ABSTRACT
BACKGROUND: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab-cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab-cilgavimab in preventing progression to severe COVID-19 or death. METHODS: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab-cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. FINDINGS: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab-cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab-cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6-71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1-8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab-cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab-cilgavimab group and six in the placebo group. INTERPRETATION: A single intramuscular tixagevimab-cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab-cilgavimab might lead to more favourable outcomes. FUNDING: AstraZeneca.
Subject(s)
COVID-19 Drug Treatment , Adult , Antibodies, Monoclonal/therapeutic use , Double-Blind Method , Humans , Middle Aged , Outpatients , SARS-CoV-2 , Treatment OutcomeABSTRACT
In late December 2019, COVID-19, a new emerging disease, quickly spread in Wuhan, China. The WHO formally declared it a pandemic and a health emergency on March 11th, 2020. The objective of this article is to specify and list key points in relation to the recommendations issued by the different colleges, and global surgical societies, for the benefit of the Mexican medical and surgical community. Based on scientific evidence, we make recommendations for medical consultations, surgical and endoscopic procedures, hospital infrastructure, and surgical services, in addition to a proposal to reopen surgical services and elective procedures related to the COVID-19 pandemic. The time to take leadership in healthcare where the national health system together with academic societies, universities and private initiative join forces to combat the pandemic has arrived. It is convenient to form collaboration groups of experts in the different specialties that through innovation in health and education, with evidence-based medicine, efficiency of operational costs and tools such as telemedicine, allow us to return to daily surgical procedures, reestablishing the surgery services as soon as possible.
A finales de diciembre de 2019, la COVID-19, una nueva enfermedad emergente, rápidamente se propagó en Wuhan, China. La Organización Mundial de la Salud la declaró formalmente una pandemia y emergencia sanitaria el 11 de marzo de 2020. El objetivo de este artículo es precisar y enumerar los puntos clave en relación a las recomendaciones emitidas por los distintos colegios, y sociedades quirúrgicas globales, para beneficio de la comunidad médica y quirúrgica mexicana. De acuerdo con la evidencia científica, se realizan recomendaciones para las consultas médicas, los procedimientos quirúrgicos y endoscópicos, la infraestructura hospitalaria y los servicios de cirugía, además de una propuesta a la reapertura para procedimientos quirúrgicos en torno a la pandemia de COVID-19. El momento de tomar el liderazgo en salud en el que el sistema nacional de salud y las sociedades académicas, las universidades y la iniciativa privada sumen esfuerzos para combatir la pandemia ha llegado. Es conveniente formar grupos de colaboración de expertos en las distintas especialidades que, por medio de innovación en salud y educación, apego a la medicina basada en la evidencia, eficiencia de costos operacionales y herramientas como la telemedicina, permitan regresar a los procedimientos quirúrgicos cotidianos y la operación de los servicios de cirugía se reestablezca a la brevedad.
Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Elective Surgical Procedures , Leadership , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Serological Testing , Cause of Death , Chronic Disease , Endoscopy , Evidence-Based Medicine , Humans , Mexico , Patient Care Team , Practice Guidelines as TopicABSTRACT
Throughout history, pandemics have had a major impact on humanity. The measures used to combat them cause collateral damage. During the COVID-19 pandemic, the actions taken to reduce the exposure, the number of infections, and the case fatality rate focus on reducing mortality, however, the collapse of the health system can cause an even greater number of deaths. At the same time, both medical personnel and patients are affected by the economic slowdown and the "effect of negativity". In this review article the different tools available for pandemic control, their development in a historical context, and how they may impact risk stratification for vulnerable patients (elderly, patients with chronic degenerative and oncological diseases) were analyzed.
A lo largo de la historia, las pandemias han tenido un gran impacto para la humanidad. Las medidas utilizadas para combatirlas causan daño colateral. En la pandemia por COVID-19, las acciones generadas para disminuir la exposición, el número de contagios y la tasa de letalidad conllevan un enfoque en la reducción de la mortalidad, sin embargo el colapso del sistema de salud puede provocar un número aún mayor de muertos. A su vez, tanto el personal médico como los pacientes se ven afectados por la desaceleración económica y el "efecto de la negatividad". En este artículo de revisión se analizaron las diferentes herramientas para el control de la pandemia, su desarrollo en un contexto histórico y como impactan en la estratificación del riesgo para pacientes vulnerables (ancianos, pacientes con enfermedades crónico degenerativas y oncológicos).
Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Chronic Disease , Delivery of Health Care , SARS-CoV-2 , COVID-19/mortality , Chronic Disease/therapy , Economic Recession , Hospitalization , Humans , National Health Programs , Risk Assessment , Vulnerable PopulationsABSTRACT
A review is carried out to examine the risk of patients suffering from diabetes mellitus in the context of general morbidity and mortality and related to infection by SARS-CoV-2. Likewise, the general recommendations for food and the prevention of comorbidities that most these patients suffer most frequently are also studied. Finally, a review of the pharmacological recommendations on both oral and parenteral treatment in the outpatient, in hospitalization and in critical states infected with SARS-CoV-2 is made.
Se realiza una revisión sobre el riesgo de los pacientes que padecen diabetes mellitus en el contexto de morbimortalidad general y relacionada a infección por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). Así mismo se repasan las recomendaciones generales, de alimentación y de la prevención de las comorbilidades que más frecuentemente padecen dichos enfermos. Finalmente se hace una revisión de las recomendaciones farmacológicas sobre el tratamiento tanto oral como parenteral en el paciente ambulatorio, en la hospitalización y en estados críticos infectados por el SARS-CoV-2.