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Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 565-570, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879108


OBJECTIVES: To evaluate curative effects of coronavirus disease 2019 (COVID-19) patients by the transfusion of other convalescent plasma. METHODS: Retrospective analysis of the clinical data of 18 patients with severe and critical COVID-19, who were hospitalized in the ICU of Xianghu Branch of the First Affiliated Hospital of Nanchang University from February 1 to March 15, 2020. Patients were subdivided into an experimental group (n=6, who had transfused the plasma) and an observation group (n=12, who had no plasma transfusion). Basic clinical data and prognosis indexes of these two groups were compared. Moreover, for the experimental group, the dynamic changes of blood oxygen saturation before and after the transfusion, the changes of lymphocyte absolute value 48 hours after the transfusion, and the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid were analyzed. RESULTS: There were no significant differences in age, gender, blood type and other basic clinical data between the two groups (all P>0.05).There were no significant differences in ventilator machine weaning time, extracorporeal membrane oxygenation (ECMO) weaning time, body temperature recovery to normal time, and hospitalization days between these two groups (all P>0.05). For the experimental group, before, during and after the convalescent plasma transfusion, the blood oxygen saturation of all 6 patients at all time (1, 6, 8, 12, 24, 36, and 48 h) was more than 90%, and there was no significant fluctuation. There were 3 patients whose absolute value of lymphocyte was increased 48 hours after the transfusion, and the remaining was decreased. There were 5 patients whose SARS-CoV-2 nucleic acid detection turned negative 48 hours after the transfusion, accounting for 83.3%. CONCLUSIONS: Transfusion of convalescent plasma will not affect outcomesof COVID-19 patients, which can neutralize SARS-CoV-2 in patients and reduce the loading capacity of SARS-CoV-2.

Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Betacoronavirus , Transfusão de Componentes Sanguíneos , China , Humanos , Imunização Passiva , Pandemias , Plasma , Estudos Retrospectivos
Am J Case Rep ; 21: e926623, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32807764


BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.

Betacoronavirus , Infecções por Coronavirus/complicações , Empiema Pleural/virologia , Inibidor de Coagulação do Lúpus/sangue , Pneumonia Viral/complicações , Adulto , Antifibrinolíticos/uso terapêutico , Cardiolipinas/imunologia , Tubos Torácicos , Infecções por Coronavirus/diagnóstico , Empiema Pleural/diagnóstico por imagem , Empiema Pleural/terapia , Humanos , Imunoglobulina M/sangue , Coeficiente Internacional Normatizado , Masculino , Pandemias , Tempo de Tromboplastina Parcial , Plasma , Pneumonia Viral/diagnóstico , Tempo de Protrombina , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/prevenção & controle , Vitamina K/uso terapêutico
BMC Res Notes ; 13(1): 372, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762746


OBJECTIVE: COVID19 has caused a global and ongoing pandemic. The need for population seroconversion data is apparent to monitor and respond to the pandemic. Using a lateral flow assay (LFA) testing platform, the seropositivity in 63 New York Blood Center (NYBC) Convelescent Plasma (CP) donor samples were evaluated for the presence of COVID19 specific IgG and IgM. RESULTS: CP donors showed diverse antibody result. Convalescent donor plasma contains SARS-CoV-2 specific antibodies. Weak antibody bands may identify low titer CP donors. LFA tests can identify antibody positive individuals that have recovered from COVID19. Confirming suspected cases using antibody detection could help inform the patient and the community as to the relative risk to future exposure and a better understanding of disease exposure.

Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Doadores de Sangue , Técnicas de Laboratório Clínico/métodos , Convalescença , Infecções por Coronavirus/diagnóstico , Imunoensaio/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Proteínas do Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral/diagnóstico , Testes Imediatos , Glicoproteína da Espícula de Coronavírus/imunologia , Especificidade de Anticorpos , Infecções por Coronavirus/terapia , Coloide de Ouro , Humanos , Imunização Passiva , Plasma , Domínios Proteicos , Proteínas Recombinantes/imunologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Soroconversão
Caracas; Observatorio Nacional de Ciencia, Tecnología e Innovación; ago. 2020. 53-56 p. ilus.(Observador del Conocimiento. Revista Especializada en Gestión Social del Conocimiento, 5, 2).
Monografia em Espanhol | LILACS, LIVECS | ID: biblio-1118410


El uso de Plasma de Convaleciente de COVID-19 (PC-CoV19) como coadyuvante en el tratamiento de pacientes, tendría impacto socioeconómico importante al disminuir el periodo de estancia hospitalaria y letalidad por la enfermedad. La determinación de anticuerpos en plasma de potenciales donantes es criterio fundamental para su selección. Existe dificultad para disponer de pruebas serológicas certificadas que cuantifiquen anticuerpos específicos contra SARS-CoV-2. Las Pruebas de Diagnóstico Rápido (PDR) se convierten en herramienta útil y al alcance para la selección de pacientes recuperados, potenciales donantes de PC-CoV19. Este estudio evaluó el porcentaje de positividad de diferentes PDR en veintidós (22) muestras de pacientes con COVID-19 confirmada por RT-PCR. Las muestras se analizaron siguiendo el procedimiento descrito por cada fabricante. Se analizó el comportamiento de las PDR en pacientes sintomáticos y asintomáticos en diferentes momentos de la enfermedad. El porcentaje de positividad fue de 100% con dos de las tres pruebas utilizadas, una de las cuales discrimina IgM de IgG. Se concluye que la presencia de IgG se registra a partir de los 15 días del inicio de los síntomas y se mantiene presente a los 59 días de evolución en los pacientes sintomáticos, y que pacientes asintomáticos podrían ser considerados candidatos a donantes de PC-CoV19 pues se evidenció seroconversión para IgG. El porcentaje de positividad a IgG podría disminuir en los pacientes recuperados. Se sugiere que pacientes sintomáticos con criterio de alta médica sean considerados candidatos donantes en momento posterior a 28 días de la fecha de inicio de los síntomas. Se recomienda utilizar PDR que discriminen IgM de IgG como herramienta para la selección de donantes de PC-CoV19(AU)

The use of COVID-19 Convales-cent Plasma (PC-CoV19) as an ad-juvant for the treatment of patients, would have a significant socioeconomic impact by reducing the leng-th of hospital stay and lethality due to the disease. The determination of antibodies in plasma from potential donors is a fundamental criterion for their selection. There is dificulty in obtaining certified serological tests that quantify specific antibodies against SARS-CoV-2. Rapid Diagnostic Tests (PDR) become a useful and accessible tool in the selection of recovered patients, potential PC-CoV19 donors. This study evaluated the positivity rate of different PDRs in twenty two (22) samples from patients with COVID-19 confirmed by RT-PCR. The samples were analyzed following the procedure described by each manufacturer. The performance of PDRs was analyzed in symptomatic and asymptomatic patients at different times of the disease. The positivity rate was 100% with two of the three tests used, one of which discriminates IgM from IgG. It is concluded that the presence of IgG is recorded 15 days after the onset of symptoms and remains present at day 59 of evolution in symptomatic patients, and that asymptomatic patients could be considered candidates for PC-CoV19 donors since IgG se-reconversion was evident. The positivity rate to IgG could decrease in the recovered patients. It is suggested that symptomatic patients with medical discharge criteria be considered donor candidates after 28 days from the date of onset of symptoms. It is recommended to use PDRs that discriminate IgM from IgG as a tool for the selection of PC-CoV19 donors

Humanos , Plasma , Doadores de Tecidos , Imunoglobulina G/uso terapêutico , Imunoglobulina M , Testes Sorológicos , Infecções por Coronavirus , Testes Diagnósticos de Rotina
Washington; PAHO; Aug. 11, 2020. 91 p.
Monografia em Inglês | LILACS, PIE | ID: biblio-1094870


More than 200 therapeutic options or their combinations are being investigated in more than 1,700 clinical trials. In this review we examined 30 therapeutic options. Findings from the RECOVERY Trial showed that low doses of dexamethasone (6 mg of oral or intravenous preparation once daily for 10 days) significantly reduced mortality by one-third in ventilated patients and by one fifth in patients receiving oxygen only. The anticipated RECOVERY. Trial findings and WHO's SOLIDARITY Trial findings both show no benefit via use of hydroxychloroquine and lopinavir/ritonavir in terms of reducing 28-day mortality or reduced time to clinical improvement or reduced adverse events. Currently, there is no evidence of benefit in critical outcomes (i.e. reduction in mortality) from any therapeutic option (though remdesivir is revealing promise as one option based on 2 randomized controlled trials) and that conclusively allows for safe and effective use to mitigate or eliminate the causative agent of COVID-19. Currently, as to ivermectin, we found 1 in vitro study and 4 observational studies that were largely confounded (nonrandomized), and lacked the methodological rigor to allow much confidence in the results. They were pre-print and non-peer reviewed and were judged to be of high risk of bias and very low quality of evidence. The researchers concluded in large part that the findings could be considered hypothesis testing and urged the conduct of large sample sized RCTs to assess any clinical benefit. Currently, as to favipiravir, we found 1 RCT and 2 observational studies. The results were inconclusive for benefits of favipiravir, and sample sizes were small and results came via largely preprints and non-peer reviewed publications. The 2 nonrandomized observational designs revealed sub-optimal methods with no optimal adjustments, masking, or stratification. A recent release by Glenmark announced promising results from a Phase 3 Clinical Trial of favipiravir in patients with mild to moderate COVID-19. A Phase 3 RCT demonstrates statistically significant faster time to clinical improvement with favipiravir treatment compared to control (n=150 patients).

Humanos , Antivirais/uso terapêutico , Plasma/imunologia , Pneumonia Viral/tratamento farmacológico , Ivermectina/uso terapêutico , Dexametasona/uso terapêutico , Metilprednisolona/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pandemias/prevenção & controle , Lopinavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto
Am J Vet Res ; 81(8): 651-655, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32700994


OBJECTIVE: To determine the pharmacokinetics of amantadine after oral administration of single and multiple doses to orange-winged Amazon parrots (Amazona amazonica). ANIMALS: 12 adult orange-winged Amazon parrots (6 males and 6 females). PROCEDURES: A single dose of amantadine was orally administered to 6 birds at 5 mg/kg (n = 2), 10 mg/kg (2), and 20 mg/kg (2) in a preliminary trial. On the basis of the results, a single dose of amantadine (10 mg/kg, PO) was administered to 6 other birds. Two months later, multiple doses of amantadine (5 mg/kg, PO, q 24 h for 7 days) were administered to 8 birds. Heart rate, respiratory rate, behavior, and urofeces were monitored. Plasma concentrations of amantadine were measured via tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameter estimates were determined via noncompartmental analysis. RESULTS: Mean ± SD maximum plasma concentration, time to maximum plasma concentration, half-life, and area under the concentration-versus-time curve from the last dose to infinity were 1,174 ± 186 ng/mL, 3.8 ± 1.8 hours, 23.2 ± 2.9 hours, and 38.6 ± 7.4 µg·h/mL, respectively, after a single dose and 1,185 ± 270 ng/mL, 3.0 ± 2.4 hours, 21.5 ± 5.3 hours, and 26.3 ± 5.7 µg·h/mL, respectively, at steady state after multiple doses. No adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily oral administration of amantadine at 5 mg/kg to orange-winged Amazon parrots maintained plasma concentrations above those considered to be therapeutic in dogs. Further studies evaluating safety and efficacy of amantadine in orange-winged Amazon parrots are warranted.

Amazona , Administração Oral , Amantadina , Animais , Área Sob a Curva , Feminino , Meia-Vida , Masculino , Plasma
Ann Intern Med ; 173(2): JC3, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32687760


SOURCE CITATION: Ye Z, Rochwerg B, Wang Y, et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline. CMAJ. 2020;192:E536-45. 32350002.

Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Imunização Passiva/métodos , Pandemias , Plasma , Pneumonia Viral/imunologia , Índice de Gravidade de Doença
Proc Natl Acad Sci U S A ; 117(29): 17381-17388, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32632018


Adiponectin (Acrp30) is an adipokine associated with protection from cardiovascular disease, insulin resistance, and inflammation. Although its effects are conventionally attributed to binding Adipor1/2 and T-cadherin, its abundance in circulation, role in ceramide metabolism, and homology to C1q suggest an overlooked role as a lipid-binding protein, possibly generalizable to other C1q/TNF-related proteins (CTRPs) and C1q family members. To investigate this, adiponectin, representative family members, and variants were expressed in Expi293 cells and tested for binding to lipids in liposomes using density centrifugation. Binding to physiological lipids were also analyzed using gradient ultracentrifugation, liquid chromatography-mass spectrometry, and shotgun lipidomics. Interestingly, adiponectin selectively bound several anionic phospholipids and sphingolipids, including phosphatidylserine, ceramide-1-phosphate, glucosylceramide, and sulfatide, via the C1q domain in an oligomerization-dependent fashion. Binding to lipids was observed in liposomes, low-density lipoproteins, cell membranes, and plasma. Other CTRPs and C1q family members (Cbln1, CTRP1, CTRP5, and CTRP13) also bound similar lipids. These findings suggest that adiponectin and CTRPs function not only as hormones, but also as lipid opsonins, as may other C1q family proteins.

Adiponectina/metabolismo , Complemento C1q/metabolismo , Fosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adipocinas/metabolismo , Adiponectina/genética , Animais , Ânions , Membrana Celular , LDL-Colesterol , Humanos , Metabolismo dos Lipídeos , Lipidômica , Lipoproteínas/metabolismo , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Opsonizantes/metabolismo , Plasma
J Intensive Care Med ; 35(9): 827-835, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32666875


In the 5 months since initial reports of COVID-19 came to light, the death toll due to SARS-CoV-2 has rapidly increased. The morbidity and mortality of the infection varies based upon patient age, comorbid conditions, viral load, and the availability of effective treatments. Findings from limited autopsies, clinical observations, and laboratory data suggest that high cytokine levels and a procoagulant state can precipitate acute respiratory distress syndrome and multi-organ dysfunction syndrome in critically ill patients. To complicate matters, comorbidities may affect the response to medical treatments currently in use, all of which are still in trial phase. Therapeutic plasma exchange (TPE) merits consideration in the treatment of critically ill COVID-19 patients and is an avenue for clinical trials to pursue. If efficacious, faster recovery of patients may lead to shorter intensive care unit stays and less time on mechanical ventilation. Herein, we briefly discuss some of the various approaches currently being investigated for the treatment of SARS-CoV-2 with a focus on potential benefits of TPE for selected critically ill patients.

Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Estado Terminal/terapia , Troca Plasmática/métodos , Plasma/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus , Humanos , Pandemias
Caracas; Observatorio Nacional de Ciencia, Tecnología e Innovación; 9 jul. 2020. 15-31 p. (Observador del Conocimiento. Revista Especializada en Gestión Social del Conocimiento, 5, 2).
Monografia em Espanhol | LILACS, LIVECS | ID: biblio-1119053


En diciembre 2019, en Wuhan, China, se registró un aumento inusual de casos de infección respiratoria aguda de rápida progresión y alta letalidad. Al poco tiempo es identificado el agente causal, un coronavirus denominado SARS-CoV-2 y se caracteriza una nueva enfermedad, COVID-19. En ausencia hasta el momento de tratamientos específicos, eficaces y seguros, se justifica explorar alternativas científicamente fundamentadas a nuestro alcance como el uso de Plasma de Convaleciente (PC-CoV19) como coadyuvante para el tratamiento de la COVID-19. El plasma de pacientes recuperados de una enfermedad infecciosa, Plasma de Convaleciente, ha sido utilizado en el tratamiento de patologías infecciosas. Hay antecedentes inmediatos de su uso en enfermedades producidas por otro tipo de coronavirus y se registran experiencias y estudios clínicos con resultados preliminares durante esta pandemia. Quimbiotec, empresa productora de hemoderivados y fármacos recombinantes del Estado venezolano, y el Banco Municipal de Sangre, definen un protocolo para promover condiciones para la aféresis, procesamiento, conservación, almacenamiento, distribución, transfusión y evaluación de la seguridad y eficacia del PC-CoV19 como alternativa en el tratamiento de la COVID-19 en Venezuela. Se incluye la identificación de capacidades y de talento, la estructura física, equipos y especialistas necesarios, así como la definición de procesos para establecer rutinas controladas y auditables para sentar bases del acceso y uso del PC-CoV19 en el Sistema Nacional de Salud de Venezuela y preparar el diseño y ejecución de estudios clínicos. Se presenta el Protocolo y algunos nudos críticos en su ejecución a la fecha, herramientas y estrategias utilizadas para su solución(AU)

On December 2019, in Wuhan, China, there was an unusual increase in cases of a fast-progressing acute respiratory infection with high fatality rate. Soon after, the causing agent is identiied, a coronavirus called SARS-CoV-2, and a new disease, COVID-19 is characterized. Currently, in the absence of specific, effective and safe treatments, it is justified to explore all scientifically based alternatives available to us, such as the use of Convalescent Plasma (PC-CoV19) as acoadjutant treatment of COVID-19.Plasma from patients who have recovered from an infectious disease, Convalescent Plasma, has been used in the treatment of other infectious disease. There is recent history of its use in diseases caused by another type of coronavirus, and clinical experiences and studies have already been published with preliminary results during this pandemic. Quimbiotec, a Venezuelan State public company that produces blood products and recombinant drugs, and Banco Municipal de Sangre, deined a protocol to promote conditions for aphaeresis, processing, conservation, storage, distribution, transfusion, and evaluation of safety and eficacy of PC-CoV19 as an alternative for the treatment of COVID-19 in Venezuela. This protocol includes identification of capacities, physical structure, equipment and skills, talent, professionals needed, as well as a definition of processes to establish controlled and auditable routines to lay the foundations for access and use of PC-CoV19 in the Venezuela Health System, and prepare the design and implementation of clinical studies. The protocol and currently critical points in its implementation, as well as tools and strategies used for its solution, are presented(AU)

Humanos , Plasma/imunologia , Venezuela , Infecções por Coronavirus/prevenção & controle , Aprovação de Teste para Diagnóstico
San Salvador; MINSAL; jul.1,2020. 36 p. ilus, graf.
Não convencional em Espanhol | LILACS, BISSAL | ID: biblio-1104399


El presente documento reúne los criterios de selección del donante de plasma convaleciente COVID-19 recolección, procesamiento, almacenamiento y distribución para estandarizar a nivel nacional. Y establecer las disposiciones técnicas para la promoción, recolección, procesamiento, almacenamiento y distribución de plasma obtenido de pacientes convalecientes de COVID-19

This document meets the selection criteria for the convalescent plasma donor COVID-19 collection, processing, storage and distribution to standardize at the national level. And establish the technical provisions for the promotion, collection, processing, storage and distribution of plasma obtained from convalescent patients of COVID-19

Plasma , Doadores de Sangue , Infecções por Coronavirus
Nature ; 583(7816): 425-430, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32612231


The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.

Envelhecimento/metabolismo , Envelhecimento/patologia , Barreira Hematoencefálica/metabolismo , Transcitose , Fosfatase Alcalina/metabolismo , Animais , Anticorpos/metabolismo , Transporte Biológico , Proteínas Sanguíneas/administração & dosagem , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/farmacocinética , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Saúde , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasma/metabolismo , Proteoma/administração & dosagem , Proteoma/metabolismo , Proteoma/farmacocinética , Receptores da Transferrina/imunologia , Transcrição Genética , Transferrina/metabolismo
Washington; Organización Panamericana de la Salud; 2020; 20200729. 115 p.
Monografia em Inglês, Espanhol | BIGG | ID: biblio-1116760


Esta guía de práctica clínica provee recomendaciones informadas por la evidencia para la identificación de marcadores y factores de riesgo de mortalidad de los pacientes críticos, control de la infección, recolección de muestras, cuidado de soporte (ventilatorio y hemodinámico), tratamiento farmacológico, rehabilitación temprana, uso de imágenes diagnósticas, prevención de complicaciones y criterios de egreso. Las recomendaciones están dirigidas a todo el personal de salud que atiende a los pacientes en el servicio de urgencias y de emergencias y la unidad de cuidados intensivos (médicos especialistas en medicina de urgencias, neumología, medicina intensiva, medicina interna, anestesiología, infectología, terapistas respiratorios, terapistas físicos, enfermeras y químicos farmacéuticos). La guía está elaborada para su uso por tomadores de decisiones y miembros de entidades gubernamentales relacionados con el manejo de pacientes con COVID-19 en las UCI de la Región de las Américas.

These clinical practice guidelines (short version) were developed in order to provide recommendations for the management of critically ill adult patients with COVID-19 treated in intensive care units (ICUs). These clinical practice guidelines provide evidence-informed recommendations for identifying markers and mortality risk factors in critically ill patients, as well as infection control, sample collection, supportive care (respiratory and hemodynamic), pharmacological treatment, early rehabilitation, diagnostic imaging use, prevention of complications, and discharge requirements. The recommendations are for all healthcare staff who deal with patients in emergency departments and ICUs. These guidelines are also intended for use by decision-makers and government entities involved in the management of patients with COVID-19 in ICUs in the Region of the Americas. This document is the result of a rapid guideline adaptation process. The information presented reflects published evidence as of the date of inclusion in the document. The recommendations are based on the evidence available and the quality thereof (GRADE methodology) at the time the guidelines were published. However, PAHO recognizes that there are numerous research projects under way and will periodically update these reviews and the applicable recommendations.

Humanos , Adulto , Antivirais/uso terapêutico , Plasma/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Administração dos Cuidados ao Paciente/organização & administração , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Assistência Centrada no Paciente/organização & administração , Prática Clínica Baseada em Evidências/organização & administração , Gravidade do Paciente , Betacoronavirus , Fatores Imunológicos/uso terapêutico , Unidades de Terapia Intensiva/organização & administração , Antibacterianos/uso terapêutico , América/epidemiologia
Arthritis Res Ther ; 22(1): 125, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: covidwho-457521


BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. METHODS: A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. RESULTS: The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. CONCLUSIONS: A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.

Betacoronavirus , Infecções por Coronavirus , Monitoramento de Medicamentos/normas , Hidroxicloroquina/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pandemias , Pneumonia Viral , Adulto , Idoso , Cromatografia Líquida/métodos , Cromatografia Líquida/normas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Espectrometria de Massas/métodos , Espectrometria de Massas/normas , Pessoa de Meia-Idade , Plasma , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Soro , Adulto Jovem
BMJ Open ; 10(6): e039978, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: covidwho-592392


OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments.

Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Antivirais/farmacologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus , Imunização Passiva/métodos , Imunossupressores/farmacologia , Pandemias , Plasma/imunologia , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto/classificação , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Ensaios Clínicos como Assunto/estatística & dados numéricos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estudos Transversais , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Sistema de Registros/estatística & dados numéricos , Terapias em Estudo/métodos , Terapias em Estudo/estatística & dados numéricos