Revisão de literatura sobre os aspectos fisiológicos e nutricionais em bezerros alimentados com colostro acidificado / Literature review on physiological and nutritional aspects in calves fed acidified colostrum / Revisión de la literatura sobre aspectos fisiológicos y nutricionales en terneros alimentados con calostro acidificado

A colostragem é essencial para a saúde dos bezerros neonatos, uma vez que não há a transferência de imunidade através da placenta, ou seja, o contato inicial do organismo com anticorpos se dá através da primeira mamada, onde há transferência da imunidade passiva. Sendo assim, o objetivo do trabalho é revisar os benefícios da acidificação ou silagem do colostro para otimizar a conservação da dieta líquida em fazendas; analisar o impacto no desempenho de bezerros em comparação com o colostro tradicional refrigerado em aleitamentos convencionais. O volume ideal preconizado é, no mínimo, 10% do peso vivo do animal nas primeiras duas horas e mais 5% do peso vivo nas seis a oito horas seguintes a primeira ingestão, para que se obtenha um bom desenvolvimento durante o crescimento, caso contrário, a falta da administração do colostro nas primeiras horas de vida predispõe enfermidades, tais como pneumonia e diarreia, prejudicando assim a saúde e consequentemente o desempenho em relação a outros animais que receberam uma colostragem adequada. Problemas com a qualidade do colostro surgem devido ao armazenamento inadequado, especialmente em propriedades sem refrigeração. A falta de sistemas de congelamento resulta em administração de leite em temperatura ambiente por períodos prolongados, prejudicando assim a imunidade e nutrição dos bezerros durante a colostragem. Todavia, há alternativas para o problema tal como o fornecimento de silagem de colostro. Em alguns casos, o processo de acidificação demanda a adição de ácidos no leite, a fim de evitar o crescimento de microrganismos patogênicos. O principal aspecto positivo do leite acidificado é a manutenção em temperatura ambiente, ou seja, não há a necessidade de passar por processos de refrigeração.

Colostrum is essential for the health of newborn calves, since there is no transfer of immunity through the placenta, that is, the body's initial contact with antibodies occurs through the first feeding, where there is a transfer of passive immunity. Therefore, the objective of the work is to review the benefits of acidifying or colostrum silage to optimize the conservation of liquid diets on farms; analyze the impact on calf performance compared to traditional refrigerated colostrum in conventional sucklers. The recommended ideal volume is at least 10% of the animal's live weight in the first two hours and a further 5% of its live weight in the six to eight hours following the first ingestion, so that good development is achieved during growth, otherwise, the lack of colostrum administration in the first hours of life predisposes diseases, such as pneumonia and diarrhea, thus harming health and consequently performance in relation to other animals that received adequate colostrum. Problems with colostrum quality arise due to inadequate storage, especially in unrefrigerated properties. The lack of freezing systems results in milk being administered at room temperature for prolonged periods, thus damaging the calves immunity and nutrition during colostrum. However, there are alternatives to the problem such as the supply of colostrum silage. In some cases, the acidification process requires the addition of acids to the milk in order to prevent the growth of pathogenic microorganisms. The main positive aspect of acidified milk is that it remains at room temperature, that is, there is no need to undergo refrigeration processes.

El calostro es esencial para la salud de los terneros recién nacidos, ya que no existe transferencia de inmunidad a través de la placenta, es decir, el contacto inicial del cuerpo con los anticuerpos ocurre a través de la primera alimentación, donde existe una transferencia de inmunidad pasiva. Por lo tanto, el objetivo del trabajo es revisar los beneficios de acidificar o ensilar el calostro para optimizar la conservación de dietas líquidas en granjas; analizar el impacto en el rendimiento de los terneros en comparación con el calostro refrigerado tradicional en lechones convencionales. El volumen ideal recomendado es al menos el 10% del peso vivo del animal en las dos primeras horas y otro 5% de su peso vivo en las seis a ocho horas siguientes a la primera ingesta, para que se consiga un buen desarrollo durante el crecimiento, en caso contrario. la falta de administración de calostro en las primeras horas de vida predispone a enfermedades, como neumonía y diarrea, perjudicando la salud y consecuentemente el rendimiento en relación a otros animales que recibieron el calostro adecuado. Los problemas con la calidad del calostro surgen debido a un almacenamiento inadecuado, especialmente en propiedades no refrigeradas. La falta de sistemas de congelación provoca que la leche se administre a temperatura ambiente durante períodos prolongados, dañando así la inmunidad y la nutrición de los terneros durante el calostro. Sin embargo, existen alternativas al problema como el suministro de ensilaje de calostro. En algunos casos, el proceso de acidificación requiere la adición de ácidos a la leche para evitar el crecimiento de microorganismos patógenos. El principal aspecto positivo de la leche acidificada es que se mantiene a temperatura ambiente, es decir, no es necesario someterse a procesos de refrigeración.

Uso de plasma de convalecientes de COVID-19 en pacientes hospitalizados por SARS-CoV-2 de moderada grave-dad en la Región de Los Ríos, Chile / Assessing Convalescent Plasma Efficacy in Moderate COVID-19 Hospitalizations: A Bicentric Retrospective Study

INTRODUCCIÓN: COVID-19 cobró millones de vidas especialmente en la era pre-vacunas. Estudios preliminares mostraban eficacia promisoria del plasma de personas convalecientes anti SARS-CoV-2 (PPC). Objetivo: evaluar la eficacia del PPC en hospitalizados por COVID-19 de moderada gravedad. MATERIAL Y MÉTODOS: Estudio retrospectivo, bicéntrico, en adultos hospitalizados por COVID-19 moderado (no crítico) que requirieron oxigenoterapia. Al plasma donado por sobrevivientes de cuadros leves (600 cc) se les realizó búsqueda de IgG anti SARS-CoV-2. Se evaluó su impacto en mortalidad, estadía hospitalaria (días) y necesidad de ventilación mecánica (VMI). RESULTADOS: De los 119 pacientes incluidos, 58% eran hombres (edad mediana 60 años), 88% poseía comorbilidad y 43% tenía "CALL score" de alto riesgo. 43 pacientes (36%) recibieron PPC, sólo 15 (12,6%) precozmente (< 7 días). 22 pacientes debieron trasladarse a unidad intensiva, 18 recibieron VMI y 15 fallecieron (12,6%). El uso de PPC no se asoció a cambios en la mortalidad (p = 0,16), necesidad de VMI (p = 0,79) ni en la estadía hospitalaria (p = 0,24). Su administración en forma precoz (< 7 días de síntomas) tampoco demostró asociación significativa. La presencia de cardiopatía y el requerir posteriormente VMI fueron factores independientes asociados a mortalidad. CONCLUSIONES: El uso de PPC en pacientes hospitalizados por COVID-19 de moderada gravedad no se asoció a menor mortalidad, estadía hospitalaria ni necesidad de VMI.

INTRODUCTION: COVID-19 claimed millions of lives, mainly in the pre-vaccine era. Preliminary studies showed promising efficacy of convalescent plasma against SARS-CoV-2 (CP). Objective: To evaluate the efficacy of CP in patients hospitalized for COVID-19 with moderate severity. METHODS: Retrospective, bicentric study including adults hospitalized for moderate (non-critical) COVID-19 who required oxygen therapy. CP donated by survivors of mild cases (600 cc) were searched for IgG anti-SARS-CoV-2. Its impact on mortality, hospital stay (days), and need for mechanical ventilation (IMV) was evaluated. RESULTS: Of the 119 patients included, 58% were men (median age 60 years), 88% had comorbidity, and 43% had a high-risk CALL score. Forty-three patients (36%) received CP, only 15 (12.6%) early (< 7 days). Twenty-two patients had to be transferred to the intensive care unit; 18 received IMV, and 15 died (12.6%). The use of CP was not associated with changes in mortality (p = 0.16), need for IMV (p = 0.79), or hospital stay (p = 0.24). Its early administration (< 7 days of symptoms) did not show a significant association either. The presence of heart disease and subsequently requiring IMV were independent factors of mortality. CONCLUSIONS: The use of CP in patients hospitalized for moderately severe COVID-19 was not associated with lower mortality, hospital stay, or the need for IMV.

Animais peçonhentos e sua trajetória secular para as ações de saúde: do histórico à aplicação / Venomous animals and their secular trajectory for health actions: from history to application / Los animales venenosos y su trayectoria secular para las acciones de salud: de la historia a la aplicación

O livro Os animais peçonhentos na saúde pública expõe um vasto histórico de acidentes envolvendo problemas de saúde provocados por animais peçonhentos. Os autores resgatam trabalhos e vivências, descritos por Louis Pasteur e Vital Brazil, fundamentais para o desenvolvimento de processos da ciência translacional como compreendida hoje, no século XXI. A obra é marcada pela defesa da necessidade de políticas públicas coerentes que sejam capazes de promover ações de capacitação, prevenção, diagnóstico, tratamento e reabilitação dos pacientes.

The book Os animais peçonhentos na saúde pública presents a vast history of accidents involving health problems caused by venomous animals. The authors rescue works and experiences, described by Louis Pasteur and Vital Brazil, fundamental for the development of translational science processes as understood today, in the 21st century. The work is marked by the defense of the need for coherent public policies capable of promoting training, prevention, diagnosis, treatment and rehabilitation of patients.

El libro Os animais peçonhentos na saúde pública expone una vasta historia de accidentes que involucran problemas de salud causados por animals venenosos. Los autores rescatan obras y experiencias, descritas por Louis Pasteur y Vital Brazil, fundamentales para el desarrollo de los procesos de ciencia translacional tal como se entienden hoy, en el siglo XXI. El libro está marcado por la defensa de la necesidad de políticas públicas coherentes capaces de promover la formación, la prevención, el diagnóstico, el tratamiento y la rehabilitación de los pacientes.

Therapeutics and COVID-19: living guideline - 16 September 2022

The WHO Therapeutics and COVID-19: living guideline contains the Organization's most up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. This twelfth version of the WHO living guideline now contains 19 recommendations. This latest update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers and Janus kinase (JAK) inhibitors in patients with severe or critical COVID-19, and modifies previous recommendations for the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe COVID-19.

Manejo clínico y diagnóstico para pacientes con enfermedades de inmunodeficiencia primaria por déficit de producción de anticuerpos / Clinical management and diagnosis for patients with primary immunodeficiency diseases due to deficiency of antibody production

1. INTRODUCCIÓNLas inmunodeficiencias primarias son un grupo de más de 400 enfermedades, en las cuales el sistema inmune pierde sus funciones de reconocimiento de patógenos o funciona de forma inapropiada. Algunas de ellas son relativamente comunes; mientras otras son raras. Estas enfermedades son en ocasiones de por vida, debilitantes y costosas1,2.Sin embargo, muchos progresos se han hecho desde su des-cripción original en el año de 1952. Se han dado grandes pasos en cuanto a su entendimiento de las Inmunodeficiencias Pri-marias a nivel genético, de sus características, y tratamiento. Algunos tipos afectan un único tipo de célula; otros afectan más de un componente del sistema inmune2,3.Tomando en cuenta que la aproximación es entre 1-2% de la población, a nivel país se puede decir que un aproximado entre 170 000 a 340 000 pacientes en el país no cuentan con un diagnóstico y muchos mueren por falta de este. El número de afiliados al Instituto Ecuatoriano de Seguridad Social hasta julio de 2021 es de 3 672,611 por lo que se considera que un estimado de 36 726 a 73 452 pacientes podrían presentar este tipo de enfermedades y requerir de atención por infecciones a repetición, enfermedad autoinmune y enfermedades linfopro-liferativas, además de que sin un tratamiento específico po-drían fallecer debido a infecciones graves o tener discapacidad permanente, lo que implica mayor carga para el sistema de Seguridad Social en subsidios y menores ingresos. Ecuador, cuenta con 86 pacientes diagnosticados, según la base de datos de la Sociedad Latino-Americana de Inmunodeficiencias4.Algunas terapias, como la de reemplazo para inmunoglobu-linas, a la que es tributaria más del 60% de estas patologías permite que la esperanza de vida y la morbilidad casi alcancen a aquellos que no presentan la enfermedad5­7.

1. INTRODUCTIONPrimary immunodeficiencies are a group of more than 400 diseases, in which the immune system loses its pathogen recog-nition functions or functions inappropriately. Some of them are relatively common, while others are rare. These diseases are sometimes lifelong, debilitating, and costly1,2. However, much progress has been made since its original description in 1952. Great strides have been made in understanding Primary Immunodeficiencies at the genetic level, their characteristics, and treatment. Some types affect only one type of cell; others affect more than one component of the immune system2,3. Considering that the approximation is between 1 to 2% of the population, at the country level we could say that approximately between 170 000 to 340 000 patients in the country do not have a diagnosis and many die due to lack of it. The number of social security affiliates until July 2021 is 3 672,611, so we could consider that approximately 36 726 to 73 452 patients could present this type of disease and require care for recurrent infections, autoimmune disease and lymphoproliferative diseases, in addition to the fact that without specific treatment they could die due to serious infections or have permanent disability, which implies a greater burden for the social security system in subsidies and lower income. Currently the country has 86 diagnosed patients, according to the database of the Latin American Society of Immunodeficiencies4. Many of the therapies, such as immunoglobulin replacement therapy, to which more than 60% of these pathologies are de-pendent, allow life expectancy and morbidity to almost reach those who do not have the disease 5­7.

Development and implementation of a COVID-19 convalescent plasma program in a middle-income economy

Abstract Introduction Convalescent Plasma therapy is one of the therapeutic strategies that has been used for patients with the Covid-19 disease. Implementing a program with national extension to supply hospitals with this blood component is a great challenge mainly in a middle-income economy. Objectives Our objective was to develop and implement a Covid-19 Convalescent Plasma Program which met established quality standards and was adapted to a reality of limited resources. Methods A multicentric convalescent plasma collection program was developed and implemented, based on four main sequential procedures: selective donor recruitment, pre-donation antibody screening (Anti-SARS-CoV-2- Chemiluminescence IgG Abbott), convalescent plasma collection by apheresis or whole-blood processing and distribution to the hospitals according to local demand. Results From the 572 candidates submitted to the pre-donation antibody screening, only 270 (47%) were considered eligible for plasma donation according to the established criteria. Higher levels of total antibody were associated with the donor age being above 45 years old (p= 0.002), hospital admission (p= 0.018), and a shorter interval between the diagnosis of the SARS-CoV-2 infection and plasma donation (p < 0.001). There was no association between the ABO and Rh blood groups and their antibody levels. Of the 468 donations made, 61% were from the collection of whole-blood and 39%, from apheresis. The Covid-19 Convalescent Plasma units obtained were distributed to 21 different cities throughout the country by air or ground transportation. Conclusion The implementation of a Covid-19 Convalescent Plasma program in a continental country with relatively scarce resources is feasible with alternative strategies to promote lower cost procedures, while complying with local regulations and meeting quality standards.

Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19: Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia / Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia

Há diversas terapias sendo utilizadas ou propostas para a COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é elaborar recomendações para subsidiar decisões sobre o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: Um grupo de 27 membros, formado por especialistas, representantes do Ministério da Saúde e metodologistas, integra essa diretriz. Foi utilizado o método de elaboração de diretrizes rápidas, tomando por base a adoção e/ou a adaptação de recomendações a partir de diretrizes internacionais existentes (GRADE ADOLOPMENT), apoiadas pela plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Foram geradas 16 recomendações. Entre elas, estão recomendações fortes para o uso de corticosteroides em pacientes em uso de oxigênio suplementar, para o uso de anticoagulantes em doses de profilaxia para tromboembolismo e para não uso de antibacterianos nos pacientes sem suspeita de infecção bacteriana. Não foi possível fazer uma recomendação quanto à utilização do tocilizumabe em pacientes hospitalizados com COVID-19 em uso de oxigênio, pelas incertezas na disponibilidade e de acesso ao medicamento. Foi feita recomendação para não usar azitromicina, casirivimabe + imdevimabe, cloroquina, colchicina, hidroxicloroquina, ivermectina, lopinavir/ ritonavir, plasma convalescente e rendesivir. Conclusão: Até o momento, poucas terapias se provaram efetivas no tratamento do paciente hospitalizado com COVID-19, sendo recomendados apenas corticosteroides e profilaxia para tromboembolismo. Diversos medicamentos foram considerados ineficazes, devendo ser descartados, de forma a oferecer o melhor tratamento pelos princípios da medicina baseada em evidências e promover economia de recursos não eficazes.

Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19

ABSTRACT BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

Uso de plasma convalescente no tratamento da COVID-19: protocolo de revisão sistemática / Use of convalescent plasma in the treatment of COVID-19: a systematic review protocol / Uso de plasma convaleciente en el tratamiento de COVID-19: protocolo de revisión sistemática

OBJETIVO: analisar a efetividade terapêutica do plasma convalescente utilizado em pacientes com confirmação de diagnóstico de COVID-19. MÉTODO: revisão sistemática para avaliação tecnológica em saúde para responder à pergunta PICO: O plasma convalescente é efetivo na redução da carga viral de pacientes com diagnóstico SARS-CoV-2 (COVID-19) quando comparado ao não uso do plasma? Foi realizada uma busca sistemática nas bases de dados Pubmed/Medline, BVS, Embase, CINAHL, LILACS, Cochrane e Google Scholar. A triagem inicial dos títulos e resumos será avaliada de forma independente por dois revisores. Para avaliação do risco de viés de revisões sistemáticas será utilizado o AMSTAR-2; já para avaliação da qualidade da evidência será aplicado o GRADE.

OBJECTIVE: to analyze the therapeutic effectiveness of convalescent plasma used in patients with confirmed COVID-19 diagnosis. METHOD: systematic review for health technology assessment to answer the PICO question: Is convalescent plasma effective in reducing the viral load of patients diagnosed with SARS-CoV-2 (COVID-19) when compared to not using plasma? A systematic search was performed in Pubmed/Medline, BVS, Embase, CINAHL, LILACS, Cochrane and Google Scholar databases. The initial screening of titles and abstracts will be independently assessed by two reviewers. To assess the risk of bias in systematic reviews, AMSTAR-2 will be used,and to assess the quality of evidence, GRADE will be used.

OBJETIVO: analizar la efectividad terapéutica del plasma convaleciente utilizado en pacientes con confirmación de diagnóstico de COVID-19. MÉTODO: revisión sistemática para evaluación tecnológica en salud para responder a la pregunta PICO ¿Es el plasma convaleciente efetivo en la reducción de la carga viral de pacientes con diagnóstico SARS-CoV-2(COVID-19) cuando se la compara a la no utilización del plasma Se realizó una búsqueda sistemática en las bases de datos Pubmed/Medline, BVS, Embase, CINAHL,L ILACS, Cochrane y Google Scholar. La selección inicial de los títulos y resúmenes serán evaluados de forma independiente por dos revisores. Para evaluación del riesgo de sesgo de revisiones sistemáticas se utilizará el AMSTAR-2, mas para evaluación de la calidad de la evidencia será aplicado el GRADE.

The use of convalescent plasma therapy in the management of a pregnant woman with COVID-19: a case report

ABSTRACT The coronavirus disease 19 (COVID-19) is responsible for the current worldwide pandemic. Treatment and prophylaxis are still under investigation. Convalescent plasma therapy could be an alternative. We report a case of a 41-year-old patient, at 28 weeks of gestation, was hospitalized with COVID-19. On the 10th day after onset of symptoms, the clinical picture worsened, and she required high-flow oxygen therapy (30L/minute), with 92% oxygen saturation, and chest X-ray showing mild bilateral opacities at lung bases. Blood tests showed D-dimer 1,004ng/mL, C-reactive protein 81mg/L, pro-calcitonin 0.05ng/mL and interleukine-6 42.9pg/mL. The therapy chosen was Tazocin® 12g/day, vancomycin 2g/day, and methylprednisolone 40mg/day. In addition, convalescent plasma therapy was administered (275mL) uneventfully, including SARS-CoV-2 antibodies and neutralizing antibodies >1:160. The patient had a fast recovery. The early administration of convalescent plasma, with high titers of neutralizing antibodies, may be an alternative option for severe COVID-19 during pregnancy, until further studies demonstrate an efficient and safe treatment or prophylaxis.

Infección por SARS-COV-2 en pacientes con neoplasias hematológicas y trasplantes / SARS-COV-2 infection in patients with hematological malignancies and transplants

Resumen La infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes de células progenitoras hematopoyéticas (TCPH) puede ser grave y con importante mortalidad. Llevamos a cabo un estudio prospectivo y observacional que tuvo como objetivo describir las características clínicas, epide miológicas y la evolución de la infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y TCPH. Se incluyeron 20 pacientes adultos con una mediana de edad de 58 años y una mediana de score de Charlson de 3. Las infecciones fueron de adquisición comunitaria y nosocomial en el 60% y 40% respectivamente, y el 30% de los pacientes tenía antecedente de contacto con una persona infectada por SARS-CoV-2. El 65% pre sentó infiltrados pulmonares, mayormente con patrón de vidrio esmerilado en la tomografía computarizada de tórax. Casi la mitad de los pacientes tuvo enfermedad grave y crítica, y una alta proporción recibió plasma de convalecientes como tratamiento. Presentaron complicaciones e infecciones hospitalarias el 20% y 15% respec tivamente, y tuvieron una mediana de días de internación prolongada. La mortalidad a 30 días fue del 10%. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico.

Abstract. SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.

Inmunoterapia pasiva con anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19 / Passive immunotherapy with equine polyclonal antibodies (hyperimmune equine serum) for the treatment of patients with COVID-19

INTRODUCIÓN: El presente informe es producto del trabajo colaborativo de la Comisión Nacional de Evaluación de Tecnologías de Salud (CONETEC), dependiente del Ministerio de Salud de la Nación y creada por RM N° 623/2018. La CONETEC realiza evaluaciones y emite recomendaciones a la autoridad sanitaria sobre la incorporación, forma de uso, financiamiento y políticas de cobertura de las tecnologías sanitarias desde una perspectiva global del sistema de salud argentino. En sus evaluaciones y recomendaciones, la CONETEC tiene en cuenta criterios de calidad, seguridad, efectividad, eficiencia y equidad, evaluados bajo dimensiones éticas, médicas, económicas y sociales. Sus resultados son consensuados mediante discusiones públicas y ponderados a través de un marco de valor explícito, con la participación de todos los actores involucrados en el proceso de toma de decisiones en salud. Los informes y recomendaciones de esta comisión surgen de este proceso público, transparente y colaborativo, siendo de libre consulta y acceso para toda la sociedad. El objetivo del presente informe es evaluar parámetros de eficacia, seguridad y conveniencia de anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19. OBJETIVO El objetivo del presente informe es evaluar parámetros de eficacia, seguridad y conveniencia de anticuerpos policlonales equinos (suero equino hiperinmune) para el tratamiento de pacientes con COVID-19. METODOLOGÍA: Realizamos una evaluación "viva" (con un proceso de actualización continua) de una tecnología sanitaria, basada en evidencia proveniente de revisiones sistemáticas "vivas" de referencia y guías de práctica clínica de alta calidad metodológica para brindar parámetros actualizados y balanceados que sean de utilidad para la toma de decisiones en los diferentes niveles de gestión. RESULTADOS: Se identificó una revisión sistemática que cumple con los criterios de inclusión del presente informe. Adicionalmente se identificaron otras dos revisiones sistemáticas con adecuado proceso de desarrollo pero ninguna contestó la pregunta pertinente al presente informe. La revisión sistemática identificada incluyó un estudio aleatorizado con un total de 243 pacientes aleatorizados a suero equino hiperinmune o placebo. Se realizaron múltiples análisis de subgrupo incluyendo uno que comparó pacientes según su severidad al comienzo del estudio. Ninguno de estos análisis mostró resultados que sugieran un efecto diferencial en los subgrupos comparados. CONCLUSIONES: El cuerpo de evidencia disponible hasta el momento muestra que existe incertidumbre en el efecto de los anticuerpos policlonales equinos (suero equino hiperinmune) sobre la mortalidad y el ingreso en ventilación mecánica. El uso de anticuerpos policlonales equinos (suero equino hiperinmune) podría impactar positivamente en el tiempo de mejoría clínica, pero podría no incrementar la proporción de pacientes que alcanzan la recuperación clínica que lleva al alta hospitalaria. Los anticuerpos policlonales equinos (suero equino hiperinmune) podrían no asociarse a afectos adversos severos. La incertidumbre sobre el efecto de la tecnología evaluada sobre los desenlaces críticos para pacientes hospitalizados con COVI-19 (mortalidad y requerimiento de ventilación invasiva) determina que la certeza en los efectos de suero equino sobre la salud de pacientes con COVID-19 sea muy baja. A pesar que la tecnología se produce en Argentina lo que facilitaría su acceso, encontramos barreras relacionadas con una amplia población objetivo y elevado costo comparativo de esta intervención que podrían acarrear problemas de producción y afectar la distribución equitativa en situaciones de alta demanda. No identificamos recomendaciones con el rigor metodológico apropiado para ser incluidas en el informe.

El plasma de convalecientes como un tratamiento potencial en pacientes con COVID-19 / Convalescent plasma as potential treatment for COVID-19 patients

Introducción: El plasma de convalecientes es una inmunoterapia pasiva que se ha usado para el tratamiento y prevención de muchas enfermedades infecciosas por más de un siglo. Dada la falta de tratamiento específico para el nuevo coronavirus SARS-CoV-2, el plasma de convalecientes es una alternativa terapéutica potencial contra la COVID-19. Objetivo: Realizar una revisión del empleo del plasma de convalecientes como alternativa terapéutica a la COVID-19. Desarrollo: Se empleó la estrategia de búsqueda del tema; consultando las bases de datos Pubmed, SciELO, Lilacs, Cochrane Library y Web of Science. El plasma de convalecientes ha mostrado efectividad en el tratamiento de varias enfermedades virales. Así, la evidencia sobre su uso en los pacientes con COVID-19 es escasa, aunque se han obtenido resultados alentadores, pero no concluyentes por falta de un número mayor ensayos clínicos. Al mismo tiempo, Cuba incluye en sus protocolos de actuación contra la COVID-19 este tratamiento. Conclusiones: Esta alternativa resulta una herramienta inmunoterapéutica en los pacientes con la COVID-19, ya que mejora el estado clínico y disminuir la tasa de letalidad. Sin embargo, se necesitan más ensayos clínicos controlados y aleatorizados que afirmen su efectividad y seguridad(AU)

Introduction: Convalescent plasma is a form of passive immunotherapy which has been used for the treatment and prevention of many infectious diseases for more than one century. Given the absence of a specific treatment for the novel coronavirus SARS-CoV-2, convalescent plasma is a potential therapeutic alternative against COVID-19. Objective: Carry out a review about the use of convalescent plasma as a therapeutic alternative against COVID-19. Discussion: A search was conducted about the topic in the databases Pubmed, SciELO, Lilacs, Cochrane Library and Web of Science. Convalescent plasma has been shown to be effective in the treatment of several viral diseases. However, evidence of its use in COVID-19 patients is scant. Promising results have been obtained, though, but they are not conclusive due to the need of a larger number of clinical trials. In Cuba this treatment is included among the clinical management protocols for COVID-19. Conclusions: This alternative is an immunotherapeutic tool for the treatment of COVID-19 patients, since it improves their clinical status and reduces lethality rates. However, more controlled and randomized clinical trials are required confirming its effectiveness and safety(AU)

Tratamiento con Suero Equino Hiperinmune en pacientes con COVID-19 / Treatment with Hyperimmune Equine Serum in patients with COVID-19

INTRODUCCIÓN: El 30 de enero la Organización Mundial de la Salud (OMS) declaró el brote de Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) en China Emergencia de Salud Pública de Importancia Internacional. No existen aún tratamientos específicos para prevenir o curar la enfermedad. La dexametasona ha demostrado reducir la mortalidad en pacientes con neumonía por Coronavirus Disease 2019 (COVID-19), y el tratamiento de soporte resulta fundamental según la necesidad de cada caso (oxigeno, ventilación no invasiva, ventilación invasiva, tratamiento de las complicaciones, etc.). La estrategia de vacunación comenzó recientemente en nuestro país pero su impacto no podrá evaluarse/medirse inmediatamente. En este contexto, se desarrollaron sueros equinos hiperinmunes (SEH) específicos para el tratamiento de COVID-19 utilizando el dominio de unión al receptor (RBD) de la proteína Spike del SARS-CoV-2 como inmunógeno. OBJETIVO: Realizar un informe ultra-rápido de evaluación de tecnología sanitaria sobre suero equino hiperinmune en tratamiento de pacientes con COVID-19. METODOLOGÍA: Un equipo multidisciplinario, independiente de conflictos de interés con la tecnología, realizó una búsqueda exhaustiva y sistemática de la literatura científica. Los puntos finales analizados fueron relacionados a la eficacia, la seguridad, el impacto económico, en la equidad y en el sistema de salud. RESULTADOS: En el registro de estudios ClinicalTrials.gov se encontraron publicados: un protocolo que aún se encuentra en la etapa previa al reclutamiento de pacientes, conducido en Costa Rica, un estudio similar en la misma fase de desarrollo llevado a cabo en México y un tercer protocolo registrado en ClinicalTrials.gov desarrollado en Argentina. A la fecha no se han publicado en dicho sitio los resultados del estudio. Se obtuvo información del preprint de la publicación del ensayo destinada a una revista internacional. El diseño se presenta como un ensayo clínico aleatorizado (ECA). Se incluyeron 242 pacientes con diagnóstico confirmado de SARS-CoV-2 por técnica de reacción en cadena de la polimerasa (PCR) con manifestaciones clínicas moderadas y/o graves, que fueron aleatorizados a recibir solución de SEH. No se encontraron diferencias estadísticamente significativas en el impacto en la mortalidad, ni en el tiempo de hospitalización, ni en el requerimiento de unidad de terapia intensiva (UTI), ni en la mejoría clínica de los pacientes tratados con SEH vs tratamiento estándar. CONCLUSIÓN: Existe incertidumbre en la eficacia de las inmunoglobulinas equinas en pacientes hospitalizados con infección por SARS-CoV-2, ya que la certeza global de la evidencia es muy baja. La aprobación de esta tecnología por parte de la Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) se realizó en el Marco de Registros Especiales en el contexto de enfermedad pandémica seria, para la cual no existen aún otros tratamientos efectivos. El impacto económico potencial en los sistemas de salud puede ser elevado y distraer recursos limitados necesarios para hacer frente a la pandemia con tecnologías que al momento han demostrado cierta eficacia y seguridad. Esto es aún más relevante en el contexto de crisis económica que nuestro enfrentan los países como consecuencia de la situación sanitaria provocada por la pandemia. El impacto en la equidad puede ser perjudicial y el impacto en las organizaciones del sistema de salud y potenciales judicializaciones, a partir de las recomendaciones emitidas, puede ser perjudicial para lograr resultados eficientes y equitativos en la salud de la población. En este contexto, el balance beneficio/costo no es favorable y son necesarios estudios con mayor cantidad de pacientes para definir la eficacia clínica, la seguridad, el grado de recomendación y los subgrupos más beneficiados para elección del tratamiento en forma oportuna. La presente evaluación ha consistido en una evaluación sanitaria de los datos existentes. Finalmente, como ha manifestado la Organización Panamericana de la Salud (OPS), en el marco de las recomendaciones sobre intervenciones no probadas para la pandemia por SARS-Cov-2 (MEURI), se requiere que el uso de las intervenciones sea en el marco de ensayos clínicos de adecuado diseño y éticamente aceptables.(AU)

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial / 中华医学杂志(英文版)

BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Therapeutic Effect of Convalescent Plasma Transfusion on Fulminant Viral Infectious Diseases--Review / 中国实验血液学杂志

Novel coronavirus disease 2019 (COVID-19) has started to erupt in Wuhan since December 2019, and then the cases of COVID-19 increased rapidly, the epidemic situation spreaded to most area of China. Owing to the lack of specific drugs at present, convalescent plasma therapy becomes an alternative treatment. However, the choice of the donor, suitable patients, timing of treatment, administrate dose, the advantages and disadvantages of the treatment are not clear. This article reviews the clinical studies and case reports of convalescent plasma therapy in several previous viral infectious diseases in order to provide clues for the treatment of COVID-19.

Antibody indexes in COVID-19 convalescent plasma donors: Unanswered questions

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by high contagiousness, as well as variable clinical manifestations and immune responses. The antibody response to SARS-CoV-2 is directly related to viral clearance and the antibodies' ability to neutralize the virus and confer long-term immunity. Nevertheless, the response can also be associated with disease severity and evolution. This study correlated the clinical characteristics of convalescent COVID-19 patients with immunoglobulin A (IgA) and IgG anti-SARS-CoV-2 antibodies. METHODS: This study included 51 COVID-19 health care professionals who were candidates for convalescent plasma donation from April to June 2020. The subjects had symptomatic COVID-19 with a polymerase chain reaction-confirmed diagnosis. We measured anti-SARS-CoV-2 IgA and IgG antibodies after symptom recovery, and the subjects were classified as having mild, moderate, or severe symptoms. RESULTS: Anti-SARS-CoV-2 antibodies were positive in most patients (90.2%). The antibody indexes for IgA and IgG did not differ significantly between patients presenting with mild or moderate symptoms. However, they were significantly higher in patients with severe symptoms. CONCLUSIONS: Our study showed an association between higher antibody indexes and severe COVID-19 cases, and several hypotheses regarding the association of the antibody dynamics and severity of the disease in SARS-CoV-2 infection have been raised, although many questions remain unanswered.