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(1) Background: C-reactive protein (CRP) and albumin are inflammatory markers. We analyzed the prognostic capacity of serum albumin (SA) and CRP for an outcome comprising mortality, length of stay, ICU admission, and non-invasive mechanical ventilation in hospitalized COVID-19 patients. (2) Methods: We conducted a retrospective cohort study based on the Spanish national SEMI-COVID-19 Registry. Two multivariate logistic models were adjusted for SA, CRP, and their combination. Training and testing samples were used to validate the models. (3) Results: The outcome was present in 41.1% of the 3471 participants, who had lower SA (mean [SD], 3.5 [0.6] g/dL vs. 3.8 [0.5] g/dL; p < 0.001) and higher CRP (108.9 [96.5] mg/L vs. 70.6 [70.3] mg/L; p < 0.001). In the adjusted multivariate model, both were associated with poorer evolution: SA, OR 0.674 (95% CI, 0.551–0.826; p < 0.001); CRP, OR 1.002 (95% CI, 1.001–1.004; p = 0.003). The CRP/SA model had a similar predictive capacity (honest AUC, 0.8135 [0.7865–0.8405]), with a continuously increasing risk and cutoff value of 25 showing the highest predictive capacity (OR, 1.470; 95% CI, 1.188–1.819; p < 0.001). (4) Conclusions: SA and CRP are good independent predictors of patients hospitalized with COVID-19. For the CRP/SA ratio value, 25 is the cutoff for poor clinical course.

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5–58.9) to 57.1 (44.1–67.1) vs. 71.5 (59.5–81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10–0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17–1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26–2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21–1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often.

Background: The WHO ordinal severity scale has been used to predict mortality and guide trials in COVID-19. However, it has its limitations. Objective The present study aims to compare three classificatory and predictive models: the WHO ordinal severity scale, the model based on inflammation grades, and the hybrid model. Design Retrospective cohort study with patient data collected and followed up from March 1, 2020, to May 1, 2021, from the nationwide SEMI-COVID-19 Registry. The primary study outcome was in-hospital mortality. As this was a hospital-based study, the patients included corresponded to categories 3 to 7 of the WHO ordinal scale. Categories 6 and 7 were grouped in the same category. Key Results A total of 17,225 patients were included in the study. Patients classified as high risk in each of the WHO categories according to the degree of inflammation were as follows: 63.8% vs. 79.9% vs. 90.2% vs. 95.1% (p

Objective To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Methods Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Results Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59–79] vs 73 years [IQR 61–83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91–2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75–0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32–1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71–0.95; p < .001 and OR 0.80 95% CI 0.65–0.97; p < .001) respectively. Conclusion There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Farmacología. Fecha de Lectura: 02-12-2022, Varios ensayos clínicos han demostrado peor evolución clínica y menor respuesta a la quimioterapia (quimiorresistencia), incluyendo a los derivados del platino, de los pacientes con cáncer de pulmón de células no pequeñas (NSCLC) fumadores frente a no fumadores. Datos preliminares in vitro de nuestro laboratorio han revelado que la nicotina del tabaco, y su nitrosamina derivada NNK, a través de la activación de receptores nicotínicos para la acetilcolina del subtipo α7 (α7-nAChRs) expresados en las células epiteliales y tumorales de pulmón, están implicadas en la anterior quimiorresistencia al interferir con el efecto citotóxico de cisplatino a nivel de la apoptosis. Sin embargo, se desconocen los mecanismos moleculares puestos en marcha por el α7-nAChR para interferir con el efecto proapoptótico de cisplatino, o si dicha resistencia a cisplatino mediada por el anterior subtipo de receptor se reproduce in vivo. También permanece por dilucidar si otros subtipos del nAChR, distintos al α7-nAChR, contribuyen a la anterior quimiorresistencia, así como si los hallazgos in vitro e in vivo relativos al mecanismo molecular implicado en la quimiorresistencia pueden ser corroborados en la clínica. En base a lo anterior, esta Tesis Doctoral tiene como OBJETIVO GENERAL tratar de resolver las cuatro incógnitas planteadas. Con este propósito hemos realizado experimentos in vitro utilizando diversas variantes de la línea celular humana de adenocarcinoma de pulmón A549 [salvaje, o con distintas subunidades del nAChR (α3, α5, β4, α7) silenciadas con siRNAs específicos (knockdown) o mediante CRISPR-Cas9 (knockout)], junto a experimentos in vivo en un modelo xenográfico murino de NSCLC, combinados con experimentos en tumores primarios de 107 pacientes con NSCLC, tanto fumadores (n = 59) como no fumadores (n = 48). En los experimentos in vitro e in vivo se ha empleado cisplatino como agente quimioterápico, y en el conjunto de la Tesis una combinación de técnicas que incluyen la PCR cuantitativa, citometría de flujo, microarrays proteicos, inmunoblot, inmunohistoquímica y ensayos de tumorogenicidad. Nuestros principales hallazgos son los siguientes: (i) se identifican las proteínas quinasas y factores de transcripción cuya actividad es desregulada por nicotina, a través del α7-nAChR, promoviendo la supervivencia celular y, por tanto, contrarrestando el efecto citotóxico de cisplatino; (ii) se corrobora in vivo el papel determinante del α7-nAChR en la resistencia a cisplatino inducida por nicotina en el tumor xenográfico NSCLC del ratón; (iii) se constata, también in vivo, que en la resistencia a cisplatino inducida por nicotina subyace un aumento de expresión de proteínas antiapoptóticas y disminución de las proapoptóticas en el tumor xenográfico; (iv) la anterior alteración del patrón de expresión génica de proteínas reguladoras de apoptosis inducida por nicotina in vivo es corroborada en tumores primarios NSCLC de fumadores frente a no fumadores; (v) se demuestra que otros subtipos de nAChRs, además del α7-nAChR, contribuyen a la anterior quimiorresistencia. En conjunto, nuestros resultados in vitro, in vivo y en tumores primarios de pacientes con NSCLC revelan el mecanismo molecular que subyace en la resistencia a la quimioterapia inducida por el consumo de tabaco en este tipo de tumor. A través de este mecanismo, los componentes del tabaco nicotina/NNK, activando α7-nAChRs y otros subtipos de nAChRs, alterarían la capacidad apoptótica celular generando un “estado antiapoptótico” en el tumor que lo haría refractario al efecto citotóxico de la quimioterapia. En base a nuestros hallazgos, la presente Tesis aporta argumentos científicos sólidos para concienciar a médicos, pacientes, y población en general, acerca de que el consumo de tabaco no solo es la principal causa prevenible de cáncer y muerte por cáncer, sino también del previsible fracaso terapéutico y peor evolución que este hábito puede ocasionaren en los pacientes con NSCLC y otros tumores asociados al tabaquismo, La presente Tesis Doctoral ha sido financiada por el Ministerio de Ciencia e Innovación de España bajo el proyecto SAF2017SAF2017-8268982689-R