Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy,antiplatelet therapy and inflammation

BackgroundCoronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy.AimTo assess if platelet activation influences mortality in COVID-19.MethodsWe explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48 hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality.ResultsIn cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876–54,678) pg/mL; sCD40L 1914 (interquartile range 1410–2367) pg/mL (P < 0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P = 0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64–12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80–1.37; P = 0.73).ConclusionsAlthough we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.     

Association entre l’hypertension artérielle,les traitements inhibiteurs du système rénine angiotensine et les formes graves de COVID-19. Étude prospective monocentrique française

Background and aimAngiotensin converting enzyme (ACE) type 2 is the receptor of SARSCoV-2 for cell entry into lung cells. Because ACE-2 may be modulated by ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there are concern that patients treated with ACEIs and ARBs are at higher risk for COVID-19 infection or severity. This study sought to analyse the association of severe forms of COVID-19 and mortality with hypertension and a previous treatment with ACEI and ARB.MethodsProspective follow-up of 433 consecutive patients hospitalised for COVID-19 pneumonia confirmed by PCR or highly probable on clinical, biological, and radiological findings, and included in the COVHYP study. Mortality and severe COVID-19 (criteria: death, intensive care unit, or hospitalisation > 30 days) were compared in patients receiving or not ACEIs and ARBs. Follow-up was 100% at hospital discharge, and 96.5% at > 1 month.ResultsAge was 63.6 ± 18.7 years, and 40%) were female. At follow-up (mean 78 ± 50 days), 136 (31%) patients had severity criteria (death, 64 ; intensive care unit, 73; hospital stay > 30 days, 49). Hypertension (55.1% vs 36.7%, P < 0.001) and antihypertensive treatment were associated with severe COVID-19 and mortality. The association between ACEI/ARB treatment and COVID-19 severity criteria found in univariate analysis (Odds Ratio 1.74, 95%CI [1.14–2.64], P = 0.01) was not confirmed when adjusted on age, gender, and hypertension (adjusted OR1.13 [0.59–2.15], P = 0.72). Diabetes and hypothyroidism were associated with severe COVID-19, whereas history of asthma was not.ConclusionThis study suggests that previous treatment with ACEI and ARB is not associated with hospital mortality, 1- and 2-month mortality, and severity criteria in patients hospitalised for COVID-19. No protective effect of ACEIs and ARBs on severe pneumonia related to COVID-19 was demonstrated.     

Factores de riesgo de muerte hospitalaria en pacientes con infarto agudo de miocardio durante la pandemia de la COVID-19

Introduction and objectivesDespite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic.MethodsThis prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model.ResultsIn total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P < .001] and 15.2% vs 1.8% [P = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52–62.51; P = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P = .02) were independent predictors of in-hospital death.ConclusionsDuring this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.Full English text available from:www.revespcardiol.org/en     

Preadmission predictors of severe COVID-19 in patients with diabetes mellitus

ObjectiveTo explore predictors of severe COVID-19 disease in patients with diabetes hospitalized for COVID-19.MethodsThis is a retrospective observational study of adults with diabetes admitted for COVID-19. Bivariate tests and multivariable Cox regression were used to identify risk factors for severe COVID-19, defined as a composite endpoint of intensive care unit admission/intubation or in-hospital death.ResultsIn 1134 patients with diabetes admitted for COVID-19, more severe disease was associated with older age (HR 1.02, p < 0.001), male sex (HR 1.28, p = 0.017), Asian race (HR 1.34, p = 0.029 [reference: white]), and greater obesity (moderate obesity HR 1.59, p = 0.015; severe obesity HR 2.07, p = 0.002 [reference: normal body mass index]). Outpatient diabetes medications were not associated with outcomes.ConclusionsAge, male sex, Asian race, and obesity were associated with increased risk of severe COVID-19 disease in adults with type 2 diabetes hospitalized for COVID-19.SummaryIn patients with type 2 diabetes hospitalized for COVID-19 disease, we observed that age, male sex, Asian race, and obesity predicted severe COVID-19 outcomes of intensive care unit admission, intubation, or in-hospital death. The risk conferred by obesity increased with worsening obesity. Outpatient diabetes medications were not observed to be significant predictors of study outcomes.     

Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes

AimsTo describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity.MethodsDemographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed.ResultsSeventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4⁺ T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4⁺ T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979–0.997) and increased SAA levels (OR = 1.029, 95%CI 1.002–1.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05).ConclusionsType 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4⁺ T lymphocyte counts and high SAA levels.     

Acute kidney injury in hospitalized patients with COVID-19: A Portuguese cohort

IntroductionThe incidence of acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients ranges from 0.5% to 35% and has been associated with worse prognosis. The purpose of this study was to evaluate the incidence, severity, duration, risk factors and prognosis of AKI in hospitalized patients with COVID-19.MethodsWe conducted a retrospective single-center analysis of 192 hospitalized COVID-19 patients from March to May of 2020. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (SCr) criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions.ResultsIn this cohort of COVID-19 patients, 55.2% developed AKI (n = 106). The majority of AKI patients had persistent AKI (n = 64, 60.4%). Overall, in-hospital mortality was 18.2% (n = 35) and was higher in AKI patients (28.3% vs. 5.9%, p < 0.001, unadjusted OR 6.03 (2.22–16.37), p < 0.001). In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02–1.11), p = 0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60–0.98), p = 0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37–22.72), p = 0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32–5.33), p = 0.006) were independent predictors of mortality.ConclusionAKI was frequent in hospitalized patients with COVID-19. Persistent AKI and higher severity of AKI were independent predictors of in-hospital mortality.     

Impacto de los inhibidores de la enzima de conversión de la angiotensina y los antagonistas del receptor de la angiotensina II en la COVID-19 en una población occidental. Registro CARDIOVID

Introduction and objectivesCoronavirus disease (COVID-19) has been designated a global pandemic by the World Health Organization. It is unclear whether previous treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) affects the prognosis of COVID-19 patients. The aim of this study was to evaluate the clinical implications of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection.MethodsSingle-center, retrospective, observational cohort study based on all the inhabitants of our health area. Analyses of main outcomes (mortality, heart failure, hospitalization, intensive care unit [ICU] admission, and major acute cardiovascular events [a composite of mortality and heart failure]) were adjusted by multivariate logistic regression and propensity score matching models.ResultsOf the total population, 447 979 inhabitants, 965 patients (0.22%) were diagnosed with COVID-19 infection, and 210 (21.8%) were under ACEI or ARB treatment at the time of diagnosis. Treatment with ACEI/ARB (combined and individually) had no effect on mortality (OR, 0.62; 95%CI, 0.17-2.26; P = .486), heart failure (OR, 1.37; 95%CI, 0.39-4.77; P = .622), hospitalization rate (OR, 0.85; 95%CI, 0.45-1.64; P = .638), ICU admission (OR, 0.87; 95%CI, 0.30-2.50; P = .798), or major acute cardiovascular events (OR, 1.06; 95%CI, 0.39-2.83; P = .915). This neutral effect remained in a subgroup analysis of patients requiring hospitalization.ConclusionsPrevious treatment with ACEI/ARB in patients with COVID-19 had no effect on mortality, heart failure, requirement for hospitalization, or ICU admission. Withdrawal of ACEI/ARB in patients testing positive for COVID-19 would not be justified, in line with current recommendations of scientific societies and government agencies.     

Clinical and Epidemiological Correlates of Low IFN-Gamma Responses in Mitogen Tube of QuantiFERON Assay in Tuberculosis Infection Screening During the COVID-19 Pandemic: A Population-Based Marker of COVID-19 Mortality?

BackgroundThe clinical and epidemiological implications of abnormal immune responses in COVID-19 for latent tuberculosis infection (LTBI) screening are unclear.MethodsWe reviewed QuantiFERON TB Gold Plus (QFT-Plus) results (36,709 patients) from July 2016 until October 2021 in Asturias (Spain). We also studied a cohort of ninety hospitalized patients with suspected/confirmed COVID-19 pneumonia and a group of elderly hospitalized patients with COVID-19 who underwent serial QFT-Plus and immune profiling testing.ResultsThe indeterminate QFT-Plus results rate went from 1.4% (July 2016 to November 2019) to 4.2% during the COVID-19 pandemic. The evolution of the number of cases with low/very low interferon-gamma (IFN-gamma) response in the mitogen tube paralleled the disease activity and number of deaths during the pandemic waves in our region (from March 2020 to October 2021). The percentages of positive QFT-plus patients did not significantly change before and during the pandemic (13.9% vs. 12.2%). Forty-nine patients from the suspected/confirmed COVID-19 pneumonia cohort (54.4%) had low/very low IFN-gamma response to mitogen, 22 of them (24.4%) had severe and critical pneumonia. None received immunosuppressants prior to testing. Abnormal radiological findings (P = 0.01) but not COVID-19 severity was associated with low mitogen response. Immune profiling showed a reduction of CD8 + T cells and a direct correlation between the number of EMRA CD8 + T-cells and IFN-gamma response to mitogen (P = 0.03).ConclusionLow IFN-gamma responses in mitogen tube of QFT-Plus often occur in COVID-19 pneumonia, which is associated with a low number of an effector CD8 + T-cell subset and does not seem to affect LTBI screening; however, this abnormality seems to parallel the dynamics of COVID-19 at the population level and its mortality.     

Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality

IntroductionSome COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood.ObjectiveTo study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients.MethodsFrom May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins.ResultsA total of 97 patients were included; mean age = 59.9 ± 16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality = 45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p < 0.001) for the cut-off of 1873.0 ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI = 1.8–59.5; p = 0.008) and ferritin ≥1873.0 ng/mL had an OR of 6.0 (95% CI = 1.4–26.2; p = 0.016), both independently associated with mortality based on logistic regression analysis.ConclusionThe magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.     

Impacto de la COVID-19 en el tratamiento del infarto agudo de miocardio con elevación del segmento ST. La experiencia española

Introduction and objectivesThe COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak.MethodsUsing a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19.ResultsSuspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P < .001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P < .001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P = .017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization.ConclusionsThe number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.     

Lung Function,Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge

IntroductionImpairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia.MethodsCOVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits.ResultsIn total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001).ConclusionAlmost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.     

Machine learning-based scoring system to predict in-hospital outcomes in patients hospitalized with COVID-19

BackgroundThe evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic.AimsTo develop and validate a score to predict outcomes in patients hospitalized with COVID-19.MethodsAll consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort.ResultsAmong 2873 patients analysed (57.9% men; 66.6 ± 17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n = 2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75–0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores.ConclusionsThe CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources.     

The effect of liver test abnormalities on the prognosis of COVID-19

IntroductionCOVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality.Materials and methodsOur study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course.ResultsMean age of 554 subjects were 66.21 ± 15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2 ± 33.6 U/L), ALT (34.01 ± 49.34 U/L), ALP (78.8 ± 46.86 U/L), GGT (46.25 ± 60.05 U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT–AST levels during their admission to the hospital (p = 0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC = 0.713: p = 0.001) and expected probability of intensive care unit admission (AUC = 0.636: p = 0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001).ConclusionsALT–AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.     

Identification of Pleural Response Patterns: A Cluster Analysis

BackgroundPleural effusion occurs as a response of the pleura to aggressions. The pleura reacts differently according to the type of injury. However, pleural reactions have not yet been characterized. The objective of this study was to identify homogeneous clusters of patients based on the analytical characteristics of their pleural fluid and identify pleural response patterns.MethodsA prospective study was conducted of consecutive patients seen in our unit for pleural effusion. Principal component and cluster analyses were carried out to identify pleural response patterns based on a combination of pleural fluid biomarkers.ResultsA total of 1613 patients were grouped into six clusters, namely: cluster 1 (10.5% of the cohort, primarily composed of patients with malignant pleural effusions); cluster 2 (17.4%, pleural effusions with inflammatory biomarkers); cluster 3 (16.1%, primarily composed of patients with infectious pleural effusions); cluster 4 (2.5%, a subcluster of cluster 3, superinfectious effusions); cluster 5 (23.4%, paucicellular pleural effusions); and cluster 6 (30.1%, miscellaneous). Significant differences were observed across clusters in terms of the analytical characteristics of PF (p < 0.001 for all), age (p < 0.001), and gender (p = 0.016). A direct relationship was found between the type of cluster and the etiology of pleural effusion.ConclusionPleural response is heterogeneous. The pleura may respond differently to the same etiology or similarly to different etiologies, which hinders diagnosis of pleural effusion.     

Increase in COVID-19 inpatient survival following detection of Thromboembolic and Cytokine storm risk from the point of admission to hospital by a near real time Traffic-light System (TraCe-Tic)

IntroductionOur goal was to evaluate if traffic-light driven personalized care for COVID-19 was associated with improved survival in acute hospital settings.MethodsDischarge outcomes were evaluated before and after prospective implementation of a real-time dashboard with feedback to ward-based clinicians. Thromboembolism categories were “medium-risk” (D-dimer >1000 ng/mL or CRP >200 mg/L); “high-risk” (D-dimer >3000 ng/mL or CRP >250 mg/L) or “suspected” (D-dimer >5000 ng/mL). Cytokine storm risk was categorized by ferritin.Results939/1039 COVID-19 positive patients (median age 67 years, 563/939 (60%) male) completed hospital encounters to death or discharge by 21st May 2020. Thromboembolism flag criteria were reached by 568/939 (60.5%), including 238/275 (86.6%) of the patients who died, and 330/664 (49.7%) of the patients who survived to discharge, p < 0.0001. Cytokine storm flag criteria were reached by 212 (22.6%) of admissions, including 80/275 (29.1%) of the patients who died, and 132/664 (19.9%) of the patients who survived, p < 0.0001. The maximum thromboembolism flag discriminated completed encounter mortality (no flag: 37/371 [9.97%] died; medium-risk: 68/239 [28.5%]; high-risk: 105/205 [51.2%]; and suspected thromboembolism: 65/124 [52.4%], p < 0.0001). Flag criteria were reached by 535 consecutive COVID-19 positive patients whose hospital encounter completed before traffic-light introduction: 173/535 (32.3% [95% confidence intervals 28.0, 36.0]) died. For the 200 consecutive admissions after implementation of real-time traffic light flags, 46/200 (23.0% [95% confidence intervals 17.1, 28.9]) died, p = 0.013. Adjusted for age and sex, the probability of death was 0.33 (95% confidence intervals 0.30, 0.37) before traffic light implementation, 0.22 (0.17, 0.27) after implementation, p < 0.001. In subgroup analyses, older patients, males, and patients with hypertension (p ≤ 0.01), and/or diabetes (p = 0.05) derived the greatest benefit from admission under the traffic light system.ConclusionPersonalized early interventions were associated with a 33% reduction in early mortality. We suggest benefit predominantly resulted from early triggers to review/enhance anticoagulation management, without exposing lower-risk patients to potential risks of full anticoagulation therapy.     

Pacientes críticos COVID-19. ¿Han variado el manejo y los resultados en la UCI tras un año de pandemia? Estudio multicéntrico,prospectivo, observacional

ObjectiveTo compare the clinical characteristics, treatments, and evolution of critical patients with COVID-19 pneumonia treated in intensive care units (ICU) after one year of pandemic.MethodologyMulticenter, prospective study, which included critical COVID-19 patients in 9 ICUs in northwestern Spain. The clinical characteristics, treatments, and evolution of patients admitted to the ICU during the months of March-April 2020 (period 1) were compared with patients admitted in January-February 2021 (period 2).Results337 patients were included (98 in period 1 and 239 in period 2). In period 2, fewer patients required invasive mechanical ventilation (IMV) (65% vs. 84%, P < .001), using high-flow nasal cannulas (CNAF) more frequently (70% vs. 7%, P < .001), ventilation non-invasive mechanical (NIMV) (40% vs. 14%, P < .001), corticosteroids (100% vs. 96%, P = .007) and prone position in both awake (42% vs. 28%, P = .012), and intubated patients (67% vs. 54%, P = .034). The days of IMV, ICU stay and hospital stay were lower in period 2. Mortality was similar in the two periods studied (16% vs. 17%).ConclusionsAfter one year of pandemic, we observed that in patients admitted to the ICU, CNAF, NIMV, use of the prone position, and corticosteroids have been used more frequently, reducing the number of patients in IMV, and the length of stay in the ICU and hospital stay. Mortality was similar in the two study periods.     

Ventilatory Support Use in Hospitalized Patients With Community-Acquired Pneumonia. Fifteen-year Trends in Spain (2001–2015)

AimWe examined fifteen years trends (2001–2015) in the use of non-invasive ventilation (NIV), invasive mechanical ventilation (IMV) or both (NIV + IMV) among patients hospitalized for community acquired pneumonia (CAP). We also analyzed trends overtime and the influence of patient factors in the in-hospital mortality (IHM) after receiving NIV, IMV or NIV + IMV.MethodsObservational retrospective epidemiological study. Our data source was the Spanish National Hospital Discharge Database.ResultsOver a total of 1,486,240 hospitalized patients with CAP, we identified 56,158 who had received ventilator support in Spain over the study period. Of them, 54.82% received NIV, 37.04% IMV and 8.14% both procedures. The use of NIV and NIV + IMV increased significantly (p < 0.001) over time (from 0.91 to 12.84 per 100.000 inhabitant and from 0.23 to 1.19 per 100.000 inhabitants, respectively), while the IMV utilization decreased (from 3.55 to 2.79 per 100,000 inhabitants; p < 0.001). Patients receiving NIV were the oldest and had the highest mean value in the Charlson comorbidity index (CCI) score and readmission rate. Patients who received only IMV had the highest IHM. Factors associated with IHM for all groups analyzed included age, comorbidities and readmission. IHM decreased significantly over time in patients with CAP who received NIV, IMV and NIV + IMV.ConclusionsWe found an increase in NIV use and a decline in IMV utilization in patients hospitalized for CAP over the study period. Patients receiving NIV were the oldest and had the highest CCI score and readmission rate. IHM decreased significantly over time in patients with CAP who received NIV, IMV and NIV + IMV.     

A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure

BackgroundHeart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM).Materials and methodsA total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA.ResultsLevels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p < 0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p < 0.0001, GDF-15 p = 0.0394, suPAR p = 0.0029, H-FABP p < 0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p < 0.0001) and diabetes (sST2 p = 0.0021, GDF-15 p = 0.0055, suPAR p = 0.0339, H-FABP p = 0.0010) were significantly associated with a rise in cardiac biomarkers.ConclusionNovel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.