5.
Biomedica ; 40(Supl. 2): 80-95, 2020 10 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33152192

RESUMO

Introduction: Recently, researchers from China and France reported on the effectiveness of chloroquine and hydroxychloroquine for the inhibition of SARS-CoV-2 viral replication in vitro. Timely dissemination of scientific information is key in times of pandemic. A systematic review of the effect and safety of these drugs on COVID-19 is urgently needed. Objective: To map published studies until March 25, 2020, on the use of chloroquine and its derivates in patients with COVID-19. Materials and methods: We searched on PubMed, Embase, Lilacs, and 15 registries from the World Health Organization's International Clinical Trials Registry Platform for theoretical and empirical research in English, Spanish, Italian, French, or Portuguese until March 25, 2020, and made a narrative synthesis of the results. Results: We included 19 records and 24 trial registries (n=43) including 18,059 patients. China registered 66% (16/24) of the trials. Nine trials evaluate chloroquine exclusively and eight hydroxychloroquine. The records are comments (n=9), in vitro studies (n=3), narrative reviews (n=2), clinical guidelines (n=2), as well as a systematic review, an expert consensus, and a clinical trial. Conclusions: One small (n=26), non-randomized, and flawed clinical trial supports hydroxychloroquine use in patients with COVID-19. There is an urgent need for more clinical trial results to determine the effect and safety of chloroquine and hydroxychloroquine on COVID-19.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/farmacologia , Betacoronavirus/fisiologia , Cloroquina/efeitos adversos , Cloroquina/farmacologia , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo , Síndrome da Liberação de Citocina/tratamento farmacológico , Reposicionamento de Medicamentos , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
6.
Trials ; 21(1): 904, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129363

RESUMO

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 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.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pirazinas/uso terapêutico , Amidas/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hidroxicloroquina/efeitos adversos , Pacientes Internados , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento
7.
Eur Rev Med Pharmacol Sci ; 24(18): 9739-9743, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33015819

RESUMO

OBJECTIVE: Remdesivir is a nucleotide analogue prodrug that inhibits viral RNA polymerases. It has been recognized recently as a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV5). We aimed at determining which drugs used in dentistry interact with Remdesivir in order to avoid adverse reactions that may worsen the condition of patients with COVID-19. MATERIALS AND METHODS: A literature review was conducted to identify potential drug interactions between remdesivir (used in the treatment of COVID-19) and drugs prescribed in dentistry. The search was made in the databases PubMed and MEDLINE and official websites using key terms remdesivir, drug interactions and dentistry for articles published up to 31st July 2020. RESULTS: According to the articles reviewed, a total of 279 drugs interact with Remdesivir. Two major interactions have been reported, 277 moderate drug interactions, and one with alcohol/food. The drug interactions involving drugs prescribed in dentistry are all moderate drug interactions and are (according to drug group): (1) antibiotics: azithromycin, clavulanate, doxycycline, erythromycin, levofloxacin; (2) antifungals: clotrimazole, fluconazole, itraconazole, ketoconazole; (3) non-steroidal anti-inflammatories (NAIDS): celecoxib diclofenac, etodolac, flurbiprofen, ibuprofen, ketoprofen, ketorolac, mefenamic acid, naproxen, piroxicam. CONCLUSIONS: It is clinically necessary for oral health professionals to be aware of possible drug interactions that may occur between remdesivir and drugs commonly prescribed in dentistry in order to prevent adverse reactions that may even endanger the life of a patient with COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus , Odontologia , Interações Medicamentosas , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos , Pneumonia Viral/tratamento farmacológico
8.
Medicine (Baltimore) ; 99(41): e22650, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031326

RESUMO

RATIONALE: Hepatitis B virus (HBV) reactivation caused by immunosuppressive therapy or chemotherapy is well known. The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has also been reported to cause HBV reactivation. We report a rare case of HBV reactivation in a patient with HCV infection after DAA therapy. PATIENT CONCERNS: In 1996, a 53-year-old female was identified as infected with HCV at a medical check-up, following which she visited our hospital. She was infected with HCV genotype 2b, and at follow up in 1997, was found to be hepatitis B surface antigen (HBsAg) and antibody against HBsAg negative, antibody against HBV core positive. She then experienced malignant lymphoma in 2001 at 58 years of age. Complete remission was achieved following chemotherapy and autologous peripheral blood stem cell transplantation. In 2014, she remained negative for HBsAg and antibody against HBsAg but positive for antibody against HBV core. In 2015, 12 weeks of sofosbuvir and ribavirin treatment for HCV was started. Serum HCV RNA levels rapidly decreased, and HCV elimination was confirmed at 24 weeks after cessation of DAA treatment. Acute hepatitis B developed at 15 weeks post- sustained virological response without any symptoms and physical examination findings. DIAGNOSES: This case is speculated to represent HBV reactivation induced by DAA treatment in a patient with previously resolved HBV, based on virologic and clinical status. Genome sequencing revealed the HBV genotype as A2. INTERVENTIONS: The patient was treated with nucleotide analog for HBV reactivation once a day. OUTCOMES: Serum HBV-DNA levels decreased, and serum liver enzymes improved following initiation of nucleotide analog treatment. Also, adverse events of nucleotide analog treatment were not observed. LESSONS: Although the risk may be very low, DAA therapy can cause HBV reactivation in chronic hepatitis C patients with prior HBV infection. Thus, those patients must be closely monitored for serum HBV DNA levels during and after DAA treatment.


Assuntos
Antivirais/efeitos adversos , Vírus da Hepatite B/isolamento & purificação , Hepatite C/tratamento farmacológico , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Feminino , Hepatite B/virologia , Humanos , Pessoa de Meia-Idade , Recidiva
9.
Zhonghua Gan Zang Bing Za Zhi ; 28(10): 831-837, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-33105927

RESUMO

Objective: To understand the effectiveness and safety sofosbuvir/velpatasvir (SOF/VEL) combination ±ribavirin in the treatment of chronic hepatitis C virus (HCV) infection in China. Methods: A total of 96 Chinese adults with chronic HCV infection who were treated with SOF/VEL combination ± ribavirin for 12 weeks between July 2018 and February 2020 were selected. HCV RNA, routine blood test, liver, kidney and coagulation function, abdominal Color Doppler ultrasound or CT and liver stiffness were detected at baseline, 4 weeks of treatment, end of treatment and 12 weeks of follow-up. Adverse events and laboratory abnormalities during the treatment were recorded. A t-test was used to compare the measurement data between the two groups, and the analysis of variance was used for multiple group comparison. Results: A total of 93 cases (96.9%) achieved sustained virological response (SVR12), of which 3 cases had relapsed. 88 cases (91.7%, 88/96) had achieved rapid virological response (RVR). 96 cases (100%) had achieved virological response by the end of treatment (EOT). In patients with decompensated liver cirrhosis, the average baseline Child-Pugh score and Model for End-Stage Liver Disease score was 7.4±1.0, and 11.4±1.7, respectively. Among them, 12 cases of the SOF/VEL combined with RBV treatment had achieved SVR12 (100%) at 12 weeks, while only 3 of the 5 cases of single-tablet regimen of SOF/VEL had achieved SVR12 (60%). There was no significant difference between creatinine levels and baseline during or 12 weeks after treatment. The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 6.3% (5/79), while that in patients with decompensated cirrhosis was 35.3% (6/17). The most common adverse events were hyperbilirubinemia, fatigue and anemia. There were no serious adverse events, deaths or discontinuation of treatment due to adverse events. Conclusion: SOF/VEL combination ± ribavirin in the treatment of various common genotypes of chronic hepatitis C, compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma has higher SVR12 in China, and the tolerance and safety are good.


Assuntos
Antivirais/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C Crônica , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , China , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Cirrose Hepática/virologia , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Resultado do Tratamento
10.
Trials ; 21(1): 886, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109246

RESUMO

OBJECTIVES: We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. INCLUSION CRITERIA: 1. Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. 2. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. 3. Hospitalized ≤ 48 h. 4. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. 2. Severe and critical COVID-19 pneumonia. 3. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. 4. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day. CONTROL GROUP: lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups. MAIN OUTCOMES: The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O2 saturation within 7 days of randomization. The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7 days of randomization. RANDOMIZATION: Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group). TRIAL STATUS: The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3 . Registered on 22 July 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 the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Assuntos
Amidas , Infecções por Coronavirus , Quimioterapia Combinada/métodos , Interferons , Lopinavir , Pandemias , Pneumonia Viral , Pirazinas , Ritonavir , Adulto , Amidas/administração & dosagem , Amidas/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Interferons/administração & dosagem , Interferons/efeitos adversos , Irã (Geográfico) , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral/métodos
11.
J Perinat Med ; 48(9): 1001-1007, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33055313

RESUMO

Objectives The severe acute respiratory syndrome coronavirus 2 (COVID-19) outbreak in Italy, especially in Lombardy and Bergamo city, represented probably nowadays one of the first major clusters of COVID-19 in the world. The aim of this report is to describe the activity of Bergamo Teratology Information Service (TIS) in supporting the public and health-care personnel in case of drug prescriptions in suspected/confirmed COVID-19 pregnant and lactating patients during COVID-19 outbreak in Italy. Methods All Bergamo TIS requests concerning COVID-19 pregnant and lactating women have been retrospectively evaluated from 1 March to 15 April 2020. Type of medications, drug's safety profile and compatibility with pregnancy and lactation are reported. Results Our service received information calls concerning 48 (9 pregnant, 35 lactating) patients. Among pregnant and lactating women, the requests of information were related to 16 and 60 drugs prescriptions respectively. More than half concerned drugs prescriptions during the first and second trimester (13/16) and during the first six months of lactation (37/60). Hydroxychloroquine and azithromycin were the most involved. Conclusions Hydroxychloroquine and azithromycin at dosages used for COVID-19 may be considered compatible and reasonably safe either in pregnancy and lactation. Antivirals may be considered acceptable in pregnancy. During lactation lopinavir and ritonavir probably exhibit some supportive data from literature that darunavir and cobicistat do not. Tocilizumab may be considered for COVID-19 treatment because no increased malformation rate were observed until now. However caution may be advised because human data are limited and the potential risk of embryo-fetal toxicity cannot be excluded.


Assuntos
Antivirais/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Lactação , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Anormalidades Induzidas por Medicamentos , Adulto , Azitromicina/efeitos adversos , Anormalidades Congênitas , Prescrições de Medicamentos , Feminino , Idade Gestacional , Humanos , Hidroxicloroquina/efeitos adversos , Itália , Troca Materno-Fetal , Pessoa de Meia-Idade , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Teratologia
13.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
14.
Trials ; 21(1): 847, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050947

RESUMO

OBJECTIVES: Primary objective: To determine the efficacy of a candidate antiviral on time to virological cure compared to standard of care within 14 days of randomisation Secondary objectives: • To determine the safety of the antiviral • To determine the clinical benefit of the antiviral over placebo according to the WHO 7-point ordinal scale • To determine the clinical benefit of the antiviral over placebo on time to resolution of clinical symptoms • To determine the effect of the antiviral over placebo on biomarkers of inflammation and immune activation TRIAL DESIGN: This is a multi-centre, triple-blind, randomised placebo controlled phase II, 2-arm trial with parallel-group design with allocation ratio 1:1. PARTICIPANTS: Inclusion Criteria: • Provision of informed consent by the participant • Age ≥18 years • Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days • COVID-19 related symptom initiation within 5 days • Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. EXCLUSION CRITERIA: • Known allergy to the study medication • Is on another clinical trial investigating an antiviral treatment for COVID-19 • Pregnancy • Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification • Patients with renal impairment requiring dialysis • Is deemed by the Investigator to be ineligible for any reason Participants will be recruited from, and the study visits will take place at Alfred Hospital, Monash Health, Austin Health in Victoria, Australia for hospitalised participants as well as recruitment in the community in participants homes for eligible people not requiring hospitalisation. INTERVENTION AND COMPARATOR: The first candidate antiviral is favipiravir Arm 1: Favipiravir 1800 mg favipiravir BD on Day 1 followed by 800 mg BD favipiravir for the next 13 days. Arm 2: Placebo MAIN OUTCOMES: Primary outcome: Time to virological cure as defined by 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing during the 14 days after enrolment. RANDOMISATION: Randomisation performed at the Alfred Hospital Clinical Trials Pharmacy using computer generated block-randomisation lists with 6 participants per block. Within each block half of the participants will be randomised to the candidate antiviral and the other half to placebo. Randomisation is stratified by study site, with participants enrolled in the community considered as a study site. BLINDING (MASKING): Study participants, study investigators and the study statistician will be blinded to treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study aims to recruit 190 people (95/arm) with the first candidate antiviral favipiravir TRIAL STATUS: Protocol version 2.0 Dated 31-Jul-2020. Recruitment will take place between July 2020 and December 2020. TRIAL REGISTRATION: clinicaltrials.gov NCT04445467 First posted 24-Jun-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.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pirazinas/uso terapêutico , Amidas/efeitos adversos , Antivirais/efeitos adversos , Austrália/epidemiologia , Betacoronavirus/genética , Biomarcadores/metabolismo , Protocolos Clínicos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pandemias , Placebos/administração & dosagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Pirazinas/efeitos adversos , Segurança , Resultado do Tratamento
15.
Front Immunol ; 11: 2167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013911

RESUMO

The inflammatory response to and the subsequent development of Adult Respiratory Distress Syndrome (ARDS) is considered to underpin COVID-19 pathogenesis. With a developing world catastrophe, we need to examine our known therapeutic stocks, to assess suitability for prevention and/or treatment of this pro-inflammatory virus. Analyzing commonly available and inexpensive immunomodulatory and anti-inflammatory medications to assess their possible effectiveness in improving the host response to COVID-19, this paper recommends the following: (1) optimize current health-cease (reduce) smoking, ensure adequate hypertension and diabetes control, continue exercising; (2) start on an HMG CoA reductase inhibitor "statin" for its immunomodulatory and anti-inflammatory properties, which may reduce the mortality associated with ARDS; and (3) consider using Diclofenac (or other COX-2 inhibition medications) for its anti-inflammatory and virus toxicity properties. For purposes of effectiveness, this needs to be in the early course of the disease (post infection and/or symptom presentation) and given in a high dose. The downsides to these recommended interventions are considered manageable at this stage of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/prevenção & controle , Síndrome do Desconforto Respiratório do Adulto/virologia , Internalização do Vírus/efeitos dos fármacos
16.
Trials ; 21(1): 827, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008479

RESUMO

OBJECTIVES: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-to: KT) and shosaikotokakikyosekko (sho-saiko-to-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-to-moderate COVID-19 patients compared to those treated only with conventional treatment. TRIAL DESIGN: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-arm study. PARTICIPANTS: Patients and inpatients will be recruited from 8 Japanese academic and non-academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: 1. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2. Clinical stages of mild-to-moderate COVID-19 3. Symptomatic 4. ≥ 20 years of age 5. Male or female 6. Ability to communicate in Japanese 7. Outpatients and inpatients 8. Provided informed consent Exclusion criteria: 1. Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms 2. Allergic to Kampo or Western medicines used in this study 3. Pregnant and lactating 4. Unable to follow up 5. Participating in another clinical trial or interventional study 6. Hypokalemic or taking oral furosemide or steroids 7. Determined unsuitable for this study by the physician INTERVENTION AND COMPARATOR: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. MAIN OUTCOMES: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. RANDOMIZATION: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. BLINDING (MASKING): Open-label with no blinding NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients' symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). TRIAL STATUS: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs021200020 . Registered on August 25, 2020 FULL PROTOCOL: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Kampo , Pneumonia Viral/tratamento farmacológico , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Interações Hospedeiro-Patógeno , Humanos , Japão , Masculino , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
18.
Expert Opin Investig Drugs ; 29(11): 1195-1198, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32896184

RESUMO

INTRODUCTION: In clinical trial for the Ebola virus, the broad-spectrum anti-viral agent remdesivir was shown to have a good safety profile. Remdesivir is now being tested in severe COVID-19. AREAS COVERED: The Gilead Sciences SIMPLE trial suggests that the short-term use of remdesivir probably does not increase mortality dramatically or have serious short-term toxicity when used to treat severe COVID-19. The Adaptive COVID-19 treatment trials (ACTT1) trial showed that remdesivir may shorten recovery and decrease mortality in severe COVID-19 without increasing adverse effects. EXPERT OPINION: It seems to me that we have learnt very little from the SIMPLE trial, and this would be predicted from a trial that has no control or placebo group. The results of ACTT1 were reported early after an interim analysis showed that a higher than expected number of recoveries had occurred. There was an indication that remdesivir may be reducing mortality, but this was no statistical significance. The trial is continuing, and the final data are eagerly awaited to determine whether remdesivir is a game-changing remedy or a ripple in the ongoing search for a medicine for the treatment of COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Int Immunopharmacol ; 88: 106869, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889241

RESUMO

BACKGROUND: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. METHODS: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. RESULTS: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. CONCLUSIONS: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interleucina-6/sangue , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
20.
Eur J Med Chem ; 207: 112739, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871342

RESUMO

The Strategic Plan for Biodefense Research by the U.S. Department of Health and Human Services demarcates the need for drugs which target multiple types of pathogens to prepare for infectious threats. Azithromycin is one such broad-spectrum therapeutic that is both included in the University of Oxford's RECOVERY and excluded from the World Health Organization's SOLIDARITY trials. Here we review azithromycin's broad antibiotic, antimalarial, antiviral pharmacology and contextualise it against a broader history as the most repositioned therapeutic of the macrolide class; we further evaluate azithromycin's clinical and socio-economic propriety for respiratory pandemics and delineate a model for its combinatorial mechanism of action against COVID-19 pneumonia.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Animais , Anti-Inflamatórios/efeitos adversos , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Betacoronavirus , Linhagem Celular Tumoral , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Macrófagos/metabolismo , Pandemias
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