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1.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Artículo en Español | MEDLINE | ID: covidwho-749299

RESUMEN

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Inflamación/virología , Neumonía Viral/epidemiología , Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/fisiopatología , Humanos , Hidroxicloroquina/administración & dosificación , Inflamación/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/fisiopatología
3.
J Bras Nefrol ; 42(2 suppl 1): 49-50, 2020 Aug 26.
Artículo en Inglés, Portugués | MEDLINE | ID: covidwho-740468

RESUMEN

Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.


Asunto(s)
Antimaláricos/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Insuficiencia Renal , Brasil , Humanos , Nefrología , Pandemias , Sociedades Médicas
4.
Eur J Med Res ; 25(1): 37, 2020 Aug 27.
Artículo en Inglés | MEDLINE | ID: covidwho-733022

RESUMEN

BACKGROUND: COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases. CASE PRESENTATION: Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment. CONCLUSIONS: An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adulto , Azitromicina/administración & dosificación , Betacoronavirus , Cloroquina/administración & dosificación , Infecciones por Coronavirus/diagnóstico por imagen , Citocinas/metabolismo , Humanos , Inflamación , Masculino , Uso Fuera de lo Indicado , Pandemias , Neumonía Viral/diagnóstico por imagen , Polonia , Tomografía Computarizada por Rayos X
5.
Rev Peru Med Exp Salud Publica ; 37(2): 302-311, 2020.
Artículo en Español | MEDLINE | ID: covidwho-699400

RESUMEN

During the first weeks of 2020, cases of SARS-CoV-2 began to be reported outside of China, with a rapid increase in cases and deaths worldwide. SARS-CoV-2 is a positive single-stranded RNA virus, encased in a lipid bilayer derived from the host cell membrane and consists of four structural proteins (S, M, E and N), plus a haemagglutinin-sterase. The binding of the S protein to the ECA2 receptor allows the entry of the virus into the host cell and is a potential therapeutic target. 81% of patients develop mild symptoms, 14% have severe symptoms and 5% require intensive care management. Fever is the most frequent symptom, followed by cough and dyspnea. Most patients do not present leukocytosis, but they do present lymphopenia with sputum cultures that do not show other pathogens. In lung biopsies of severe patients, the most noticeable finding is diffuse alveolar damage. Radiologically, ground glass and alveolar patterns are observed; the lesions being predominantly basal, subpleural, and posterior, with a multifocal peripheral distribution, more affecting the right lower lobe. There is a marked inflammatory response, up to the cytokine storm, in which anti-inflammatory treatment with pulse therapy with methylprednisolone would be indicated. Although there are no large-scale studies regarding the use of chloroquine / hydroxychloroquine, due to the global situation, its use has been authorized for its anti-SARS-CoV-2 and anti-inflammatory effect, which can be potentiated with the use of azithromycin.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Inflamación/virología , Neumonía Viral/epidemiología , Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/fisiopatología , Humanos , Hidroxicloroquina/administración & dosificación , Inflamación/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/fisiopatología
7.
J Nanosci Nanotechnol ; 20(12): 7311-7323, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: covidwho-680345

RESUMEN

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Betacoronavirus/enzimología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Cisteína Endopeptidasas/química , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/química , Adenina/administración & dosificación , Adenina/análogos & derivados , Adenina/química , Adenina/farmacología , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/química , Adenosina Monofosfato/farmacología , Alanina/administración & dosificación , Alanina/análogos & derivados , Alanina/química , Alanina/farmacología , Amidas/administración & dosificación , Amidas/química , Amidas/farmacología , Antivirales/administración & dosificación , Sitios de Unión , Cloroquina/administración & dosificación , Cloroquina/química , Cloroquina/farmacología , Interacciones Farmacológicas , Humanos , Enlace de Hidrógeno , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/química , Hidroxicloroquina/farmacología , Ligandos , Simulación del Acoplamiento Molecular , Nanotecnología , Pandemias , Inhibidores de Proteasas/administración & dosificación , Pirazinas/administración & dosificación , Pirazinas/química , Pirazinas/farmacología , Pirrolidinas/administración & dosificación , Pirrolidinas/química , Pirrolidinas/farmacología , Ribavirina/administración & dosificación , Ribavirina/química , Ribavirina/farmacología , Electricidad Estática
8.
Int J Antimicrob Agents ; 56(3): 106101, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: covidwho-650831

RESUMEN

The coronavirus infection (COVID-19) has turned into a global catastrophe and there is an intense search for effective drug therapy. Of all the potential therapies, chloroquine and hydroxychloroquine have been the focus of tremendous public attention. Both drugs have been used in the treatment and prophylaxis of malaria. Long-term use of hydroxychloroquine is the cornerstone in the treatment of several auto-immune disorders. There is convincing evidence that hydroxychloroquine has strong in vitro antiviral activity against SARS-CoV-2. A few small uncontrolled trials and several anecdotal reports have shown conflicting results of such drug therapy in COVID-19. However, the results of preliminary large-scale randomized controlled trials have failed to show any survival benefit of such drug therapy in COVID-19. Despite the lack of such evidence, hydroxychloroquine has been used as a desperate attempt for prophylaxis and treatment of COVID-19. The drug has wide-ranging drug interactions and potential cardiotoxicity. Indiscriminate unsupervised use can expose the public to serious adverse drug effects.


Asunto(s)
Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/prevención & control , Hidroxicloroquina/administración & dosificación , Factores Inmunológicos/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/efectos adversos , Antivirales/efectos adversos , Betacoronavirus/efectos de los fármacos , Betacoronavirus/crecimiento & desarrollo , Betacoronavirus/inmunología , Cloroquina/efectos adversos , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Esquema de Medicación , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Hidroxicloroquina/efectos adversos , Factores Inmunológicos/efectos adversos , Pandemias/prevención & control , Neumonía Viral/mortalidad , Neumonía Viral/prevención & control , Neumonía Viral/virología , Análisis de Supervivencia , Internalización del Virus/efectos de los fármacos , Replicación Viral/efectos de los fármacos
9.
Elife ; 92020 07 08.
Artículo en Inglés | MEDLINE | ID: covidwho-636307

RESUMEN

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.


Asunto(s)
Cloroquina/envenenamiento , Sobredosis de Droga/mortalidad , Intento de Suicidio , Suicidio , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/envenenamiento , Antimaláricos/uso terapéutico , Biotransformación , Cloroquina/administración & dosificación , Cloroquina/efectos adversos , Cloroquina/análogos & derivados , Cloroquina/sangre , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Reposicionamiento de Medicamentos , Electrocardiografía , Femenino , Cardiopatías/inducido químicamente , Cardiopatías/mortalidad , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/envenenamiento , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/inducido químicamente , Malaria/tratamiento farmacológico , Masculino , Pandemias , Neumonía Viral/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Medición de Riesgo
10.
Therapie ; 75(4): 335-342, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-622342

RESUMEN

Since December 2019, the COVID-19 pandemic has become a major public health problem. To date, there is no evidence of a higher incidence of COVID in patients with autoimmune rheumatic diseases and we support the approach of maintaining chronic rheumatological treatments. However, once infected there is a small but significant increased risk of mortality. Among the different treatments, NSAIDs are associated with higher rates of complications, but data for other drugs are conflicting or incomplete. The use of certain drugs for autoimmune inflammatory rheumatisms appears to be a potentially interesting options for the treatment. The rationale for their use is based on the immune system runaway and the secretion of pro-inflammatory cytokines (Il1, IL6, TNFα) in severe forms of the disease. Notably, patients on chloroquine or hydroxychloroquine as a treatment for their autoimmune rheumatic disease are not protected from COVID-19.


Asunto(s)
Enfermedades Autoinmunes/epidemiología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Enfermedades Reumáticas/epidemiología , Antiinflamatorios no Esteroideos/administración & dosificación , Antirreumáticos/administración & dosificación , Enfermedades Autoinmunes/tratamiento farmacológico , Cloroquina/administración & dosificación , Infecciones por Coronavirus/mortalidad , Humanos , Hidroxicloroquina/administración & dosificación , Incidencia , Pandemias , Neumonía Viral/mortalidad , Enfermedades Reumáticas/tratamiento farmacológico
14.
Drug Discov Ther ; 14(3): 143-144, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: covidwho-612733

RESUMEN

In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Sistemas de Liberación de Medicamentos/métodos , Canal de Potasio Kv1.3/antagonistas & inhibidores , Linfocitos/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Azitromicina/administración & dosificación , Cloroquina/administración & dosificación , Infecciones por Coronavirus/metabolismo , Citocinas/metabolismo , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Canal de Potasio Kv1.3/metabolismo , Linfocitos/metabolismo , Pandemias , Neumonía Viral/metabolismo , Índice de Severidad de la Enfermedad
19.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(2): 119-122, 2020 Apr 22.
Artículo en Chino | MEDLINE | ID: covidwho-418542

RESUMEN

A novel coronavirus disease (COVID-19) was identified in Wuhan City, Hubei Province of China by the end of 2019, and then, the disease spread across China and became a global pandemic. Nevertheless, there are no effective treatments or vaccines for COVID-19 until now. In addition to the treatment of patients with COVID-19, the China Medical Treatment Expert Group for COVID-19 is active to study and screen effective antiviral drugs, and has found that chloroquine, an old antimalarial,shows activity against SARS-CoV-2. Then, chloroquine was included in the Guidelines for the Diagnosis and Treatment of COVID-19 in China (version 6) issued by National Health Commission of the People's Republic of China. Currently, chloroquine phosphate and hydroxychloroquine sulfate, two chloroquine derivatives, are under clinical use. Although these two agents exhibit similar mechanisms of drug actions, there is a difference between these two chemicals in terms of target populations, therapeutic efficacy and adverse reactions. This paper summarizes the currently available data and experiences from clinical treatment for malaria with chloroquine drugs, so as to provide insights into the more rational use of chloroquine agents for the treatment of COVID-19.


Asunto(s)
Cloroquina/administración & dosificación , Cloroquina/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/farmacología , Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , China , Cloroquina/efectos adversos , Humanos , Pandemias
20.
Ann Intern Med ; 173(4): 287-296, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: covidwho-381743

RESUMEN

BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate, 500 mg once or twice daily, with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.


Asunto(s)
Antivirales/uso terapéutico , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antivirales/administración & dosificación , Betacoronavirus , Cloroquina/administración & dosificación , Humanos , Hidroxicloroquina/administración & dosificación , Pandemias
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