ABSTRACT
Background and importance Remdesivir is currently included in clinical guidelines for COVID-19 treatment. Although safety data were published in ACTT-1, the toxicity of this drug in regular clinical practice is still unknown. Aim and objectives In this study we aimedd to describe remdesivir's toxicity in patients only requiring supplemental lowflow oxygen (no high-flow oxygen requirements or other noninvasive ventilation at start of treatment). Material and methods Retrospective cohort including patients treated with remdesivir following Spanish Medicines and Health Products Agency criteria (non-critical patients requiring low-flow oxygen) between August and October 2020 in a tertiary- level hospital. Exclusion criteria were being under 18 years of age and participation in clinical trials with remdesivir. The percentage of adverse reactions occurring in the 14 days following on from the beginning of treatment was the primary outcome. Secondly, the number of treatment discontinuations were assessed. Categorical variables were expressed as proportions while continuous values were formulated as median and interquartile range (IQR). Results 264 patients were included (59.2% men, mean age 66 years;IQR 54-82). In the 14 days following on from the beginning of treatment, an adverse reaction (AR) was reported in 146 (55.3%) patients. In 91 (34.5%) of them it was grade ≥2 AR, in 31 (11.7%) grade ≥3 and in 8 (3.0%) of them grade ≥4. Median of days until toxicity began was 3.5 days (IQR 1.2-9.0). The most common AR was an increase in transaminases, which happened in 114 (43.2%) patients, 29.1% of them being grade ≥3 and 3.9% grade ≥4. Regarding renal toxicity, an increase in serum creatinine occurred in 51 (19.8%) patients, 27.5% of them being grade ≥3 and 9.8% grade ≥4. One patient suffered a grade 3 anaphylactic reaction during infusion and another one developed hepatitis during the follow-up period. Two more patients suffered gastrointestinal toxicity (grade 1-2 nausea and diarrhoea). During the study period, 31 (12.1%) patients discontinued remdesivir treatment,12.5% of them due to AR or toxicity related to the drug. Conclusion and relevance Increased transaminases was the most common AR in this population, matching remdesivir's European Public Assessment Report (EPAR) specifications, followed by an increase in the serum creatinine levels (frequency not detailed on the EPAR). However, only 12.5% of treatment discontinuations were due to adverse reactions or toxicity linked to remdesivir. Further investigation is needed to unravel the degree of involvement of the drug in this toxicity.
ABSTRACT
OBJECTIVE: To determine the baseline characteristics associated with higher mortality at 42 days in patients hospitalized for COVID-19 in Spain. METHOD: The study analyzed a prospective cohort of hospitalized COVID-19 patients. The dependent variable was 42-day mortality. Data on the subjects' demographic and clinical characteristics, comorbidities, usual therapy and supportive interventions and treatments was collected within 48 hours from admission. To determine the potential association of the data with mortality, a multivariate analysis was performed using logistic regression. RESULTS: 15,628 patients were included, 18.2% of whom (n = 2,806) died during the study period. According to the multivariate analysis, the variables that were significantly associated (p < 0.05) with mortality upon admission were: being referred from a nursing home (OR 1.9);having a high respiratory rate (OR 1,5);having moderate (OR 1.7) or severe (OR 2.9) pneumonia (CURB-65);aspartate aminotransferase transaminase ≥ 100 IU/l (OR 2.1); lactate dehydrogenase ≥ 360 IU/L (OR 1.6);procalcitonin > 0.5 ng/mL (OR 1.8);creatine kinase ≥ 294 U/L (OR 1.5);D-dimer > 3,000 ng/mL (OR 1.5); hemoglobin < 11.6 g/dL (OR 1.4) and C-reactive protein > 120 mg/L (OR 1.2; requiring respiratory support within the first 48 hours (oxygen therapy [OR 2.0], non-invasive ventilation [OR 2.8], and mechanical ventilation [OR 3.5]); and being treated with interferon-beta (OR 1.5). On the contrary, being under 80 years of age was associated with lower mortality. CONCLUSIONS: The analysis, based on the data in the RERFAR registry, showed that the factors associated with poorer prognosis were older age, assessed using the CURB-65 scale, level of respiratory support required, severe pneumonia (CURB-65), hypertransaminasemia, elevated creatine kinase, lactate dehydrogenase, and D-dimer levels, anemia, and elevated respiratory rate. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved. OBJETIVO: Determinar las características basales que se asocian a una mayor mortalidad a los 42 días en aquellos pacientes hospitalizados por COVID-19 en España.Método: Cohorte prospectiva de pacientes COVID-19 hospitalizados. La variable dependiente fue la mortalidad a los 42 días. Además, se recogieron características demográficas, clínicas, comorbilidades, tratamiento habitual, intervenciones de soporte y tratamientos en las primeras 48 horas del ingreso. Para determinar la asociación con la mortalidad, se realizó un análisis multivariante mediante regresión logística. Resultados: Se incluyeron 15.628 pacientes, de ellos falleció el 18,2% (n = 2.806). El análisis multivariante mostró que las variables asociadas significativamente (p < 0,05) con la mortalidad al ingreso fueron: proceder de un centro sociosanitario (odds ratio OR 1,9), frecuencia respiratoria (odds ratio 1,5), gravedad de neumonía (CURB-65) moderada (odds ratio 1,7) o alta (odds ratio 2,9), transaminasa aspartato aminotransferasa ≥ 100 UI/l (odds ratio 2,1), lactato-deshidrogenasa ≥ 360 UI/l (odds ratio 1,6), procalcitonina > 0,5 ng/ml (odds ratio 1,8), creatina- quinasa ≥ 294 U/l (odds ratio 1,5), dímero D > 3.000 ng/ml (odds ratio 1,5), hemoglobina < 11,6 g/dl (odds ratio 1,4) y proteína C reactiva > 120 mg/l (odds ratio 1,2), necesidad de soporte respiratorio en las primeras 48 horas (odds ratio 2,0 de oxigenoterapia;odds ratio 2,8 ventilación no invasiva y odds ratio 3,5 ventilación mecánica) y tratamiento con interferón-beta (odds ratio 1,5). Por el contrario, ser menor de 80 años se asoció a una menor mortalidad. Conclusiones: El análisis del Registro Español de Resultados de farmacoterapia frente a COVID-19 muestra que los factores asociados a peor pronóstico son: mayor edad, valoración mediante la escala CURB‑65, el nivel de requerimiento de soporte respiratorio, neumonía grave (CURB‑65), hipertransaminasemia, elevación de creatina-quinasa, lactato- deshidrogenasa, y dímero-D, anemia y elevación de la frecuencia respiratoria.
ABSTRACT
Objective: To determine the baseline characteristics associated with higher mortality at 42 days in patients hospitalized for COVID-19 in Spain. Method: The study analyzed a prospective cohort of hospitalized COVID-19 patients. The dependent variable was 42-day mortality. Data on the subjects' demographic and clinical characteristics, comorbidities, usual therapy and supportive interventions and treatments was collected within 48 hours from admission. To determine the potential association of the data with mortality, a multivariate analysis was performed using logistic regression. Results: 15,628 patients were included, 18.2% of whom (n = 2,806) died during the study period. According to the multivariate analysis, the variables that were significantly associated (p < 0.05) with mortality upon admission were: being referred from a nursing home (OR 1.9);having a high respiratory rate (OR 1,5);having moderate (OR 1.7) or severe (OR 2.9) pneumonia (CURB-65);aspartate aminotransferase transami- nase >= 100 IU/l (OR 2.1);lactate dehydrogenase >= 360 IU/L (OR 1.6);procalcitonin > 0.5 ng/mL (OR 1.8);creatine kinase >= 294 U/L (OR 1.5);D-dimer > 3,000 ng/mL (OR 1.5);hemoglobin < 11.6 g/dL (OR 1.4) and C-reactive protein > 120 mg/L (OR 1.2;requiring respiratory support within the first 48 hours (oxygen therapy [OR 2.0], non-invasive ventilation [OR 2.8], and mechanical ventilation [OR 3.5]);and being treated with interferon-beta (OR 1.5). On the contrary, being under 80 years of age was associated with lower mortality. Conclusions: The analysis, based on the data in the RERFAR registry, showed that the factors associated with poorer prognosis were older age, assessed using the CURB-65 scale, level of respiratory support required, severe pneu-monia (CURB-65), hypertransaminasemia, elevated creatine kinase, lactate and D-dimer levels, anemia, and elevated rate.