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PURPOSE: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. METHODS: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease. RESULTS: Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection. CONCLUSIONS: A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease.

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The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the population has affected the supply chains of these life-saving medical products. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. We also review different aspects of CAR T-cell therapy and our managerial experience of patient selection, resource prioritization and some practical aspects to consider for safe administration. Although hospitals have been forced to change their usual workflows to cope with the saturation of health services by hospitalized patients, we recommend centers to continue offering this potentially curative treatment for patients with relapsed/refractory hematologic malignancies. Consequently, we propose appropriate selection criteria, early intervention to attenuate neurotoxicity or cytokine release syndrome with tocilizumab and prophylactic/preventive strategies to prevent infection. These considerations may apply to other emerging adoptive cell treatments and the corresponding manufacturing processes.

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Introducción: La exposición a agentes biológicos y químicos, en laboratorios, representan un alto nivel de riesgo para la salud e integridad de las personas y constituyen un aspecto importante en el establecimiento de un adecuado Programa de Bioseguridad. Objetivos: la presente investigación es caracterizar los factores de riesgo químico y biológico en los laboratorios de morfología y microbiología de una Universidad, mediante un estudio de enfoque empírico analítico de tipo descriptivo y transversal, donde se identificó los factores de riesgo y las condiciones de bioseguridad de los laboratorios, implementando las directrices de la GTC 45: 2012, a fin de evaluar los niveles de riesgo del factor químico y biológico, empleando la metodología de la OMS y Normas Técnicas del INSHT de España, para categorizar los agentes patógenos por grupos de riesgo, establecer los niveles de contención actual de los laboratorios y definir los efectos de mayor prevalencia en la salud y/o el medio ambiente. Resultados: Se identificaron 36 factores de riesgo biológico (FRB) y 63 Factores de Riesgo Químico (FRQ). El laboratorio de Microbiología presentó 2 agentes con Nivel de Riesgo (NR) I y 10 NR II, del cual 10.1% son no aceptables y 21.3% aceptables con controles, 96% de los agentes biológicos pertenecen al Grupo de Riesgo (GR) 2 y 4% al GR 3. El laboratorio de Morfología mostró 16.67% de factores en NR I y II, el 10% corresponde a FRQ, 40% son no aceptables, 67%

Introduction: Human exposure to biological and chemical agents represent a high level of risk to the health and integrity at laboratories facilities, also constitute an important aspect in the establishment of an adequate Biosecurity Program. Objetive: the purpose of this research is to characterize the chemical and biological risk factors at the morphology and microbiology laboratories of a University, using a descriptive transversal analytical and empirical study, where the risk levels and biosafety conditions of the laboratories were diagnosed implementing the guidelines of the GTC 45: 2012, in order to evaluate the risk levels of the chemical and biological factors, in conjunction with the methodology of the WHO and Technical Standards of the INSHT of Spain, to categorize the pathogenic agents by risk groups, establish the levels of current containment of laboratories and define the effects of higher prevalence on health and/or the environment. Results: 36 Biological Risk Factors (BRF) and 63 Chemical Risk Factors (CRF) were found. Microbiological Laboratory showed 2 agents with Risk Level (RL) I and RL II, in which a 10.1% were Not Acceptable and 21.3% were Acceptable With Controls, 96% of Biological Agents belong to Risk Group (RG) 2 and 4% to RG 3. Morphology Laboratory revealed 16.67% between RL I and II, 10% belong to CRF, 40% were Not Acceptable, 67% of the agents were categorized as RG 2 and 33% as RG 3.

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