RESUMEN
Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, convergent studies have provided evidence that host genetic background may contribute to the development of severe coronavirus disease (COVID-19). Here, we summarize how some genetic variations, such as in SARS-CoV-2 receptor angiotensin-converting enzyme 2 or interferon signaling pathway, may help to understand why some individuals can develop severe COVID-19.
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While tolerance to COVID-19 vaccination is considered satisfactory, a phenomenon of myocarditis, although rare, is becoming a safety concern in mRNA COVID-19 vaccination. The presence of low residual levels of double-strand RNA (dsRNA) has been reported in mRNA COVID-19 vaccine preparations. dsRNA is a known inducer of immune-inflammatory reactions. dsRNA present in vaccine nanoparticles may be suspected to be at the origin of the still unexplained cases of myocarditis.
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The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise in each treatment modality. Our conclusion is that caution should be exercised when combining both treatments.
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Vacuna BNT162/efectos adversos , COVID-19/prevención & control , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/terapia , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Terapia Combinada/efectos adversos , Síndrome de Liberación de Citoquinas/etiología , Interacciones Farmacológicas , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inmunoterapia/métodos , Neoplasias/inmunologíaRESUMEN
PURPOSE: The present study was performed to examine relationships between systemic exposure of capecitabine metabolites (5-FU, 5'-DFCR and 5'-DFUR) and toxicity or clinical response in patients with metastatic breast cancer. METHODS: A population pharmacokinetic model for capecitabine and its three metabolites was built. Typical parameter values, characteristics of random distributions, associated with parameters, and covariates impact were estimated. Area under the curve (AUC) were computed for 5-FU and compared with grades of toxicity. Pharmacokinetic modeling was based on data collected on the first treatment cycle. Toxicity was assessed on the two first treatment cycles. RESULTS: The study was conducted in 43 patients. The population pharmacokinetic model (a one-compartment model per compound) was able to capture the very complex absorption process of capecitabine. Statistically significant covariates were cytidine deaminase, alkaline phosphatase and dihydrouracilemia (UH2)/uracilemia (U) ratio. UH2/U ratio was the most significant covariate on 5-FU elimination and CDA on the transformation of 5'-DFCR in 5'-DFUR. A trend was observed between 5-FU AUC and thrombopenia toxicity grades, but not with other toxicities. Best clinical response was not linked to systemic exposure of capecitabine metabolites. CONCLUSION: In our study, we propose a model able to describe, meanwhile, and its main metabolites, with a complex absorption process and inclusion of enzyme activity covariates such as CDA and UH2/U ratio. Trial registration Eudract 2008-004136-20, 2008/11/26.
Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/farmacocinética , Modelos Biológicos , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Área Bajo la Curva , Capecitabina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/sangre , Femenino , Floxuridina/sangre , Fluorouracilo/sangre , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Tratamiento Farmacológico de COVID-19RESUMEN
To uncover the key cellular pathways associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity, Daniloski and coworkers used CRISPR-based whole-genome screening. Their results could propose new or repositioned drugs for the ongoing fight against COVID-19.
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Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Genoma Viral/genética , Estudio de Asociación del Genoma Completo/métodos , SARS-CoV-2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virología , Sistemas CRISPR-Cas , Edición Génica/métodos , Expresión Génica , Humanos , Interferencia de ARN , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologíaRESUMEN
Cancer patients are vulnerable to COVID-19 with consequences on treatment delays and on mortality rate. This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.
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Proteína ADAM17/genética , COVID-19/genética , Neoplasias/genética , Serina Endopeptidasas/genética , Enzima Convertidora de Angiotensina 2/genética , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/virología , Humanos , Mortalidad , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/virología , SARS-CoV-2/genética , SARS-CoV-2/patogenicidadRESUMEN
Patients with cancer should benefit from COVID-19 vaccination. Some of the most advanced vaccine candidates are mRNAs encapsulated into lipid carriers, and small liposomes are expected to accumulate in tumour tissues through the enhanced and permeation retention effect. However, to what extent solid tumours could take up a significant part of the vaccine dose as well remains unknown. This calls for a careful evaluation of the efficacy of these promising mRNA COVID-19 vaccines administered as lipid carriers for patients with solid tumours, including a possible re-appraisal of the dosing for optimal protection of this specific and frail population.
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Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Portadores de Fármacos , Neoplasias/terapia , SARS-CoV-2/inmunología , Aceleración , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Portadores de Fármacos/normas , Fragilidad/epidemiología , Fragilidad/terapia , Humanos , Programas de Inmunización/normas , Liposomas/administración & dosificación , Liposomas/efectos adversos , Neoplasias/epidemiología , Neoplasias/inmunología , Pandemias , ARN Mensajero/administración & dosificación , ARN Mensajero/normas , Factores de Tiempo , Vacunación/métodosRESUMEN
Based on a broad public database compilation, we support the hypothesis that germinal polymorphisms may regulate the expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular target itself and proteases controlling the process of its shedding or, conversely, its internalization. Consequently, a genetic influence on individual susceptibility to coronavirus disease 2019 (COVID-19) infection is strongly suspected.