ABSTRACT
Introducción: Los pacientes COVID-19 presentan una coagulopatía caracterizada por una elevada incidencia de complicaciones tromboembólicas. Ante la controversia existente sobre el manejo de la tromboprofilaxis, se llevó a cabo un estudio con el objetivo de analizar el efecto de las diferentes dosis de heparina de bajo peso molecular (HBPM) utilizadas en los pacientes críticos con COVID-19. Material y métodos: Se evaluaron datos del Reg-COVID19. Se compararon dos grupos de pacientes según la dosis de HBPM administrada: profilaxis y tratamiento. El objetivo primario fue determinar si había relación de la dosis de HBPM con la mortalidad. Los objetivos secundarios incluyeron la incidencia de eventos trombóticos y hemorrágicos, la duración de la estancia en UCI, la ventilación mecánica invasiva y parámetros trombóticos e inflamatorios. Resultados: Se analizaron datos de 720 pacientes, 258 en el grupo de profilaxis y 462 en el de tratamiento. La proteína C reactiva, la ventilación mecánica invasiva, y el tratamiento con tocilizumab o corticosteroides se relacionaron con la elección de la dosis de HBPM. La incidencia de complicaciones hemorrágicas (66/720, 9.2%) y trombóticas (69/720, 9.6%) fue similar en ambos grupos, al igual que el curso temporal de los eventos trombóticos, que ocurrieron antes que los hemorrágicos (9 [3-18] y 12 [6-19] días respectivamente). La mortalidad fue menor en el grupo de profilaxis (25.2% frente a 35.1%), pero al aplicar un modelo de ponderación de probabilidad inversa, no se encontraron diferencias entre los grupos. Conclusión: No se encontraron efectos beneficiosos ni perjudiciales relacionados con la administración de dosis profilácticas o terapéuticas de HBPM en pacientes críticos COVID-19, con una tasa similar de complicaciones hemorrágicas o trombóticas. A partir de estos resultados, consideramos que son necesarios más estudios para determinar el protocolo óptimo de tromboprofilaxis en estos pacientes.
ABSTRACT
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
Purpose: Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19. Methods: : We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding. Results: : Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days), and a reduction in ICU length of stay (mean difference: -8.2 days; 95% CI -12.7 to -3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64). Conclusions: The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
Background: To explore the incidence and characteristics of new-onset pain, its impact on quality of life (HRQoL), and to quantify the presence of mood disorders in critically ill COVID-19 survivors. Methods: This is a preliminary report of PAIN-COVID clinical trial (NCT04394169) presenting a descriptive analysis in critical ill COVID 19 survivors one month after hospital discharge. Pain was assed using the Brief Pain Inventory short form, Douleur Neuropathique 4 Questions test and Pain Catastrophizing Scale. Health related quality of life (HRQoL) was evaluated with EQoL-5D/5L and mood disorders with Hospital Anxiety and Depression test (HAD).Results: From May 27th to July 19th 2020, 203 patients were consecutively screened for eligibility and 65 were finally included in this analysis. In 33 (50.8%) patients a new-onset pain was reported: 18 (54.5%) reported clinically significant intense pain, 11 (33.3%) a positive screening for neuropathic pain, 3 (9.1%) clinically relevant pain catastrophizing thoughts, 29 (87.9%) pain in ≥2 body sites and 5 (15.2%) widespread pain. Median EQoL-5D/5L index value and visual analogue scale was 0.8 (IQR 0.57-0.87) and 70 (IQR 60-80) respectively. Pain intensity was negatively correlated both to the former (Spearman Rho: -0.546, p<0.001) and to the latter (Spearman Rho: -0.387, p=0.001). A HAD anxiety and depression value over 8 were obtained in 7 (10,8 %) and 5 (7,7%) of patients, respectively.Conclusion: The incidence of new-onset pain in critically ill COVID-19 survivors is high and it was associated with a lower HRQoL. Trial registration: NCT04394169. Registered 19 May 2020. https://clinicaltrials.gov/ct2/show/NCT04394169
Subject(s)
Anxiety Disorders , Pain , Mood Disorders , Depressive Disorder , COVID-19 , NeuralgiaABSTRACT
Purpose We aimed to describe the use of high-flow nasal oxygen (HFNO) in patients with COVID-19 acute respiratory failure and factors associated with a shift to invasive mechanical ventilation.Methods This is a multicentre, observational study from a prospectively collected database of consecutive COVID-19 patients admitted to 36 Spanish and Andorran intensive care units (ICUs) who received HFNO on ICU admission during a 22-week period (March 12-August 13, 2020). Outcomes of interest were factors on the day of ICU admission associated with the need for endotracheal intubation. We used multivariable logistic regression and mixed effects models. A predictive model for endotracheal intubation in patients treated with HFNO was derived and internally validated.Results From a total of 259 patients initially treated with HFNO, 140 patients (54%) required invasive mechanical ventilation. Baseline non-respiratory Sequential Organ Failure Assessment (SOFA) score [odds ratio (OR) 1.78; 95% confidence interval (CI) 1.41–2.35], and the ROX index calculated as the ratio of partial pressure of arterial oxygen to inspired oxygen fraction divided by respiratory rate (OR 0.53; 95% CI: 0.37–0.72), and pH (OR 0.47; 95% CI: 0.24–0.86) were associated with intubation. Hospital site explained 1% of the variability in the likelihood of intubation after initial treatment with HFNO. A predictive model including non-respiratory SOFA score and the ROX index showed excellent performance (AUC 0.88, 95%CI 0.80–0.96).Conclusions Among adult critically ill patients with COVID-19 initially treated with HFNO, the SOFA score and the ROX index may help to identify patients with higher likelihood of intubation.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
Background: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods Prospective, multicentre, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June, 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory sequential organ failure assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO+awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95%CI: 0.53–1.43), p=0.60]. Patients treated with HFNO+awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days, (p=0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95%CI: 0.40–2.72), p=0.92]. Conclusion In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.
Subject(s)
COVID-19 , Obesity , Respiratory InsufficiencyABSTRACT
Background: Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose. Methods: : This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from March 12 th to June 29 th , 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48h of ICU admission) with those who did not receive early corticosteroids or any corticosteroids at all. Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications. Results: : A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n=485) had a lower ICU mortality (30.3% vs 40.6%, HR 0.71, 95% CI 0.57-0.89) and higher number of ventilator-free days (mean difference 2.5 days, 95% CI 1.3-3.8) compared to non-early treated patients. There were no differences in 7-day mortality (HR 0.76, 95% CI 0.48-1.2), medical complications (OR 2.18, 95% CI 0.91-5.25) or secondary infections (OR 0.88, 95% CI 0.67-1.15) between both groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens. Conclusion: Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality (10.3% absolute risk reduction) and shorter duration of mechanical ventilation.
Subject(s)
Poult Enteritis Mortality Syndrome , Coronavirus Infections , COVID-19ABSTRACT
Background: Critically ill patients with COVID-19 disease are an especially susceptible population to develop Post-intensive Care Syndrome (PICS) due to acute respiratory distress syndrome (ARDS). Patients can suffer acute severe pain and may have long-term deterioration in mental, cognitive, and functional health after discharge. However, few controlled trials are evaluating interventions for the prevention and treatment of PICS. The study hypothesis is that a specific care program based on early therapeutic education and a psychological intervention improves the quality of life of patients at risk of developing PICS and chronic pain after COVID-19 disease. The primary objective is to determine if the program is superior to standard-of-care on health-related life quality at six months after hospital discharge. The secondary objectives are to determine if the intervention is superior to standard care, evaluating the health-related life quality, the incidence of chronic pain and the degree of functional limitation, the incidence of anxiety, depression, and post-traumatic stress syndrome at 3 and 6 months after hospital discharge.Methods: The PAINCOVID trial is a unicentric randomized, controlled, patient blinded superiority trial with two parallel groups. The primary endpoint is the health-related quality of life at six months after hospital discharge, and randomization will be performed with a 1:1 allocation. This paper details the methodology and statistical analysis plan of the trial and was submitted before outcome data were available.The sample size calculated is 84 patients, 42 for each arm. Estimating a loss of follow up of 20%, a sample size of 102 patients is necessary (51 each group). Discussion: This is the first randomized clinical trial assessing the effectiveness of an early care therapeutic education, and psychological intervention for the management of PICS and Chronic Pain after COVID-19. The intervention will serve as a sample of the need to implement early care programs on early stages, having an incalculable impact given the current scenario of the pandemic.Trial registration: This study is being in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board Comité Ético de Investigación Clínica del Hospital Clinic de Barcelona (approval number: HCB/2020/0549) and was registered on May 9, 2020 at clinicaltrials.gov (NCT04394169).