Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: An open-label randomised trial.

BACKGROUND: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. METHODS: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. RESULTS: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; p = 0.007). CONCLUSIONS: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

BACKGROUND: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. METHODS: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. RESULTS: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). CONCLUSIONS: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.

N-antigenemia detection by a rapid lateral flow test predicts 90-day mortality in COVID-19: A prospective cohort study.

OBJECTIVES: To evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards. METHODS: The presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis. RESULTS: Prevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09-3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26-0.85). DISCUSSION: The presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.

Impact of atmospheric nitrogen dioxide on emergency department visits for asthma in a low air pollution area: a time series and case-crossover study. / Influencia del dióxido de nitrógeno ambiental en las consultas a urgencias por asma en un entorno con baja contaminación: análisis de series temporales y casos cruzados.

OBJECTIVES: To analyze the association between atmospheric levels of nitrogen dioxide (NO2) and the number of visits by adults to an emergency department (ED) for exacerbated asthma in an urban area with low levels of air pollution. MATERIAL AND METHODS: Retrospective ecological time-series study. We quantified ED visits for asthma by consecutive patients over the age of 14 years between 2010 and 2018 (3287 days). The association between the mean atmospheric concentration of NO2 and the number of daily visits to the ED for asthma was analyzed with generalized linear regression analysis (Poisson modeling). The impact of exposure on individual risk was assessed by crossover analysis of case periods. We adjusted for confounding meteorologic variables, potential variability due to seasonal changes was corrected by trend analysis, and 3 time lags were assessed (0, 1, and 3 days). RESULTS: We analyzed 2527 asthma emergencies in 1588 patients (70% female) with a mean (SD) age of 51 (21) years. A significant positive association (relative risk, 1.056, 95% CI, 1.006-1.108; P .05) between atmospheric NO2 concentration and greater risk of visiting an ED within 3 days was detected. An increase of 10 µg/m3 of NO2 accounted for 5.3% of the visits (attributable fraction, 5.30, 95% CI, 0.60-9.75; P .05). CONCLUSION: In an urban area with low pollution levels, an elevation in atmospheric NO2 is associated with more hospital ED visits for asthma attacks in adults.

OBJETIVO: Analizar la asociación entre los niveles ambientales de dióxido de nitrógeno (NO2) y el número de consultas a urgencias por un episodio de agudización de asma bronquial en la población adulta de un entorno urbano con bajos niveles de contaminación. METODO: Estudio ecológico retrospectivo de series temporales. Se consideraron las visitas por asma de pacientes mayores de 14 años que acudieron a un servicio de urgencias de forma consecutiva entre 2010 y 2018 (3.287 días). La asociación entre la concentración media de NO2 y el número diario de visitas a urgencias por asma se estudió mediante un modelo lineal generalizado con regresión de Poisson. Se evaluó el impacto en el riesgo individual mediante un análisis de casos cruzados. Se ajustó por las variables confusoras meteorológicas, se corrigió la estacionalidad mediante análisis de tendencias y se evaluaron tres lags temporales (0, 1 y 3 días). RESULTADOS: Se analizaron 2.527 urgencias por asma correspondientes a 1.588 pacientes (edad media 51 ± 21 años, 70% mujeres). Hubo una asociación positiva significativa (riesgo relativo: RR = 1,056, IC 95%: 1,006-1,108; p 0,05) entre la concentración de NO2 y un mayor riesgo de consulta a urgencias por asma a los 3 días. Un incremento de 10 µgr/m3 de NO2 explicó el 5,3% de las consultas (fracción atribuible: FA = 5,30, IC 95%: 0,60-9,75; p 0,05). CONCLUSIONES: El incremento de los niveles ambientales de NO2 se asocia con un mayor número de urgencias hospitalarias por exacerbación de asma en adultos en un entorno con baja contaminación.

Risk models for predicting in-hospital mortality from COVID-19 pneumonia in the elderly. / Modelos de riesgo para la predicción de mortalidad hospitalaria en ancianos con neumonía por COVID-19.

OBJECTIVES: To compare the prognostic value of 3 severity scales: the Pneumonia Severity Index (PSI), the CURB-65 pneumonia severity score, and the Severity Community-Acquired Pneumonia (SCAP) score. To build a new predictive model for in-hospital mortality in patients over the age of 75 years admitted with pneumonia due to the coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: Retrospective study of patients older than 75 years admitted from the emergency department for COVID-19 pneumonia between March 12 and April 27, 2020. We recorded demographic (age, sex, living in a care facility or not), clinical (symptoms, comorbidities, Charlson Comorbidity Index [CCI]), and analytical (serum biochemistry, blood gases, blood count, and coagulation factors) variables. A risk model was constructed, and the ability of the 3 scales to predict all-cause in-hospital mortality was compared. RESULTS: We included 186 patients with a median age of 85 years (interquartile range, 80-89 years); 44.1% were men. Mortality was 47.3%. The areas under the receiver operating characteristic curves (AUCs) were as follows for each tool: PSI, 0.74 (95% CI, 0.64-0.82); CURB-65 score, 0.71 (95% CI, 0.62-0.79); and SCAP score, 0.72 (95% CI, 0.63-0.81). Risk factors included in the model were the presence or absence of symptoms (cough, dyspnea), the CCI, and analytical findings (aspartate aminotransferase, potassium, urea, and lactate dehydrogenase. The AUC for the model was 0.81 (95% CI, 0.73-0.88). CONCLUSION: This study shows that the predictive power of the PSI for mortality is moderate and perceptibly higher than the CURB-65 and SCAP scores. We propose a new predictive model for mortality that offers significantly better performance than any of the 3 scales compared. However, our model must undergo external validation.

OBJETIVO: Los objetivos son comparar la utilidad pronóstica de tres escalas de gravedad (Pneumonia Severity Index: PSI; CURB-65 scale; Severity Community Acquired Pneumonia Score: SCAP) y diseñar un nuevo modelo predictivo de mortalidad hospitalaria en pacientes mayores de 75 años ingresados por neumonía por COVID-19. METODO: Estudio retrospectivo de pacientes mayores de 75 años ingresados por neumonía por COVID-19 desde el servicio de urgencias entre el 12 de marzo y el 27 de abril de 2020. Se recogieron variables demográficas (edad, sexo, institucionalización), clínicas (síntomas, comorbilidades, índice de Charlson) y analíticas (bioquímica en suero, gasometría, hematimetría, hemostasia). Se derivó un modelo de riesgo y se compararon las escalas de gravedad PSI, CURB-65 y SCAP para predecir la mortalidad intrahospitalaria por cualquier causa. RESULTADOS: Se incluyeron 186 pacientes, con una mediana de edad de 85 años (RIC 80-89), un 44,1% varones. La mortalidad fue del 47,3%. Las escalas PSI, CURB-65 y SCAP tuvieron un área bajo la curva (ABC) de 0,74 (IC 95% 0,64-0,82), 0,71 (IC 95% 0,62-0,79) y 0,72 (IC 95% 0,63-0,81), respectivamente. El modelo predictivo compuesto por la ausencia o presencia de síntomas (tos y disnea), comorbilidad (índice de Charlson) y datos analíticos (aspartato- aminotransferasa, potasio, urea y lactato-deshidrogenasa) tuvo un ABC de 0,81 (IC 95% 0,73-0,88). CONCLUSIONES: Este estudio muestra que la escala PSI tiene una capacidad predictiva de mortalidad moderada, notablemente mejor que las escalas CURB-65 y SCAP. Se propone un nuevo modelo predictivo de mortalidad que mejora significativamente el rendimiento de estas escalas, siendo necesario verificar su validez externa.

Cause-specific death in hospitalized individuals infected with SARS-CoV-2: more than just acute respiratory failure or thromboembolic events.

Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75-89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10-22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82, p < 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15-11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40-103.86), frailty (OR 8.73 95% CI 1.37-55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02-0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.