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Coronavirus Disease-19 (COVID-19), caused by SARS-CoV-2 infection, is associated with a rise in inflammatory markers which can result in altered coagulation system activation and regulation. During COVID-19, a remarkable tendency towards venous thrombosis and thrombo-embolism has been widely reported, especially in the critically ill patients. Thus, to limit this clinically relevant events, various strategies of venous thrombo-prophylaxis and anticoagulation have been studied. On the other hand, arterial thrombosis seems to play a less relevant role the clinical picture of COVID-19, as much as bleeding complications, which are mostly correlated to anticoagulation management. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Introduction: Diagnosis of ventilator-associated pneumonia (VAP) in COVID-19 patients remains challenging. Also, the lack of gold standard for microbiological sampling undermines clinical judgement and management. We studied incidences of microbiologically-confirmed VAP comparing endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) in COVID-19 patients. Etiological agreement between ETA and BAL was then assessed. Method(s): Single-center prospective cohort study (NCT04766983). Patients were enrolled within 48 h from intubation;surveillance ETA ( ETASURV) was performed twice weekly. ETA ( ETACX) and BAL ( BALCX) samples were collected upon VAP suspicion (Johanson's criteria). CDC definitions were used for microbiological confirmation. ETA-BAL agreement (interrater reliability and Cohen's kappa) and clinical/microbiological data were assessed for the first episodes of suspected VAP per patients. Result(s): Ninety intensive care (ICU) patients enrolled from 01/2021 to 05 06/2022, of which 26 females (28.9%);median age was 60 [52-66] years. In-ICU mortality was 30/90 (33.3%), median length of stay in survivors 19 (10-32) days. Fifty-three patients (58.9%) had >= 1 episode of suspected VAP after 6 [5;10] days from ICU admission. ETASURV were available in 52 cases, 2 [1;3] days before VAP suspect, and tested positive in 28 (53.8%). ETACX and BALCX resulted positive in 35 (66.0%) and 29 (54.7%) of episodes. Main microbiological results are displayed in Fig. 1, panel A. Etiological agreement between techniques is shown in Fig. 1, panel B. Incidence rate of VAP suspicions per 1000 ventilator-days was 60.2 (95% CI 43.9-76.4), while incidence rates of microbiologically-confirmed VAP were 27.4 (18.3-36.5) with ETACXand 18.9 (95% CI 12.0-25.8) with BALCX, respectively. Conclusion(s): We observed different incidence of VAP in COVID-19 ICU patients depending on sampling method. Etiological agreement between techniques yielded limited interrater reliability. The potential clinical impact needs further studies.
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Background: Hemorrhage, coagulopathy and thrombosis (HECTOR) are reported complications of coronavirus disease 2019 (COVID-19) however, more information is needed on the prevalence of these complications and their associated outcomes in intensive care unit (ICU) settings. Aim(s): To determine the prevalence and outcomes of HECTOR complications in ICU patients with COVID-19. Method(s): Observational cohort study spanning 229 ICUs across 32 countries. Patients >=16 years admitted for severe COVID-19 from 1st January 2020, through 31st December 2021 were included. Patient characteristics and clinical data were collected. Survival analysis estimated the instantaneous impact of HECTOR complications on ICU-mortality and discharge. Result(s): HECTOR complications occurred in 1,735 (14%) of 11,972 study-eligible patients. Acute thrombosis occurred in 1,249 (10%) patients, including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial infarction, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic stroke. Hemorrhagic complications were reported in 582 (4.9%) patients, including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, and 77 (13%) with pulmonary hemorrhage. Disseminated intravascular coagulation occurred in 11 (0.09%) patients. Univariate analysis identified diabetes, hypertension, cardiac and kidney disease and ECMO as statistically-significant risk factors for HECTOR complications. Patients with versus without HECTOR complications suffered higher ICU-mortality at 28 days (25%vs.13%, p < 0.001), 90 days (32%vs.15%, p < 0.0001) and overall (44%vs.36%, p < 0.001). Among ICU survivors, the ICU stay was longer (median days 19vs.12, p < 0.001). ICU mortality was similar between patients with and without HECTOR complications (HR = 1.01, 95%CI 0.92-1.12, p = 0.783) where an increased hazard of ICU mortality with hemorrhage (HR = 1.26, 1.09-1.45, p = 0.002) was balanced by a reduced hazard of thrombosis (HR = 0.88, 0.79-0.99, p = 0.03). Kaplan-Meier curves are presented in the Figure. Conclusion(s): HECTOR events are frequent complications of severe COVID-19 in ICU patients. Hemorrhagic, but not thrombotic complications are associated with increased ICU-mortality.
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Background : Covid-19 infection is associated with a widespread global activation of coagulation and affected patients are at an increased risk of thrombosis. Aims : Heparin therapy is effective in various setting in preventing thromboembolic complications and aim of this study was to assess heparin response in COVID-19 patients through anti-FXa test. Methods : In 52 patients, M:F ratio 59:41, median age 59 years old, admitted in different intensity of care units of our hospital, treated with different regimens of heparin (100 U/kg every 24 h in low intensity care, 70 U/kg every 12 h in intermediate intensity care and 100 U/kg every 12 h in intensive care unit), anti-FXa levels were measured immediately before and 3 h after subcutaneous enoxaparin administration. On the same samples thrombin generation tests were performed. Results : Patients treated with 100 U/kg every 24 h and 70 U/ kg every 12 h had median anti-FXa basal levels in the prophylactic range, respectively 0.18 and 0.22 U/ml, while patients treated with 100 U/kg every 12 h were in the anticoagulant range (0.37 U/ ml). Despite heparin therapy thrombin generation was elevated in COVID-19 patients, indicating a high level of coagulation activation. Conclusions : In conclusion we demonstrated that the biological response to enoxaparin in COVID-19 patients is in the expected range using anti-FXa assay and patients are not resistant to heparin therapy.
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Introduction: The AFTERCOR study was developed by the COVID-19 Critical Care Consortium (>7000 intensive care unit [ICU] and >400 extracorporeal membrane oxygenation [ECMO] patients currently) to enhance understanding of occurrence and progression of long-term dysfunction post-COVID-19. Design: Prospective longitudinal (24 months) study of ICU survivors of COVID-19 to describe recovery of the following aspects: a) health-related quality of life b) dynamics of organ dysfunction and recovery and c) pulmonary function. Countries involved Italy, Spain, Ireland, Austria, South Africa, Australia, USA, Argentina, Brazil, Colombia. Protocol specifics available at https://www.aftercorstudy.com. Inclusion Criteria: 1) COVID-19 infection requiring ICU admission;2) informed consent;3) age ≥18 years. Exclusion Criteria: 1) pregnancy;2) pre-COVID paralysis;3) history of pulmonary resection;4) prior lung transplant;5) inability to perform 6-min walk test or participate in interview. Methods: Goal enrollment is 1000 patients. Follow-up visits are at 3, 6, 12, 18 and 24-month post-ICU discharge. Assessments include: 1) Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36);2) Montreal Cognitive Assessment;3) any subsequent admission 4) St. George's Respiratory Questionnaire;5) Pulmonary function testing;6) chest radiography;7) 6-minute-walk test;8) Patient Health Questionnaire 9 (PHQ-9) and 9) full blood count and biochemistry. CT chest at 6 months and repeat ECHO at 3, 12 and 24 months if performed during COVID-19 hospitalization. If results are normal, subsequent testing will not be performed. Summary: The AFTERCOR study represents a comprehensive evaluation for long-term effects from COVID-19. Interested centers are sought and invited to participate.
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Introduction: The ClotPro system (enicor GmbH, Germany) is a novel rotational viscoelastic analyzer that assesses the coagulation cascade through different reagents. Russels Viper Venom (RVV) is a direct activator of fX to fXa, and it is mostly employed to monitor direct oral anticoagulants. IN test evaluates the intrinsic pathway of coagulation via ellagic acid addition. The ability of these tests to monitor heparin administration during veno-venous ECMO (vvECMO)-compared to the gold standard anti-Xa activity-is to be cleared. Objective: To evaluate the correlation of RVV and IN test clotting time (CT) with anti-Xa activity during unfractioned heparin (UFH) administration in vvECMO. Methods: Intensive care unit (ICU) patients undergoing vvECMO and continuous UFH administration were enrolled. Standard coagulation tests, anti-Xa activity, RVV and IN test were simultaneously conducted. Results: Eight patients were enrolled (September 2020-February 2021), for a total of 53 observations (5 [2-9] per patient). SARS-CoV2 infection was the main diagnosis (50%), followed by Legionella pneumonia, HSV pneumonia, bridge to lung transplantation and COPD relapse. Age was 54.0 [42.5-60.5] years old, body mass index was 26.6 [24.1-28.5] kg/m2. Prolongation of RVV and IN CT was observed in our cohort (see Table 1 for the main study findings), and it was found to be strongly correlated to plasma anti-Xa activity (Figures 1, 2). Conclusions: RVV and IN test clotting time at ClotPro system might be used for anti-coagulation monitoring during vvECMO and UFH administration. Further studies are needed for clinical translatability of these findings.
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Rationale Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous smallcase series or studies conducted at a national level.Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe the impact of CRS on the ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.Results We enrolled 318 COVID-19 patients enrolled into the study from January 14th through September 31th, 2020 in 19 countries and stratified into two CRS groups. CRS was calculated as: tidal volume/[airway plateau pressure-positive endexpiratory pressure (PEEP)] and available within 48h from commencement of MV in 318 patients. Patients were mean±SD of 58.0±12.2, predominantly from Europe (54%) and males (68%). Median CRS (IQR) was 34.1 mL/cmH2O (26.5-45.5) and PaO2/FiO2 was 119 mmHg (87.1-164) and was not correlated with CRS. Female sex presented lower CRS than in males (95% CI:-13.8 to-8.5 P<0.001) and higher body mass index (34.7±10.9 vs 29.1±6.0, p<0.001). Median (IQR) PEEP was 12 cmH2O (10-15), throughout the range of CRS, while median (IQR) driving pressure was 12.3 (10-15) cmH2O and significantly decreased as CRS improved (p<0.001). No differences were found in comorbidities and clinical management between CRS strata. In addition, 28-day ICU mortality and hospital mortality did not differ between CRSgroups.Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV-predominantly males or overweight females, in their late 50s-admitted to ICU during the first international outbreaks. Phenotypes associated with different CRS upon commencement of MV could not be identified.
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Background: Viscoelastic Coagulation Monitor (VCM-Entegrion, Durham, NC) is a portable, recently validated device developed to quickly evaluate the viscoelastic properties of whole blood activated by direct contact with a glass surface. We employed VCM as daily assessment of COVID-19 critically ill patients. Aim of the study was to assess whether VCM parameters were modified by heparin administration. Methods: Retrospective cohort study on COVID-19 critically ill patients who were tested with VCM during their ICU stay from March 25th to June 8th. Anticoagulation was provided either with unfractionated (UFH) or with low molecular weight (LMWH) heparin, per institutional protocol. VCM analysis was simultaneously run to standard coagulation tests Results: Thirty-six patients were included in the study for a total of 151 measurements. ECMO patients (N=4) received UFH, the remaining (except one that was heparin-free) received LMWH, for a total of 52 samples on UFH, 86 samples on LMWH, and 13 samples without any anticoagulant. The administration of UFH influenced VCM parameters towards hypocoagulability whereas LMWH did not. No flat-line tracings were observed. The correlation between VCM Clotting Time and UFH dose was moderate (Spearman's rho = 0.48, p = <0.001), the correlation between aPTT and UFH was weak (Spearman's rho = 0.35, p = 0.010). As expected, no correlation was found between VCM parameters and LMWH dose. Conclusions: VCM parameters were modified only by anticoagulant doses of UFH in a cohort of COVID-19 critically ill patients. VCM could be further evaluated as a tool for UFH anticoagulation monitoring.