Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

Influence of epidemiological and clinical factors in the reactogenicity to Comirnaty® vaccine in health care workers of a Spanish university teaching hospital (COVIVAC study) / Influencia de factores epidemiológicos y clínicos en la reactogenicidad a la vacuna Comirnaty® en trabajadores sanitarios de un hospital universitario español (estudio COVIVAC)

Introduction. Comirnaty® is an mRNA vaccine against COVID-19 which has been administered to millions of people since the end of 2020. Our aim was to study epidemiological and clinical factors influencing reactogenicity and functional limitation after the first two doses of the vaccine in health care workers (HCWs). Material and methods. Prospective post-authorization cohort study to monitor safety and effectiveness of the vaccine. Results. Local side effects were mild and presented both with first and second dose of Comirnaty. Systemic side effects were more frequent after 2nd dose. Nevertheless, previous SARS-CoV-2 infection was associated with systemic effects after the first dose of the vaccine (OR ranging from 2 to 6). No severe adverse effects were reported. According to multivariate analysis, the degree of self-reported functional limitation after the first dose increased with age, female sex, previous COVID-19 contact, previous SARS-CoV-2 infection, and Charlson Comorbidity Index (CCI). After the second dose, the degree of functional limitation observed was lower in those with previous SARS-CoV-2 infection, and it was positively associated to the degree of functional limitation after the first dose. Conclusion. Systemic adverse effects were more frequent after the second dose of Comirnaty. Previous SARS-CoV-2 infection was associated with systemic effects after the first dose. Age, female sex, previous COVID-19, previous isolation due to COVID-19 contact, and CCI showed to be independent predictors of the degree of functional limitation after the 1st dose of Comirnaty®. After the 2nd dose, the degree of functional limitation was lower in those who previously had SARS-CoV-2 infection (AU)

Introducción. Comirnaty® es una vacuna de ARNm contra el COVID-19 que se ha administrado a millones de personas desde finales de 2020. Nuestro objetivo fue estudiar los factores epidemiológicos y clínicos que influyen en la reactogenicidad y la limitación funcional asociadas tras las dos primeras dosis de la vacuna en trabajadores de la salud. Metodología. Estudio de cohorte prospectivo post-autorización para evaluar la seguridad y eficacia de la vacuna. Resultados. Los efectos secundarios locales fueron leves y se presentaron tanto con la primera como con la segunda dosis de Comirnaty. Los efectos secundarios sistémicos fueron más frecuentes después de la segunda dosis. No obstante, la infección previa por SARS-CoV-2 se asoció con efectos sistémicos tras la primera dosis de la vacuna (OR de 2 a 6). No se informaron efectos adversos graves. El análisis multivariante demostró que el grado de limitación funcional tras la primera dosis aumentó con la edad, el sexo femenino, contacto previo con COVID-19, la infección previa por SARS CoV-2 y el índice de comorbilidad de Charlson (ICC). Tras la segunda dosis, el grado de limitación funcional observado fue menor en aquellos con infección previa por SARS-CoV-2, y se asoció positivamente al grado de limitación funcional tras la primera dosis.Conclusión. Los efectos adversos sistémicos fueron más frecuentes después de la segunda dosis de Comirnaty. La infección previa por SARS-CoV-2 se asoció con efectos sistémicos después de la primera dosis. La edad, el sexo femenino, infección por COVID-19 previa, el aislamiento previo por contacto de COVID-19 y el ICC se mostraron como predictores independientes del grado de limitación funcional tras la 1ª dosis de Comirnaty®. Después de la 2.ª dosis, el grado de limitación funcional fue menor en los que previamente tenían infección por SARS-CoV-2 (AU)

Trends in COVID-19-related in-hospital mortality in women and men.

INTRODUCTION: Whether political, scientific and medical development in a country is associated with better clinical results according to gender in patients with COVID-19 has not yet been clearly elucidated. OBJECTIVE: To determine the trends of COVID-19-related in-hospital mortality in women and men from March 2020 to February 2022. METHODS: Clinical data of all patients with COVID-19 cared for at 21 Spanish hospitals were used, both of those who were discharged and of those who died during hospitalization. The association between hospital length of stay and mortality was analyzed with logistic regression models. RESULTS: Out of 7,974 patients that were included, 3,234 were women; 928 patients died. A significant decreasing trend in mortality was identified. When the analysis was carried out by gender, no significant mortality trend was found in women (OR = 0.96 [0.90-1.03], p = 0.239), while in men there was a significant decreasing trend identified (OR = 0.87 [0.82-0.92], p < 0.001). CONCLUSION: Health policies, together with clinical and preventive interventions, may explain these results. Response to treatment and behavioral differences may explain why mortality does not decrease for women.

INTRODUCCIÓN: Todavía no se comprende si el desarrollo político, científico y médico en un país se asocia a mejores resultados clínicos de los pacientes con COVID-19 según el sexo. OBJETIVO: Determinar las tendencias de mortalidad hospitalaria asociada a COVID-19 en mujeres y hombres entre marzo de 2020 y febrero de 2022. MÉTODOS: Se utilizaron los datos clínicos de todos los pacientes con COVID-19 atendidos en 21 hospitales españoles, tanto de quienes fueron dados de alta como de quienes fallecieron durante el ingreso. La asociación entre la fecha del ingreso y la mortalidad se analizó con modelos de regresión logística. RESULTADOS: Fueron incluidos 7974 pacientes, de los cuales 3234 fueron mujeres y 928 fallecieron. Se encontró una tendencia significativa y decreciente en la mortalidad según avanzaba la fecha del ingreso. Cuando el análisis se realizó por sexos, no se halló una tendencia significativa en las mujeres (RM = 0.96 [0.90-1.03], p = 0.239), pero sí en los hombres (RM = 0.87 [0.82-0.92], p < 0.001). CONCLUSIÓN: Las políticas de salud, junto con las intervenciones clínicas y preventivas, pueden dar cuenta de los resultados. Diferencias en la respuesta al tratamiento o en los comportamientos pueden explicar por qué la mortalidad no disminuye en las mujeres.

Tendencia de mortalidad hospitalaria por COVID-19 en mujeres y hombres / Trends in COVID-19-related in-hospital mortality in women and men

Resumen Introducción: Todavía no se comprende si el desarrollo político, científico y médico en un país se asocia a mejores resultados clínicos de los pacientes con COVID-19 según el sexo. Objetivo: Determinar las tendencias de mortalidad hospitalaria asociada a COVID-19 en mujeres y hombres entre marzo de 2020 y febrero de 2022. Métodos: Se utilizaron los datos clínicos de todos los pacientes con COVID-19 atendidos en 21 hospitales españoles, tanto de quienes fueron dados de alta como de quienes fallecieron durante el ingreso. La asociación entre la fecha del ingreso y la mortalidad se analizó con modelos de regresión logística. Resultados: Fueron incluidos 7974 pacientes, de los cuales 3234 fueron mujeres y 928 fallecieron. Se encontró una tendencia significativa y decreciente en la mortalidad según avanzaba la fecha del ingreso. Cuando el análisis se realizó por sexos, no se halló una tendencia significativa en las mujeres (RM = 0.96 [0.90-1.03], p = 0.239), pero sí en los hombres (RM = 0.87 [0.82-0.92], p < 0.001). Conclusión: Las políticas de salud, junto con las intervenciones clínicas y preventivas, pueden dar cuenta de los resultados. Diferencias en la respuesta al tratamiento o en los comportamientos pueden explicar por qué la mortalidad no disminuye en las mujeres.

Abstract Introduction: Whether political, scientific and medical development in a country is associated with better clinical results according to gender in patients with COVID-19 has not yet been clearly elucidated. Objective: To determine the trends of COVID-19-related in-hospital mortality in women and men from March 2020 to February 2022. Methods: Clinical data of all patients with COVID-19 cared for at 21 Spanish hospitals were used, both of those who were discharged and of those who died during hospitalization. The association between hospital length of stay and mortality was analyzed with logistic regression models. Results: Out of 7,974 patients that were included, 3,234 were women; 928 patients died. A significant decreasing trend in mortality was identified. When the analysis was carried out by gender, no significant mortality trend was found in women (OR = 0.96 [0.90-1.03], p = 0.239), while in men there was a significant decreasing trend identified (OR = 0.87 [0.82-0.92], p < 0.001). Conclusion: Health policies, together with clinical and preventive interventions, may explain these results. Response to treatment and behavioral differences may explain why mortality does not decrease for women.

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases.

COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

Longwise Cluster Analysis for the Prediction of COVID-19 Severity within 72 h of Admission: COVID-DATA-SAVE-LIFES Cohort.

The use of routine laboratory biomarkers plays a key role in decision making in the clinical practice of COVID-19, allowing the development of clinical screening tools for personalized treatments. This study performed a short-term longitudinal cluster from patients with COVID-19 based on biochemical measurements for the first 72 h after hospitalization. Clinical and biochemical variables from 1039 confirmed COVID-19 patients framed on the "COVID Data Save Lives" were grouped in 24-h blocks to perform a longitudinal k-means clustering algorithm to the trajectories. The final solution of the three clusters showed a strong association with different clinical severity outcomes (OR for death: Cluster A reference, Cluster B 12.83 CI: 6.11−30.54, and Cluster C 14.29 CI: 6.66−34.43; OR for ventilation: Cluster-B 2.22 CI: 1.64−3.01, and Cluster-C 1.71 CI: 1.08−2.76), improving the AUC of the models in terms of age, sex, oxygen concentration, and the Charlson Comorbidities Index (0.810 vs. 0.871 with p < 0.001 and 0.749 vs. 0.807 with p < 0.001, respectively). Patient diagnoses and prognoses remarkably diverged between the three clusters obtained, evidencing that data-driven technologies devised for the screening, analysis, prediction, and tracking of patients play a key role in the application of individualized management of the COVID-19 pandemics.

Liver status and outcomes in patients without previous known liver disease receiving anticoagulant therapy for venous thromboembolism.

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10-2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04-2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation.

Proinflammatory and Hepatic Features Related to Morbidity and Fatal Outcomes in COVID-19 Patients.

OBJECTIVE: to screen putative associations between liver markers and proinflammatory-related features concerning infectious morbidity and fatal outcomes in COVID-19 patients. METHODS: a total of 2094 COVID-19 positive patients from the COVID-DATA-SAFE-LIFES cohort (HM hospitals consortium) were classified according to median values of hepatic, inflammatory, and clinical indicators. Logistic regression models were fitted and ROC cures were generated to explain disease severity and mortality. RESULTS: intensive care unit (ICU) assistance plus death outcomes were associated with liver dysfunction, hyperinflammation, respiratory insufficiency, and higher associated comorbidities. Four models including age, sex, neutrophils, D-dimer, oxygen saturation lower than 92%, C-reactive protein (CRP), Charlson Comorbidity Index (CCI), FIB-4 and interactions with CRP, neutrophils, and CCI explained ICU plus death variance in more than 28%. The predictive values of ROC curves were: FIB-4 (0.7339), AST/ALT ratio (0.7107), CRP (0.7003), CCI index (0.6778), neutrophils (0.6772), and platelets (0.5618) concerning ICU plus death outcomes. CONCLUSIONS: the results of this research revealed that liver and proinflammatory features are important determinants of COVID-19 morbidity and fatal outcomes, which could improve the current understanding of the COVID-19 physiopathology as well as to facilitate the clinical management and therapy decision-making of this disease under a personalized medicine scope.