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The COVID-19 pandemic has driven the search for alternative therapies, including convalescent plasma, historically used in infectious diseases. Despite results in other diseases, its effectiveness against COVID-19 remains uncertain with conflicting results in clinical trials. A pragmatic, single-center, prospective, and open randomized controlled trial was carried out in a hospital in Brazil, with the aim of evaluating the impact of convalescent plasma on the clinical improvement of patients hospitalized with COVID-19. The World Health Organization (WHO) ordinal scale was used to measure clinical improvement, focusing on the reduction in disease severity by up to 2 points, while antibody and C-reactive protein levels were monitored over time. After hospital admission, participants were randomized 1:1 to receive convalescent plasma and standard treatment or to be part of the control group with standard treatment. Follow-up was carried out on days 1, 3, 7, 14 and/or at discharge. From January 14 to April 4, 2022, 38 patients were included, but 3 were excluded due to protocol deviations, resulting in a total of 35 patients: 19 in the control group and 16 in the plasma group. There was no significant difference in clinical improvement between the convalescent plasma group and the control group, nor in secondary outcomes. The study had limitations due to the small number of patients and limited representation of COVID-19 cases. Broader investigations are needed to integrate therapies into medical protocols, both for COVID-19 and other diseases. Conducting randomized studies is challenging due to the complexity of medical conditions and the variety of treatments available.
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Background: The use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of COVID-19. This study evaluated the safety and efficacy of the use of donor CP for COVID-19. Material and methods: A double-blind, randomized controlled clinical trial was conducted from May to October 2020. Thirty-nine participants with moderate (II) and severe (III) stages of COVID-19 confirmed by RT-PCR were included. The study randomization rate was set at 3:1. CPs were chosen for application with a neutralizing antibody titer of ≥1:32. Results: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 (95.0% CI [0.07−0.45, p < 0.001]) in the group receiving CP compared with the control group; protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher (512 (32−16,384) vs. 96 (32−256), p = 0.01); the PAO2/FIO2 index showed a significant improvement in the group receiving CP (251.01 (109.4) vs. 109.2 (62.4), p < 0.001, in the control group). Conclusion: CP is safe and effective, as it decreased mortality in the CP group compared with the control group.
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Abstract Introduction As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates. Method We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender. Results In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies. Conclusion These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Infecções por Coronavirus , Teste Sorológico para COVID-19 , COVID-19 , Plasma , Doadores de Sangue , SARS-CoV-2RESUMO
INTRODUCTION: As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates. METHOD: We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender. RESULTS: In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies. CONCLUSION: These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms.
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Resumen La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO /FiO, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.
Abstract The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO / FiO , ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Pandemias , COVID-19/terapia , Plasma , Imunização Passiva , SARS-CoV-2RESUMO
Resumen Cada vez sabemos más sobre este enemigo mortal de la familia de los Betacoronavirus, llamado inicialmente 19-nCoV, causante de la COVID-19 (Coronavirus infectous disease por su sigla en inglés), hoy clasificado SARS-CoV-2, porque es responsable de producir el SARS (síndrome respiratorio agudo severo, por sus siglas en inglés) y que comparte una fuerte homología de secuencia con el SARS-CoV, su primo hermano causante de la epidemia en 2003 del SARS, ambos capaces de diseminarse rápidamente, en particular este, y causar un gran caos mundial como ha sucedido con esta pandemia. Con base en estudios previos de focalización en el SARS-CoV, y también en el virus causante del MERS (síndrome respiratorio del Oriente Medio, por sus siglas en inglés), y con el conocimiento que se tiene actualmente sobre el SARS-CoV-2, se exploran en este artículo algunas opciones terapéuticas para el manejo de la infección por este virus complejo y con capacidad letal, mencionando algunos aspectos de relevancia patogénica. Se enfatizó en las posibles alternativas de manejo desde la fisiopatología y patogénesis hasta la evidencia actualmente disponible. Exploraremos el uso probable de ECA2 recombinante, algunas moléculas experimentales, revisaremos los antimaláricos (cloroquina e hidroxicloroquina), esteroides, azitromicina, antivirales específicos como remdesivir, lopinavir/ritonavir, biológicos como tocilizumab, anticuerpos monoclonales antivirales, y haremos énfasis en la trasfusión de plasma de convalecientes desde el principio de inmunización pasiva, de gran utilidad.
Abstract We know more and more about this deadly enemy of the Betacoronavirus family, initially called 19- nCoV that causes COVID-19 (Coronavirus infectous disease), today classified SARS-CoV-2, because it is responsible for producing SARS (severe acute respiratory syndrome), It shares a strong sequence homology with SARS-CoV, its cousin that caused the 2003 SARS epidemic, both capable of spreading rapidly, particularly this one and causing great global chaos as has happened with this pandemic. Based on previous studies targeting SARS-CoV, and also on the virus that causes MERS (Middle East Respiratory Syndrome); and with the current knowledge about SARS-CoV-2, we will explore some therapeutic options for the management of infection by this complex and lethal virus, mentioning some aspects of pathogenic relevance. Possible management alternatives from the pathophysiology and pathogenesis to the evidence currently available were emphasized. We will explore the probable use of ECA2 recombinate, some experimental molecules, we will review some of the antimalarials (chloroquine and hydroxychloroquine), steroids, azithromycin, specific antivirals such as remdesivir, lopinavir / ritonavir, biologics such as tocilizumab, monoclonal antiviral antibodies, and we will emphasize transfusion of convalescent plasma from the passive immunization principle, very useful.
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Humanos , Masculino , Feminino , Terapêutica , COVID-19 , Antivirais , Vacinas , Cloroquina , Imunização Passiva , Colômbia , Pandemias , Glicoproteína da Espícula de CoronavírusRESUMO
The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO2 / FiO2, ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.
La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO2/FiO2, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.