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1.
Trials ; 22(1): 4, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397429

RESUMEN

OBJECTIVES: We will evaluate the efficacy and safety of Ivermectin in patients with mild and moderately severe COVID-19. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design (1:1 ratio). PARTICIPANTS: The Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will screen for patients age ≥ 20 years and weight ≥35 kg for the following criteria: Inclusion criteria for patients with mild COVID-19 symptoms (outpatients) 1. Diagnosed mild pneumonia using computed tomography (CT) and/or chest X-ray (CX-R) imaging, not requiring hospitalization. 2. Signing informed consent. Inclusion criteria for patients with moderate COVID-19 symptoms (inpatients) 1. Confirmed infection using PCR. 2. Diagnosed moderate pneumonia using CT and/or CXR imaging, requiring hospitalization. 3. Hospitalized ≤ 48 hours. 4. Signing informed consent. Exclusion criteria 1. Severe and critical pneumonia due to COVID-19. 2. Underlying diseases, including AIDS, asthma, loiasis, and severe liver and kidney disease. 3. Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). 4. History of drug allergy to Ivermectin. 5. Pregnancy or breastfeeding. INTERVENTION AND COMPARATOR: Intervention groups: Outpatient and inpatient groups will receive the standard treatment regimen for mild and moderate COVID-19, based on the Iranian Ministry of Health and Medical Education's protocol, along with oral Ivermectin (MSD Company, France) at a single dose of 0.2 mg/kg. Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days. The inpatient group will receive 200/50 mg Lopinavir/Ritonavir (Heterd Company, India) twice a day for the seven days, plus five doses of 44 mcg Interferon beta-1a (CinnaGen, Iran) every other day. Other supportive and routine care will be the same in both outpatient and inpatient groups. MAIN OUTCOME: The primary outcomes are composite and include the improvement of clinical symptoms and need for hospitalization for outpatient groups, and the length of hospital stay until discharge, the need for ICU admission until discharge, and the need for mechanical ventilation for inpatient groups within seven days of randomization. The secondary outcome is the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Patients in both outpatient (mild) and inpatient (moderate) groups will be randomized into the treatment and control groups based on the following method. A simple randomization method and table of random numbers will be used. If the selected number is even, the patient is allocated to the treatment group, and if it is odd, the patient is allocated to the control group in a 1:1 ratio. BLINDING (MASKING): This is an open-label study, and there is not blinding. Numbers to be randomized (sample size) A total number of 120 patients (60 outpatients and 60 patients) will be randomized into two groups (30 patients in each of the intervention groups and 30 patients in each of the control groups). TRIAL STATUS: The protocol is Version 1.0, November 17, 2020. Recruitment began November 25, 2020, and is anticipated to be completed by February 25, 2021. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N6 ". The registration date is November 17, 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.


Asunto(s)
Antivirales/administración & dosificación , Ivermectina/administración & dosificación , /aislamiento & purificación , Administración Oral , Adulto , Antivirales/efectos adversos , /virología , Ensayos Clínicos Fase III como Asunto , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Interferón beta-1a/administración & dosificación , Interferón beta-1a/efectos adversos , Irán , Ivermectina/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad
2.
Trials ; 22(1): 3, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397457

RESUMEN

OBJECTIVES: To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19. TRIAL DESIGN: This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial. PARTICIPANTS: Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward. INCLUSION CRITERIA: Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening. INTERVENTION AND COMPARATOR: Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria. MAIN OUTCOME MEASURES: Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs. RANDOMISATION: Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities. BLINDING: None, this is an open-label trial. NUMBER TO BE RANDOMISED (SAMPLE SIZE): 98 patients (49 per arm). TRIAL STATUS: Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534 . FULL PROTOCOL: The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in 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).


Asunto(s)
Antivirales/administración & dosificación , Sulfato de Atazanavir/administración & dosificación , Ritonavir/administración & dosificación , Tiazoles/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Sulfato de Atazanavir/efectos adversos , /virología , Ensayos Clínicos Fase II como Asunto , Esquema de Medicación , Combinación de Medicamentos , Reposicionamiento de Medicamentos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nigeria , Proyectos Piloto , ARN Viral/aislamiento & purificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/efectos adversos , /aislamiento & purificación , Índice de Severidad de la Enfermedad , Nivel de Atención , Tiazoles/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Adulto Joven
3.
Eur Rev Med Pharmacol Sci ; 25(1): 549-555, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33506948

RESUMEN

OBJECTIVE: Because of the limited treatment options available, oral lopinavir/ritonavir (LPR) was used for treating coronavirus disease (COVID-19) in pediatric patients. This study aimed to assess the efficacy and safety of LPR in COVID-19 pediatric patients with mild symptoms. PATIENTS AND METHODS: This retrospective multicenter analysis included hospitalized children with mild COVID-19 who received LPR at one of 13 hospitals in China from January 1, 2020, to June 1, 2020. Patients treated with LPR were matched with patients not treated with LPR (1:4) according to age, sex, and length of symptom onset and hospitalization. Descriptive statistics and non-parametric tests were applied to compare differences between groups. Kaplan-Meier probability curves and Cox regression models were used to analyze nasal swab turning negative time (recovery time) and hospital discharge days. RESULTS: In total, 23 patients treated with LPR were matched with 92 untreated controls. The median age of patients was 6 years, and 56.52% of them were male. All patients were discharged from the hospital after being cured. The treatment group had a longer nasal swab turning negative time (hazard ratio [HR] 5.33; 95% CI: 1.94-14.67; p = 0.001) than the control group. LPR treatment was also associated with a longer hospitalization time (HR 2.01; 95% CI: 1.24-3.29; p = 0.005). After adjusting for the influence of LPR treatment, adverse drug reaction events were associated with a longer nasopharyngeal swab negative time (HR 4.67; 95% CI 1.35-16.11; p = 0.015). CONCLUSIONS: For children with mild COVID-19, LPR is inferior to conventional treatment in reducing virus shedding time and hospitalization duration and is associated with increased adverse reactions.


Asunto(s)
Antivirales/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Administración Oral , Antivirales/administración & dosificación , Antivirales/efectos adversos , Niño , China , Quimioterapia Combinada , Femenino , Hospitalización , Humanos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Estudios Retrospectivos , Ritonavir/administración & dosificación , Ritonavir/efectos adversos
4.
Ann Intern Med ; 174(1): JC3, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395331

RESUMEN

SOURCE CITATION: RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396:1345-52. 33031764.


Asunto(s)
Antivirales/uso terapéutico , Hospitalización , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Administración Oral , Anciano , Antivirales/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Lopinavir/administración & dosificación , Masculino , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/administración & dosificación , Reino Unido
5.
Sci Rep ; 11(1): 2169, 2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33500507

RESUMEN

To evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6-10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8+ T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8+ T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8+ T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.


Asunto(s)
Linfocitos T CD8-positivos/virología , Progresión de la Enfermedad , Corticoesteroides/administración & dosificación , Adulto , Algoritmos , China , Femenino , Humanos , Hipoxia/metabolismo , Lopinavir/administración & dosificación , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Oxígeno/química , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Ritonavir/administración & dosificación
6.
Int Immunopharmacol ; 92: 107329, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33412395

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , Interferón beta/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Combinación de Medicamentos , Femenino , Humanos , Interferón beta/administración & dosificación , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ritonavir/administración & dosificación , Adulto Joven
7.
Int J Biol Macromol ; 168: 272-278, 2021 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-33309661

RESUMEN

SARS-CoV-2is the causative agent for the ongoing COVID19 pandemic, and this virus belongs to the Coronaviridae family. The nsp14 protein of SARS-CoV-2 houses a 3' to 5' exoribonuclease activity responsible for removing mismatches that arise during genome duplication. A homology model of nsp10-nsp14 complex was used to carry out in silico screening to identify molecules among natural products, or FDA approved drugs that can potentially inhibit the activity of nsp14. This exercise showed that ritonavir might bind to the exoribonuclease active site of the nsp14 protein. A model of the SARS-CoV-2-nsp10-nsp14 complex bound to substrate RNA showed that the ritonavir binding site overlaps with that of the 3' nucleotide of substrate RNA. A comparison of the calculated energies of binding for RNA and ritonavir suggested that the drug may bind to the active site of nsp14 with significant affinity. It is, therefore, possible that ritonavir may prevent association with substrate RNA and thus inhibit the exoribonuclease activity of nsp14. Overall, our computational studies suggest that ritonavir may serve as an effective inhibitor of the nsp14 protein. nsp14 is known to attenuate the inhibitory effect of drugs that function through premature termination of viral genome replication. Hence, ritonavir may potentiate the therapeutic properties of drugs such as remdesivir, favipiravir and ribavirin.


Asunto(s)
Antivirales/farmacología , Exorribonucleasas/antagonistas & inhibidores , Ritonavir/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Secuencia de Aminoácidos , Antivirales/administración & dosificación , Antivirales/química , Dominio Catalítico , Simulación por Computador , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Exorribonucleasas/química , Exorribonucleasas/genética , Genoma Viral/efectos de los fármacos , Humanos , Simulación de Dinámica Molecular , Pandemias , Ritonavir/administración & dosificación , Ritonavir/química , /fisiología , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genética , Replicación Viral/efectos de los fármacos
8.
J Interferon Cytokine Res ; 40(12): 578-588, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33337933

RESUMEN

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.


Asunto(s)
/terapia , Interferón alfa-2/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cloroquina/administración & dosificación , Comorbilidad , Cuidados Críticos , Cuba/epidemiología , Quimioterapia Combinada , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Lopinavir/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ritonavir/administración & dosificación , Resultado del Tratamiento , Adulto Joven
9.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-33372741

RESUMEN

We report the case of a man affected by cystic fibrosis who developed a severe SARS-CoV-2 related pneumonia in March 2020. In addition to lopinavir/ritonavir and hydroxychloroquine, he was treated with two doses of tocilizumab, displaying a significant clinical improvement. This is the first case described in the literature of an adult patient affected by cystic fibrosis who received tocilizumab for COVID-19, with documented total recovery, also assessed by a spirometry.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Fibrosis Quística , Hidroxicloroquina/administración & dosificación , Lopinavir/administración & dosificación , Neumonía Viral , Infecciones del Sistema Respiratorio/microbiología , Ritonavir/administración & dosificación , /aislamiento & purificación , Adulto , Antivirales/administración & dosificación , /diagnóstico , /fisiopatología , Fibrosis Quística/complicaciones , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Combinación de Medicamentos , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Terapia por Inhalación de Oxígeno/métodos , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/etiología , Receptores de Interleucina-6/antagonistas & inhibidores , Pruebas de Función Respiratoria/métodos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/etiología , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
10.
Swiss Med Wkly ; 150: w20446, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33382449

RESUMEN

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.


Asunto(s)
Antivirales/uso terapéutico , /epidemiología , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Ritonavir/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/administración & dosificación , Antivirales/efectos adversos , Niño , Preescolar , Comorbilidad , Combinación de Medicamentos , Quimioterapia Combinada , Gastos en Salud , Mortalidad Hospitalaria/tendencias , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Lactante , Tiempo de Internación/estadística & datos numéricos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores Socioeconómicos , Terapias en Investigación/métodos , Adulto Joven
11.
Reumatismo ; 72(3): 173-177, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213130

RESUMEN

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.


Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adalimumab/administración & dosificación , Adulto , Antivirales/administración & dosificación , Artritis Reumatoide/complicaciones , Azatioprina/administración & dosificación , Terapia Biológica , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Combinación de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Lopinavir/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Oseltamivir/administración & dosificación , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Prednisolona/administración & dosificación , Ritonavir/administración & dosificación
13.
Trials ; 21(1): 880, 2020 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-33106183

RESUMEN

OBJECTIVES: We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial. PARTICIPANTS: The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-ß 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences. INTERVENTION AND COMPARATOR: COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-ß 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-ß 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation. MAIN OUTCOMES: Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. SECONDARY OUTCOMES: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. RANDOMIZATION: Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra). TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20th 2020, and the end date was on September 4th 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials ( www.clinicaltrials.gov ; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400 , registered August 18, 2020 and first available online August 20, 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.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Interferón beta-1a/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Antivirales/administración & dosificación , Estudios de Casos y Controles , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Humanos , Interferón beta-1a/administración & dosificación , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Mortalidad/tendencias , Evaluación de Resultado en la Atención de Salud , Pandemias , Alta del Paciente , Neumonía Viral/epidemiología , Neumonía Viral/virología , Respiración Artificial/estadística & datos numéricos , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico
14.
Trials ; 21(1): 886, 2020 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-33109246

RESUMEN

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.


Asunto(s)
Amidas , Infecciones por Coronavirus , Quimioterapia Combinada/métodos , Interferones , Lopinavir , Pandemias , Neumonía Viral , Pirazinas , Ritonavir , Adulto , Amidas/administración & dosificación , Amidas/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Combinación de Medicamentos , Monitoreo de Drogas/métodos , Femenino , Humanos , Interferones/administración & dosificación , Interferones/efectos adversos , Irán , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Carga Viral/métodos
15.
Medicine (Baltimore) ; 99(43): e22920, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33120844

RESUMEN

RATIONALE: Reversible splenial lesion syndrome (RESLES) is a recently identified clinico-radiological syndrome, the etiology is miscellaneous. Atrial septal defect (ASD) as an underlying etiology for RESLES has not been reported. We first report a rare case of RESLES associated with ASD. The clinical, radiological, and ultrasonic profiles were presented and the pathophysiological mechanism was analyzed. PATIENT CONCERNS: A 23-year-old man presented with headache, drowsiness, occasional paraphasia, and paroxysmal dry cough. Brain magnetic resonance imaging (MRI) on admission showed an ovoid isolated lesion in the splenium of corpus callosum, which exhibited hyperintensity on diffusion-weighted imaging and hypointensity on apparent diffusion coefficient, and completely disappeared on the follow-up MRI 14 days later. ASD was found by transthoracic echocardiography, Right-to-left shunts were detected on color Doppler of transesophageal echocardiography, and microemboli were captured by transcranial Doppler ultrasound. DIAGNOSES: According to his clinical history and imaging results, we confirmed the diagnosis of RESLES associated with ASD. INTERVENTIONS: The patient was treated by oral aspirin and lopidogrel sulfate to inhibit platelet aggregation. In addition, oral nimodipine to suppress vasoconstriction. OUTCOMES: After 14 days treatment, all the symptoms presenting on admission resolved completely. Subsequently, a repair surgery of ASD under thoracoscopy was successfully performed. LESSONS: To our knowledge, this is the first reported case of ASD may be an underlying etiology for RESLES and need require an etiotropic treatment.


Asunto(s)
Encefalopatías/etiología , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Defectos del Tabique Interatrial/complicaciones , Administración Oral , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Cuerpo Calloso/patología , Combinación de Medicamentos , Quimioterapia Combinada , Ecocardiografía/métodos , Estudios de Seguimiento , Cefalea/etiología , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/tratamiento farmacológico , Defectos del Tabique Interatrial/cirugía , Humanos , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Masculino , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , Síndrome , Resultado del Tratamiento , Ultrasonografía Doppler Transcraneal/métodos , Adulto Joven
16.
Trials ; 21(1): 866, 2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33081849

RESUMEN

OBJECTIVES: 1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. PARTICIPANTS: The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria. INCLUSION CRITERIA (ALL REQUIRED): 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Treatment Arm Drug A Standard Treatment (STNS) B Hydroxychloroquine 400 mg twice on first day followed by 400 mg per oral daily for 10 days + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STNS) Standard Treatment for non-severe cases (STNS): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. SEVERE GROUP TREATMENT ARMS (S-GROUP): Treatment Arm Drug A Standard Treatment (STs) B Hydroxychloroquine 400mg BD on day1 followed by 400 mg once daily + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs) C Lopinavir(200mg) + Ritonavir (50mg) two tablets twice daily+ Ribavirin (1.2g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs)6 Standard Treatment for severe patients (STs): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (As required), Invasive ventilation (As required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. MAIN OUTCOMES: Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer. RANDOMIZATION: The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. BLINDING (MASKING): This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included. TRIAL STATUS: Protocol version:1.0 Recruitment start: June 3rd, 2020 (Ongoing) Recruitment finish (expected): October 31st, 2020 TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI): CTRI/2020/06/025575 . Registration on 03 June 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.


Asunto(s)
Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Ribavirina/uso terapéutico , Administración Oral , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Antivirales/administración & dosificación , Betacoronavirus/genética , Protocolos Clínicos , Terapia Combinada , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , India/epidemiología , Consentimiento Informado , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Masculino , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Ribavirina/administración & dosificación , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , Seguridad , Factores de Tiempo , Resultado del Tratamiento
17.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871902

RESUMEN

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Asunto(s)
Azitromicina/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus , Exantema , Glucocorticoides/administración & dosificación , Hidroxicloroquina/administración & dosificación , Lopinavir/administración & dosificación , Pandemias , Neumonía Viral , Ritonavir/administración & dosificación , Administración Tópica , Adulto , Antivirales/administración & dosificación , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Combinación de Medicamentos , Exantema/diagnóstico , Exantema/tratamiento farmacológico , Exantema/etiología , Exantema/inmunología , Femenino , Humanos , Neumonía Viral/diagnóstico , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Evaluación de Síntomas/métodos , Resultado del Tratamiento
18.
J Infect Chemother ; 26(12): 1319-1323, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32893123

RESUMEN

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Guanidinas/administración & dosificación , Hemodiafiltración/métodos , Hidroxicloroquina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antivirales/administración & dosificación , Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Combinación de Medicamentos , Humanos , Japón , Lopinavir/administración & dosificación , Masculino , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Insuficiencia Respiratoria/complicaciones , Ritonavir/administración & dosificación , Resultado del Tratamiento
19.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-32919428
20.
Toxicol Appl Pharmacol ; 406: 115237, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32920000

RESUMEN

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.


Asunto(s)
Betacoronavirus , Simulación por Computador , Minería de Datos/métodos , Toxicogenética/métodos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/genética , Bases de Datos Genéticas , Quimioterapia Combinada , Redes Reguladoras de Genes/efectos de los fármacos , Redes Reguladoras de Genes/genética , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/genética , Ritonavir/administración & dosificación , Ritonavir/efectos adversos
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