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Mansor NF, Abdul Halim Zaki I, Kiok LC, Seng EK, Ravi T, Pathmanathan M, Goh KW, Ming LC, Razi P, Zulkifly HH. The prevalence of thromboembolic events among COVID-19 patients admitted to a single centre intensive care unit (ICU): an epidemiological study from a Malaysian population. J Pharm Policy Pract 2025; 18:2449044. [PMID: 39917475 PMCID: PMC11800336 DOI: 10.1080/20523211.2024.2449044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 12/28/2024] [Indexed: 02/09/2025] Open
Abstract
Introduction Thromboembolic (TE) complications in COVID-19 patients are rising globally, contributing significantly to mortality, particularly in severe cases. However, their prevalence, characteristics, and impact on mortality in Malaysia remain unclear. Objectives This study aimed to determine the prevalence of thromboembolic (TE) events and associated mortality among COVID-19 patients admitted within a single centre intensive care unit (ICU). The proportions of patients with TE events who died, and factors associated with TE events were explored. Methods In this retrospective cohort study, patients with PCR confirmed SARS-CoV-2 virus and who received thromboprophylaxis within February 2020-2021 were included. TE event is a combination of venous [(deep vein thrombosis (DVT), pulmonary embolism (PE)] and arterial (myocardial infarction (MI), stroke) thromboembolism. Results Mean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU stay, 64.2%, 53.2% and 20.9% had underlying hypertension, diabetes and obesity respectively. In total, 240 (44.9%) developed TE event. Significantly higher proportions of COVID-19 patients who developed complications of DVT (2.5% vs. 0.2%; p = 0.013), PE (47.5% vs 34.0%; p = 0.006), stroke (12.3% vs. 1.5; p<0.001) and MI (16.4% vs. 4.6%; p<0.001) died. Predictors of TE events were age [HR 1.01 (95% CI 1.00-1.02)], obesity [HR 1.98 (95% CI 1.51-2.6)], D-dimer [HR 1.01 (95% CI 1.00-1.01)], and duration of ICU stay [HR 0.98 (95% CI 0.97-0.99)]. Conclusion In severely ill COVID-19 patients, TE complications were common, and patients with DVT, PE, stroke, or MI faced increased mortality, even with thromboprophylaxis. Age, obesity, elevated D-Dimer levels, and longer ICU stays were significant predictors of TE events. Considering these findings, a more aggressive approach, combining thromboprophylaxis with enhanced anti-inflammatory treatments, may be necessary for high-risk COVID-19 ICU patients to reduce TE events and mortality.
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Affiliation(s)
| | - Izzati Abdul Halim Zaki
- Faculty of Pharmacy, Universiti Teknologi MARA, UiTM Kampus Puncak Alam, Puncak Alam, Malaysia
- Cardiology Therapeutics Research Group, Universiti Teknologi MARA, UiTM Kampus Puncak Alam, Puncak Alam, Malaysia
| | - Lee Chew Kiok
- Anesthesiology and Intensive Care Department, Sungai Buloh Hospital, Sungai Buloh, Malaysia
| | - Eng Kar Seng
- Anesthesiology and Intensive Care Department, Sungai Buloh Hospital, Sungai Buloh, Malaysia
| | - Tharmini Ravi
- Clinical Research Center, Sungai Buloh Hospital, Sungai Buloh, Malaysia
| | - Mohan Pathmanathan
- Institute for Clinical Research, National Institutes of Health, Shah Alam, Malaysia
| | - Khang Wen Goh
- Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia
| | - Long Chiau Ming
- School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia
- Datta Meghe College of Pharmacy, Datta Meghe Institute of Higher Education and Research (deemed to be University), Sawangi (M), Wardha, India
| | - Pakhrur Razi
- Center of Disaster Monitoring and Earth Observation, Physics Department, Universitas Negeri Padang, Padang, Indonesia
| | - Hanis Hanum Zulkifly
- Faculty of Pharmacy, Universiti Teknologi MARA, UiTM Kampus Puncak Alam, Puncak Alam, Malaysia
- Cardiology Therapeutics Research Group, Universiti Teknologi MARA, UiTM Kampus Puncak Alam, Puncak Alam, Malaysia
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Balmakov Y, Mark T, Barnett I, Cipok M, Lev EI, Cohen A, Aviram E, Mayo A. Immature Platelets and Platelet Reactivity in Patients with COVID-19. Clin Appl Thromb Hemost 2025; 31:10760296251318320. [PMID: 39943824 PMCID: PMC11826839 DOI: 10.1177/10760296251318320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/16/2025] [Accepted: 01/20/2025] [Indexed: 02/16/2025] Open
Abstract
Coronavirus disease 2019 (COVID-19) is associated with a high incidence of thromboembolic events, both venous and arterial. There are currently no specific clinical or laboratory markers to guide antithrombotic therapy for COVID-19 patients. Immature platelets represent a population of hyper-reactive platelets associated with arterial thrombotic events. This prospective study compared consecutive severe COVID-19 patients (n = 53, median age = 73 years) versus patients with sepsis from another origin (n = 41, median age = 69 years). Total platelet counts, immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPC levels three days after admission were significantly higher in the COVID-19 group compared to the sepsis group (13.4 × 109/ L [IQR 9.1-18.5] in the COVID-19 group vs 9 × 109/ L [5.5-14.7] in the sepsis group, P = 0.007). COVID-19 patients with respiratory disease show increased platelet turnover and reactivity, as seen in higher levels of immature platelet indices, especially IPC, compared to the sepsis control group. While these platelet indices remained high, CRP levels decreased, particularly in patients treated with tocilizumab. This reduction in CRP was not accompanied by any apparent clinical improvement. These findings suggest that immature platelets may serve as a biomarker for disease severity in COVID-19 patients and their CRP may not be a reliable marker for disease severity.
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Affiliation(s)
- Yulia Balmakov
- Department of Military Medicine and “Tzameret”, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel, and Medical Corps, Israel Defense Forces, Jerusalem, Israel
| | - Tomer Mark
- Intensive Care Department, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, Ashdod, Israel
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
| | - Itzik Barnett
- Intensive Care Department, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, Ashdod, Israel
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
| | - Michal Cipok
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
- Laboratory Division, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, Ashdod, Israel
| | - Eli I. Lev
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
- Cardiology Department, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, 7 Harefua St, Ashdod, Israel
| | - Amir Cohen
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
- Cardiology Department, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, 7 Harefua St, Ashdod, Israel
| | - Eliad Aviram
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
| | - Ami Mayo
- Intensive Care Department, Assuta Ashdod Medical Center, The Faculty of Health Sciences, Ben-Gurion University, Ashdod, Israel
- Samson Assuta Ashdod Hospital, Ashdod, Israel; Faculty of Medicine,
Ben-Gurion University of the Negev, Be’er Sheva, Israel
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Sennary HA, Abozaid G, Hemeida A, Mikhaylov A. Detection of hate: speech tweets based convolutional neural network and machine learning algorithms. Sci Rep 2024; 14:28870. [PMID: 39572576 PMCID: PMC11582668 DOI: 10.1038/s41598-024-76632-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 10/15/2024] [Indexed: 11/24/2024] Open
Abstract
There is no doubt that social media sites have provided many benefits to humanity, such as sharing information continuously and communicating with others easily. It also seems that social media sites have many advantages, but in addition to these advantages, there are disadvantages that we always strive to find a solution. One of these disadvantages is sharing hate speech. In our study, we're discussing a way to solve this phenomenon by using Term Frequency-Inverse Document Frequency (TF-IDF) based approach to feature engineering on eleven classifiers for machine and deep learning that can automatically identify hate speech. Three different databases were used, the first of which "Hate speech offensive tweets by Davidson et al.", the second called "Twitter hate speech" and finally we merged the second data with (Cyberbullying dataset (toxicity_parsed_dataset)". The classifiers involved are Logistic Regression (LR), Naive Bayes (NB), Multi-layer Perceptron (MLP), and Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor (KNN), K-Means, Decision Tree (DT), Gradient Boosting classifier (GBC), and the Extra Trees (ET) in addition to the convolutional neural network (CNN). Maximum accuracy was attained, which exceeded 99%.
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Affiliation(s)
- Hameda A Sennary
- Department of Mathematics, Faculty of Science, Aswan University, Aswân, Egypt
| | - Ghada Abozaid
- Electrical Engineering Department, Faculty of Energy Engineering, Aswan University, Aswân, Egypt
| | - Ashraf Hemeida
- Electrical Engineering Department, Faculty of Energy Engineering, Aswan University, Aswân, Egypt.
| | - Alexey Mikhaylov
- Department of Financial Technologies, Financial University Under the Government of the Russian Federation, Moscow, 125993, Russia
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Almskog LM, Sjöström A, Sundén-Cullberg J, Taxiarchis A, Ågren A, Freyland S, Börjesson M, Wikman A, Wahlgren CM, Wanecek M, van der Linden J, Antovic J, Lampa J, Magnusson M. Tocilizumab reduces hypercoagulation in COVID-19 - Perspectives from the coagulation and immunomodulation Covid assessment (Coag-ImmCovA) clinical trial. Thromb Res 2024; 243:109135. [PMID: 39226747 DOI: 10.1016/j.thromres.2024.109135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood. METHODS In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests. RESULTS The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time. CONCLUSION Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.
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Affiliation(s)
- Lou M Almskog
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
| | - Anna Sjöström
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
| | - Jonas Sundén-Cullberg
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden
| | - Apostolos Taxiarchis
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Ågren
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden; Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden
| | - Sara Freyland
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Madeleine Börjesson
- Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden
| | - Agneta Wikman
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Stockholm, Sweden
| | - Carl Magnus Wahlgren
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Michael Wanecek
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Intensive Care Unit, Capio St Göran's Hospital, Stockholm, Sweden
| | - Jan van der Linden
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Jovan Antovic
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
| | - Jon Lampa
- Rheumatology Division, Department of Medicine Solna, Center for Molecular Medicine (CMM), Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Maria Magnusson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
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Dunton J, Bierman-Macke K, Little T, Zuk N, Beyersdorfer N, Goade S, Johnson K, Stahl G, Arnce RD. A Retrospective Analysis of Thrombosis and COVID-19 Mortality in Rural Midwestern Population. Cureus 2024; 16:e74320. [PMID: 39717294 PMCID: PMC11666284 DOI: 10.7759/cureus.74320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2024] [Indexed: 12/25/2024] Open
Abstract
Background COVID-19 disease has caused a major global impact on health and mortality. This infection may predispose patients to thrombotic disease, caused by excessive inflammation, endothelial dysfunction, platelet activation, and stasis. In this study, we compared mortality rates in patients admitted to the hospital with the diagnosis of COVID-19, who also had the additional diagnosis of thrombosis with those who did not have thrombosis as an additional diagnosis. Methods This retrospective observational study compared mortality rates in patients admitted to the hospital with the diagnosis of COVID-19, with and without thrombosis, as well as those patients admitted to the hospital with the diagnosis of thrombosis who did not have COVID-19. The diagnoses were verified using International Classification of Diseases Tenth Revision (ICD-10) codes, a standard among electronic medical records (EMR). The data were taken from the EMR at Freeman Health System in Joplin and Neosho, Missouri, from April 2020 to December 2021. This patient population is representative of not only Southwest Missouri but also the four-state area, including Oklahoma, Arkansas, and Kansas. The ICD-10 codes were used to separate the patient population into three main groups as follows: patients diagnosed with COVID-19 without thrombosis, patients diagnosed with thrombosis without COVID-19, and patients diagnosed with both COVID-19 and thrombosis. These three categories were then subdivided by age and biological sex. Sample proportions were completed using Wald's method, and the two-sample proportion summary hypothesis test with confidence intervals was used for the proportion difference. Results A total of 3,094 patients were included in the study population. Excluded from the study were patients who were previously admitted to a hospital for COVID-19 and duplicate admissions. The mortality rate was highest (0.4714) in patients concurrently diagnosed with COVID-19 and thrombosis (Population 1 {P1}), followed by patients diagnosed with COVID-19 without thrombosis (Population 2 {P2}, 0.1187). Patients diagnosed with thrombosis without COVID-19 (Population 3 {P3}, 0.1216) had the lowest mortality. Two sample proportion hypothesis tests determined confidence intervals (CI) for mortality risk comparing P3 to P1 (95% CI: 0.2888-0.4108, p<0.0001) and P2 to P1 (95% CI: 0.2919-0.4135, p<0.0001). Discussion In this rural, Midwestern population, patients admitted to the hospital with the diagnosis of COVID-19 and thrombosis had significantly increased mortality rates compared to patients admitted with the diagnosis of COVID-19 or thrombosis alone. Conclusion The data from this study indicated that individuals diagnosed with both COVID-19 and thrombosis had a higher likelihood of mortality compared to those diagnosed with COVID-19 without thrombosis and those diagnosed with thrombosis without COVID-19. This information could assist physicians in determining treatment plans for patients diagnosed with COVID-19 and a secondary complication of thrombosis.
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Affiliation(s)
- John Dunton
- Emergency Medicine, Kansas City University, Kansas City, USA
| | | | - Taylor Little
- Emergency Medicine, Kansas City University, Kansas City, USA
| | - Nicholas Zuk
- Emergency Medicine, Kansas City University, Kansas City, USA
| | | | - Scott Goade
- Clinical Pharmacy, Freeman Health System, Joplin, USA
- College of Medicine, Kansas City University, Joplin, USA
| | - Kerry Johnson
- Mathematics, Missouri Southern State University, Joplin, USA
| | - Greg Stahl
- Statistics, Freeman Health System, Joplin, USA
| | - Robert D Arnce
- College of Osteopathic Medicine, Kansas City University of Medicine and Biosciences, Joplin, USA
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Salas JR, Jacob C, Ibekwe E, Zakeri AS, Nimjee SM, Strohm T. ROTEM and von Willebrand Factor in COVID patients presenting with acute ischemic stroke: A case series: ROTEM and von Willebrand Factor in COVID-19 Related Stroke. J Stroke Cerebrovasc Dis 2024; 33:107894. [PMID: 39106921 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/09/2024] Open
Abstract
OBJECTIVES SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data. MATERIALS AND METHODS Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system. RESULTS Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA. CONCLUSIONS Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.
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Affiliation(s)
- Jesus R Salas
- Department of Neurology, The Ohio State University, Columbus, OH, USA
| | - Connor Jacob
- The Ohio State University College of Medicine, The Ohio State University, Columbus, OH, USA
| | | | - Amanda S Zakeri
- Department of Neurological Surgery, The Ohio State University, Columbus, OH, USA
| | - Shahid M Nimjee
- Department of Neurological Surgery, The Ohio State University, Columbus, OH, USA
| | - Tamara Strohm
- Department of Neurology, Division of Neurocritical Care, University of North Carolina, Chapel Hill, NC, USA.
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Babkina AS, Pisarev MV, Grechko AV, Golubev AM. Arterial Thrombosis in Acute Respiratory Infections: An Underestimated but Clinically Relevant Problem. J Clin Med 2024; 13:6007. [PMID: 39408067 PMCID: PMC11477565 DOI: 10.3390/jcm13196007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 10/07/2024] [Accepted: 10/07/2024] [Indexed: 10/20/2024] Open
Abstract
During the COVID-19 pandemic, there was increased interest in the issue of thrombotic complications of acute respiratory infections. Clinical reports and pathological studies have revealed that thrombus formation in COVID-19 may involve the venous and arterial vasculature. As thrombotic complications of infectious respiratory diseases are increasingly considered in the context of COVID-19, the fact that thrombosis in lung diseases of viral and bacterial etiology was described long before the pandemic is overlooked. Pre-pandemic studies show that bacterial and viral respiratory infections are associated with an increased risk of thrombotic complications such as myocardial infarction, ischemic stroke, pulmonary embolism, and other critical illnesses caused by arterial and venous thrombosis. This narrative review article aims to summarize the current evidence regarding thrombotic complications and their pathogenesis in acute lower respiratory tract infections.
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Affiliation(s)
- Anastasiya S. Babkina
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia; (M.V.P.); (A.V.G.); (A.M.G.)
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Raj K, Majeed H, Chandna S, Chitkara A, Sheikh AB, Kumar A, Gangu K, Pillai KJ, Agrawal A, Sadashiv SK, Kalra A. Increased risk of pulmonary embolism and deep vein thrombosis with COVID-19 pneumonia in comparison to influenza pneumonia: insights from the National Inpatient Sample database. J Thorac Dis 2024; 16:6161-6170. [PMID: 39444888 PMCID: PMC11494551 DOI: 10.21037/jtd-23-1674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 08/02/2024] [Indexed: 10/25/2024]
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily a respiratory virus causing coronavirus disease 2019 (COVID-19) pneumonia, induces a hypercoagulable state. Previous studies comparing the prevalence of venous thromboembolism (VTE) in patients with COVID-19 pneumonia and those with influenza pneumonia revealed a higher risk of pulmonary embolism (PE) and deep vein thrombosis (DVT) associated with COVID-19 pneumonia. However, these studies have not adequately accounted for the severity and acuity of the presenting viral pneumonia. Methods In this retrospective study, we rigorously adjusted for critical illness using a nationally representative dataset to investigate whether COVID-19 pneumonia is independently linked to a higher risk of PE and DVT. Results After comprehensive multivariate adjustment, our findings demonstrated that patients with COVID-19 pneumonia maintained significantly higher odds of developing acute inpatient PE [adjusted odds ratio (aOR): 2.48; 95% confidence interval (CI): 2.16-2.86; P<0.01] and DVT (aOR: 1.66; 95% CI: 1.41-1.96; P<0.01) during the early pandemic compared to patients with influenza pneumonia. Furthermore, we identified congenital heart disease and malnutrition as novel risk factors for acute PE in COVID-19 patients. Conclusions Our study suggests that the higher prevalence of acute inpatient PE over DVT in patients with COVID-19 pneumonia may support a "thrombus in situ" mechanism of SARS-CoV-2-mediated pulmonary thrombosis. Consequently, clinicians should maintain a high index of suspicion for PE, even in the absence of DVT, among patients with COVID-19 pneumonia and should follow evidence-based guidelines for diagnosis and management.
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Affiliation(s)
- Kavin Raj
- Department of Cardiology, University of California Riverside School of Medicine, Riverside, CA, USA
| | - Harris Majeed
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Sanya Chandna
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Akshit Chitkara
- Department of Cardiology, University of California Riverside School of Medicine, Riverside, CA, USA
| | - Abu Baker Sheikh
- Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
| | - Ashish Kumar
- Department of Internal Medicine, Cleveland Clinic Akron General, Cleveland, OH, USA
| | - Karthik Gangu
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | | | - Ankit Agrawal
- Department of Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Santhosh K. Sadashiv
- Department of Hematology and Oncology, West Penn Hospital, Alleghany Health Network, Pittsburgh, PA, USA
| | - Ankur Kalra
- Department of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA
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Desai R, Mellacheruvu SP, Akella SA, Mohammed AS, Hussain M, Mohammed AA, Saketha P, Sunkara P, Gummadi J, Ghantasala P. Recurrent stroke admissions with vs without COVID-19 and associated in-hospital mortality: A United States nationwide analysis, 2020. World J Virol 2024; 13:96453. [PMID: 39323442 PMCID: PMC11401001 DOI: 10.5501/wjv.v13.i3.96453] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 06/12/2024] [Accepted: 07/10/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has been shown to increase the risk of stroke. However, the prevalence and risk of recurrent stroke in COVID-19 patients with prior stroke/transient ischemic attack (TIA), as well as its impact on mortality, are not established. AIM To evaluate the impact of COVID-19 on in-hospital mortality, length of stay, and healthcare costs in patients with recurrent strokes. METHODS We identified admissions of recurrent stroke (current acute ischemic stroke admissions with at least one prior TIA or stroke) in patients with and without COVID-19 using ICD-10-CM codes using the National Inpatient Sample (2020). We analyzed the impact of COVID-19 on mortality following recurrent stroke admissions by subgroups. RESULTS Of 97455 admissions with recurrent stroke, 2140 (2.2%) belonged to the COVID-19-positive group. The COVID-19-positive group had a higher prevalence of diabetes and chronic kidney disease vs the COVID-19 negative group (P < 0.001). Among the subgroups, patients aged > 65 years, patients aged 45-64 years, Asians, Hispanics, whites, and blacks in the COVID-19 positive group had higher rates of all-cause mortality than the COVID-19 negative group (P < 0.01). Higher odds of in-hospital mortality were seen in the group aged 45-64 (OR: 8.40, 95%CI: 4.18-16.91) vs the group aged > 65 (OR: 7.04, 95%CI: 5.24-9.44), males (OR: 7.82, 95%CI: 5.38-11.35) compared to females (OR: 6.15, 95%CI: 4.12-9.18), and in Hispanics (OR: 15.47, 95%CI: 7.61-31.44) and Asians/Pacific Islanders (OR: 14.93, 95%CI: 7.22-30.87) compared to blacks (OR: 5.73, 95%CI: 3.08-10.68), and whites (OR: 5.54, 95%CI: 3.79-8.09). CONCLUSION The study highlights the increased risk of all-cause in-hospital mortality in recurrent stroke patients with COVID-19, with a more pronounced increase in middle-aged patients, males, Hispanics, or Asians.
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Affiliation(s)
- Rupak Desai
- Outcomes Research, Independent Researcher, Atlanta, GA 30033, United States
| | | | - Sai Anusha Akella
- Department of Internal Medicine, One Brooklyn Health- Interfaith Medical Center, Brooklyn, NY 11213, United States
| | - Adil Sarvar Mohammed
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI 48602, United States
| | - Mushfequa Hussain
- Department of Internal Medicine, Kamineni Institute of Medical Sciences, Narketpally 508254, India
| | - Abdul Aziz Mohammed
- Department of Internal Medicine, Kamineni Institute of Medical Sciences, Narketpally 508254, India
| | - Pakhal Saketha
- Department of Internal Medicine, Bhaskar Medical College, Moinabad 500075, Hyderabad, India
| | - Praveena Sunkara
- Department of Internal Medicine, MedStar Medical Group, Charlotte Hall, MD 20622, United States
| | - Jyotsna Gummadi
- Department of Medicine, Medstar Franklin Square Medical Center, Baltimore, MD 21237, United States
| | - Paritharsh Ghantasala
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI 48602, United States
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10
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Dorgalaleh A, Safdari SM, Tabibian S, Shams M, Dabbagh A, Rezazadeh A. Congenital Bleeding Disorders and COVID-19-A Systematic Literature Review. Semin Thromb Hemost 2024; 50:552-568. [PMID: 37758179 DOI: 10.1055/s-0043-1775733] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/03/2023]
Abstract
Hypercoagulability is a prominent feature of coronavirus disease 2019 (COVID-19) and can lead to fatal consequences. Although the impact of COVID-19 on several disorders is well-established, its effect on congenital bleeding disorders (CBDs) is not well-documented. To address this ambiguity, a systematic review was conducted on the available studies to determine the impact of COVID-19 and vaccination aimed to prevent COVID-19 on patients with CBDs. We performed a systematic literature review using relevant keywords and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. We conducted our search on the PubMed, Scopus, and Web of Science databases until July 2023. Out of 31 included studies, 12 case series covering 770 patients with CBD and COVID-19 were further analyzed. The majority of the patients had hemophilia A (n = 352, ∼46%) or hemophilia B (n = 74, ∼10%), while the remaining patients had von Willebrand disease (n = 43, 5.6%) or rare bleeding disorders (n = 27, 3.5%). A total of 25 deaths (3.2%) and 22 intensive care unit admissions (2.8%) were recorded. Bleeding complications were reported in the majority of the 12 case series (n = 7, 58.3%) and in most of the case reports (n = 8, ∼57%), while thrombotic complications were only reported in two studies (16.6%). The mortality rate ranged from 0% in five studies (41.6%) to 5.7% and the rate of hospitalization ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the thrombotic complication rate in one study was 6.9%. The mortality rate varied from 0 to 5.7%, and the hospitalization rate ranged from 0 to 40%. Bleeding complications were reported in a range of 0 to 81%, while the rate of thrombotic complications in one study was 6.9%. Vaccination was reported in five case series, which included 821 patients with CBDs with the majority having hemophilia A (n = 479; 67.2%) and hemophilia B (n = 85; ∼12%). The most frequently reported side effects were myalgia (6.5%), flu-like symptoms (4.8%), fever (4.7%), and headache (4%). COVID-19 in patients with CBDs appears to provoke thrombotic complications and bleeding events more frequently, as well as a higher rate of hospitalization, which may be partially due to the increased risk of bleeding events. Although it seems that patients with CBD have lower mortality rates, further studies are necessary to fully understand this, especially considering comorbidities and low number of available studies.
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Affiliation(s)
| | - Seyed Mehrab Safdari
- Departments of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shadi Tabibian
- Iranian Comprehensive Hemophilia Care Center, Blood and Viral Research Center, Tehran, Iran
| | - Mahmood Shams
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Ali Dabbagh
- Department of Anesthesia and Anesthesia Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azadeh Rezazadeh
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
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11
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Saconato M, Maselli-Schoueri JH, Malaque CMS, Marcusso RM, de Oliveira ACP, Batista LAN, Ultramari G, Lindoso JAL, Gonçalves MIR, Sztajnbok J. Postorotracheal intubation dysphagia in patients with COVID-19: A retrospective study. SAO PAULO MED J 2024; 142:e2022608. [PMID: 38808794 PMCID: PMC11126317 DOI: 10.1590/1516-3180.2022.0608.r3.14032024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 12/09/2023] [Accepted: 03/14/2024] [Indexed: 05/30/2024] Open
Abstract
BACKGROUND The cause of oropharyngeal dysphagia in patients with coronavirus disease (COVID-19) can be multifactorial and may underly limitations in swallowing rehabilitation. OBJECTIVE Analyze the factors related to dysphagia in patients with COVID-19 immediately after orotracheal extubation and the factors that influence swallowing rehabilitation. DESIGN AND SETTING A retrospective study. METHODS The presence of dysphagia was evaluated using the American Speech-Language Hearing Association National Outcome Measurement System (ASHA NOMS) scale and variables that influenced swallowing rehabilitation in 140 adult patients who required invasive mechanical ventilation for >48 h. RESULTS In total, 46.43% of the patients scored 1 or 2 on the ASHA NOMS (severe dysphagia) and 39.29% scored 4 (single consistency delivered orally) or 5 (exclusive oral diet with adaptations). Both the length of mechanical ventilation and the presence of neurological disorders were associated with lower ASHA NOMS scores (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.74-0.87 P < 0.05; and OR: 0.13, 95% CI: 0.61-0.29; P < 0.05, respectively). Age and the presence of tracheostomy were negatively associated with speech rehabilitation (OR: 0.92; 95% CI: 0.87--0.96; OR: 0.24; 95% CI: 0.80--0.75), and acute post-COVID-19 kidney injury requiring dialysis and lower scores on the ASHA NOMS were associated with longer time for speech therapy outcomes (β: 1.62, 95% CI, 0.70-3.17, P < 0.001; β: -1.24, 95% CI: -1.55--0.92; P < 0.001). CONCLUSION Prolonged orotracheal intubation and post-COVID-19 neurological alterations increase the probability of dysphagia immediately after extubation. Increased age and tracheostomy limited rehabilitation.
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Affiliation(s)
- Mariana Saconato
- PhD. Speech therapist, Technical manager of the Speech Therapy team, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
| | | | - Ceila Maria Sant’Ana Malaque
- PhD. Physician, Intensive Care Unit Physician, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
| | - Rosa Maria Marcusso
- MSc. Statistician, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
| | | | | | - Graziela Ultramari
- MSc. Physiotherapist, Head of the Diagnostic and Therapeutic Support Department, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
| | - José Angelo Lauletta Lindoso
- PhD. Physician, Director of the Diagnostic and Therapeutic Support Department, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
| | - Maria Inês Rebelo Gonçalves
- PhD. Speech therapist and Professor, Department of Speech Therapy, Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil
| | - Jaques Sztajnbok
- MD. Physician, Head of the Intensive Care Unit, Instituto de Infectologia Emílio Ribas (IIER), São Paulo (SP), Brazil
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12
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Mitsiakos G, Gialamprinou D, Kontovazainitis CG, Moraitis A, Katsaras G, Pouliakis A, Diamanti E. Coagulation assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infected pregnant women and their offspring by using rotational thromboelastometry (ROTEM). J Perinat Med 2024; 52:327-342. [PMID: 38353249 DOI: 10.1515/jpm-2023-0444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 01/11/2024] [Indexed: 03/07/2024]
Abstract
OBJECTIVES During pregnancy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection may intensify the gestational procoagulant state. Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) constitutes an exacerbated immunothrombosis response. There is limited data regarding the coagulation profile of SARS-CoV2-infected pregnant women, especially those with CAC, and the effect on their offspring. This prospective study aimed to compare the hemostatic profile of those women and their neonates with healthy mother-neonate pairs. METHODS Conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM) were employed to evaluate the hemostatic profiles. Neonates were assessed at birth and on the fourth day of life. RESULTS We enrolled 46 SARS-CoV2-infected pregnant women and 22 healthy controls who gave birth to 47 and 22 neonates, respectively. CAC was present in 10 participants. SARS-CoV2-infected pregnant women manifested slightly prolonged APTT and higher fibrinogen levels. Regarding ROTEM, we noted decreased FIBTEM CFT, with higher A10, A-angle, and MCF. The CAC group presented lower platelet count, increased fibrinogen levels, and higher FIBTEM A10 and MCF. PT was slightly prolonged at birth in neonates born to SARS-CoV2-infected mothers. During the fourth day of life, D-dimers were significantly increased. Concerning ROTEM, neonates born to SARS-CoV2-infected mothers showed lower FIBTEM CT at birth. CONCLUSIONS SARS-CoV2-infected pregnant women present a hypercoagulable profile. Hypercoagulability with elevated fibrinolysis and lower platelet count is observed in participants with CAC. The coagulation profile of neonates born to SARS-CoV2 mothers seems unaffected. Elevated D-dimers on the fourth day may reflect a neonatal inflammatory response to maternal SARS-CoV2.
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Affiliation(s)
- Georgios Mitsiakos
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
| | - Dimitra Gialamprinou
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
| | - Christos-Georgios Kontovazainitis
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
| | - Athanasios Moraitis
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
| | - Georgios Katsaras
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
| | - Abraham Pouliakis
- 2nd Department of Pathology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, PC, Greece
| | - Elissavet Diamanti
- 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, PC, Greece
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13
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Ramsay IA, Fountain H, Elarjani T, Govindarajan V, Silva M, Abdelsalam A, Burks JD, Starke RM, Luther E. Outcomes in patients with large vessel occlusion strokes undergoing mechanical thrombectomy with concurrent COVID-19: a nationwide retrospective analysis. J Neurointerv Surg 2024; 16:342-346. [PMID: 37263776 DOI: 10.1136/jnis-2023-020263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 05/15/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection. METHODS The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates. RESULTS Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis. CONCLUSIONS Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19.
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Affiliation(s)
- Ian A Ramsay
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Hayes Fountain
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Turki Elarjani
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Vaidya Govindarajan
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Michael Silva
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Ahmed Abdelsalam
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Joshua D Burks
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Robert M Starke
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Evan Luther
- Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
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14
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Boyarchuk O, Perestiuk V, Kosovska T, Volianska L. Coagulation profile in hospitalized children with COVID-19: pediatric age dependency and its impact on long COVID development. Front Immunol 2024; 15:1363410. [PMID: 38510249 PMCID: PMC10950941 DOI: 10.3389/fimmu.2024.1363410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 02/23/2024] [Indexed: 03/22/2024] Open
Abstract
Introduction Pulmonary endotheliopathy and microvascular immunothrombosis play a key role in acute COVID-19. Moreover, persistent endotheliopathy and heightened coagulability frequently occur in individuals recovering from COVID-19, suggesting the intriguing possibility of their role in the development of long COVID. The aim of our study was to investigate the coagulation profile in patients with COVID-19 based on age and their role in the development of long COVID. Methods We conducted a prospective single-center cohort study from September 2022 to August 2023. The study involved 190 patients younger than 18 years who were hospitalized at the Ternopil City Children's Hospital, Ukraine due to COVID-19. Patients underwent determination of coagulation profile in addition to the general clinical examination. After discharge from the hospital, patients were monitored for the presence of long COVID symptoms. Among the 157 participants who consented for follow-up, 62 patients (39.5%) had long COVID symptoms according to the WHO definition, while the rest (95 patients) did not have symptoms of long COVID (fully recovered). Results The study revealed the normal count of platelets in the majority of patients (86.8%), whereas abnormalities in the coagulation profile were revealed in 94.5% of children with COVID-19, and these changes were age-dependent. The patients were mostly presented with increased activated partial thromboplastin time (69.1%), prothrombin time (PT) (39.8%) and D-dimer (45.0%). There was no significant difference between the median of platelet levels and coagulation profile indicators between the groups with long COVID and recovered. Among children who developed persistent long COVID symptoms there was a statistically higher percentage of abnormal PT values (53% versus 36.1%, p=0.0432), with no significant differences in other coagulation profile indicators. Abnormal PT along with female gender, comorbidities, especially allergic pathology, nutritional disorder, including obesity, were determined as potential risk factors of the long COVID development (Odds ratio - 2.0611; 95% 1.0179-4.1737, p=0.0445). Conclusions The study highlights the need for more extensive research into the coagulation profiles of pediatric populations, considering age-specific factors. This could enhance our understanding of thromboinflammation in COVID-19 and its potential contribution to the development of persistent symptoms.
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15
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Hulshof AM, Nab L, van Rosmalen F, de Kok J, Mulder MMG, Hellenbrand D, Sels JWEM, Ten Cate H, Cannegieter SC, Henskens YMC, van Bussel BCT. Rotational thromboelastometry as a biomarker for mortality - The Maastricht Intensive Care COVID cohort. Thromb Res 2024; 234:51-58. [PMID: 38159324 DOI: 10.1016/j.thromres.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/18/2023] [Accepted: 12/18/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Patients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. METHODS Patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. RESULTS Of the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8-24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. CONCLUSIONS ROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.
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Affiliation(s)
- Anne-Marije Hulshof
- Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
| | - Linda Nab
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Frank van Rosmalen
- Department of Intensive Care, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Jip de Kok
- Department of Intensive Care, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Mark M G Mulder
- Department of Intensive Care, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Anesthesiology, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Dave Hellenbrand
- Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Jan Willem E M Sels
- Department of Intensive Care, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Hugo Ten Cate
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands; Thrombosis Expert Centre Maastricht, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Suzanne C Cannegieter
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Medicine - Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands
| | - Yvonne M C Henskens
- Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
| | - Bas C T van Bussel
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Intensive Care, Maastricht University Medical Centre+, Maastricht, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands
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16
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Chakabva MS, Polina S, Brauner M, McGuire M, Brown Z, Akthar T, Todt M, Polina A, Nova FF. Comparison of Standard Versus Intermediate Prophylaxis Dose for Venous Thromboembolism Prophylaxis in Patients Hospitalized With COVID-19 Infection. Hosp Pharm 2024; 59:94-101. [PMID: 38223865 PMCID: PMC10786052 DOI: 10.1177/00185787231194997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
Background: COVID-19 infection is associated with a high risk of venous thromboembolism (VTE) events. VTE prophylaxis reduces the risk of these events. The optimal dose of VTE prophylaxis however remains uncertain. Objectives: To compare the incidence of VTE in patients treated with either standard dose VTE versus intermediate dose VTE prophylaxis. Methods: In this retrospective cohort study, we analyzed data from 1786 adult patients admitted into the hospital with polymerase chain reaction confirmed COVID-19 infection between April 2020 to September 2021. For analysis, patients were divided into 2 cohorts: either standard dose prophylaxis treatment group (patients who received either unfractionated heparin 5000units 3 times a day or enoxaparin 30-40 mg daily subcutaneously) or intermediate dose VTE prophylaxis group (patients received either unfractionated heparin 7500 units 3 times daily or enoxaparin 30-40 mg twice a day subcutaneously). The primary outcome was incidence of VTE events described as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Secondary outcome was bleeding events. Results: During the study period, 398 (22%) patients were primarily treated with standard dose VTE prophylaxis, whereas 1388 (78%) patients were treated with intermediate dose VTE prophylaxis. There was a significantly higher incidence of venous thromboembolism events noted in the standard dose prophylaxis treatment group when compared with the intermediate dose prophylaxis group (25/398 (6.3%) vs 35/1388 (2.5%) P < .001, [Odds Ratio 2.6197, 95% confidence interval = 1.5482-4.4327]). Multivariable-adjusted logistic regression, adjusting for age, obesity, and smoking, with the intermediate dose prophylaxis treatment group as the referent category revealed higher odds for incident venous thromboembolism events in the standard dose prophylaxis group. There was no statistically significant difference in bleeding events between the 2 treatment groups (9 (2.3%) for standard dose prophylaxis group vs 46 (3.3%) for intermediate dose prophylaxis group P = .26). Conclusions: Among patients hospitalized with COVID-19 infection, patients receiving intermediate dose VTE prophylaxis experienced lower incident rates of venous thromboembolism events compared to those receiving standard dose VTE prophylaxis without a statistically significant increase in the risk of bleeding events.
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Affiliation(s)
| | | | | | | | | | | | | | - Aws Polina
- Wayne State/Detroit Medical Center Internal Medicine Residency, Detroit, MI, USA
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17
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Poor H, Yaeger K, Deeba S, Edwards S, Chapman E, Liu X, Eisenberg E, Tolbert TM, Shpiner A, Mocco J. Tenecteplase With Concomitant Anticoagulation for Acute Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial. Cureus 2024; 16:e54298. [PMID: 38496180 PMCID: PMC10944634 DOI: 10.7759/cureus.54298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2024] [Indexed: 03/19/2024] Open
Abstract
Background Pulmonary thrombosis and thromboembolism play a significant role in the physiologic derangements seen in COVID-19 acute respiratory failure. The effect of thrombolysis with tenecteplase on patient outcomes is unknown. Methods We conducted a randomized, controlled, double-blind, phase II trial comparing tenecteplase versus placebo in patients with COVID-19 acute respiratory failure (NCT04505592). Patients with COVID-19 acute respiratory failure were randomized to tenecteplase 0.25 mg/kg or placebo in a 2:1 proportion. Both groups received therapeutic heparin for at least 72 hours. Results Thirteen patients were included in the trial. Eight patients were randomized to tenecteplase and five were randomized to placebo. At 28 days, 63% (n = 5) of patients assigned to the treatment group were alive and free from respiratory failure compared to 40% (n = 2) in the placebo arm (p = 0.43). Mortality at 28 days was 25% (n = 2) in the treatment arm and 20% (n = 1) in the control arm (p = 1.0). No patients in the treatment arm developed renal failure by 28 days compared to 60% (n = 3) in the placebo arm (p = 0.07). Major bleeding occurred in 25% (n = 2) of the treatment arm and 20% (n = 1) in the placebo arm; however, no patients in either arm experienced intracranial hemorrhage. Conclusions Tenecteplase with concomitant heparin may improve patient outcomes in patients with COVID-19 respiratory failure. As this study was limited by a small sample size, larger confirmatory studies are needed.
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Affiliation(s)
- Hooman Poor
- Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Kurt Yaeger
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Serina Deeba
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Sydney Edwards
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Emily Chapman
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Xinyan Liu
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Elliot Eisenberg
- Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Thomas M Tolbert
- Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Aaron Shpiner
- Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - J Mocco
- Neurological Surgery, Icahn School of Medicine at Mount Sinai, New York, USA
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18
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Imzil A, Mansoury O, Oulahbib A, Adarmouch L, Serhane H. Comparative study of the severity of Covid-19 infection between female and male patients. Niger Med J 2024; 65:56-66. [PMID: 39006174 PMCID: PMC11238169 DOI: 10.60787/nmj-v65i1-451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/16/2024] Open
Abstract
Background Different studies have identified the prognostic factors of COVID-19 infection. These studies have revealed that COVID-19 infection is more severe in males than in females. The aim of our study was to compare the severity of COVID-19 infection between males and females in terms of clinical, biological, radiological, and evolutionary aspects. Methodology This is a cross-sectional observational study conducted in patients hospitalized with COVID-19 infection over a 6-month period from 1 August 2021 to 1 February 2022. Results The comparison of clinical, biological, radiological, and evolutionary severity factors of covid-19 infection between the two sexes revealed that this infection was more severe in males. Statistically significant differences were noted for the rate of high dimers (p =0.01) and for lung involvement greater than 25% on chest CT (Computed tomography) (p =0.008). Conclusion The severity of covid-19 infection in men is due to biological differences between men and women in the renin-angiotensin system, the immune system, genetics, and sex hormones. Further research into the pathophysiological mechanisms behind this finding is needed.
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Affiliation(s)
- Aboubekr Imzil
- Pneumology Department, Faculty of Medicine and Pharmacy of Agadir, Souss-Massa University Hospital, Ibn Zohr University, Agadir, Morocco
| | - Ouassim Mansoury
- Clinical Research Department, Mohammed VI University Hospital, Marrakesh, Morocco
- Community Medicine and Public Health Department, Bioscience and Health Research Laboratory, School of Medicine, Cadi Ayyad University, Marrakesh, Morocco
| | - Abdelmajid Oulahbib
- Pneumology Department, Faculty of Medicine and Pharmacy of Agadir, Souss-Massa University Hospital, Ibn Zohr University, Agadir, Morocco
| | - Latifa Adarmouch
- Clinical Research Department, Mohammed VI University Hospital, Marrakesh, Morocco
- Community Medicine and Public Health Department, Bioscience and Health Research Laboratory, School of Medicine, Cadi Ayyad University, Marrakesh, Morocco
| | - Hind Serhane
- Pneumology Department, Faculty of Medicine and Pharmacy of Agadir, Souss-Massa University Hospital, Ibn Zohr University, Agadir, Morocco
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19
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Khaleq MAA. Effect of Enoxaparin on D-dimer levels in hospitalized Corona Virus patients with a comparison of its level in patients with comorbid conditions. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2024; 77:828-833. [PMID: 38865643 DOI: 10.36740/wlek202404131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2024]
Abstract
OBJECTIVE Aim: The main goal is to assess the levels of comorbid diseases and examine the changes in D-dimer in hospitalized patients before and following SC enoxaparin medication. PATIENTS AND METHODS Material and Methods: At the Al-Yarmouk Teaching Hospital in Baghdad, Iraq, from October 2022 to May 2023, 86 patients who were hospitalized and had severe to critical COVID-19 infections provided data for a retrospective analysis. RESULTS Results: The medical records of all COVID-19 patients who were hospitalized and whose D-dimer level was greater than 0.5 mg/l and who were given enoxaparin (40 mg subcutaneously) were reviewed with the requisite authorization from the relevant authorities. The D-dimer level was assessed following therapy on the day of admission and day five after commencing enoxaparin. An examination of 86 case records revealed that persons with COVID-19 had significantly decreased D-dimer levels after taking subcutaneous enoxaparin (p-value<0.0001). The comorbidities (diabetes mellitus, hypertension) of patients who received the drug were compared. CONCLUSION Conclusions: Enoxaparin and other anticoagulants were utilized to treat the coagulopathy brought on by COVID-19. Low molecular weight heparin enoxaparin has demonstrated positive outcomes in the management of VTE. A decrease in D-dimer level is anticipated when COVID-19 patients are treated with subcutaneous enoxaparin, partly because decreased coagulation results in lower fibrin formation.
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Zheng YR, Weng B, Zhang QL, Wang SB, Chen Q. Successful use of VA-ECMO in the treatment of an infant with SARS-CoV-2 associated ARDS: A case experience of China and literature review. Respir Med Case Rep 2023; 46:101948. [PMID: 38046460 PMCID: PMC10689932 DOI: 10.1016/j.rmcr.2023.101948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 11/02/2023] [Accepted: 11/08/2023] [Indexed: 12/05/2023] Open
Affiliation(s)
- Yi-Rong Zheng
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Bin Weng
- Department of Pediatric Intensive Care Unit, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Qi-Liang Zhang
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Shi-Biao Wang
- Department of Pediatric Intensive Care Unit, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Qiang Chen
- Department of Cardiac Surgery, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
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21
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Awoke MA, Adane A, Assefa B, Getawa S, Legese GL, Yimer M. Hematological parameters and their predictive value for assessing disease severity in laboratory-confirmed COVID-19 patients: a retrospective study. AMERICAN JOURNAL OF BLOOD RESEARCH 2023; 13:117-129. [PMID: 37736538 PMCID: PMC10509465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/07/2023] [Indexed: 09/23/2023]
Abstract
BACKGROUND The coronavirus disease 19 (COVID-19) infection has spread globally and caused a substantial amount of mortality and morbidity. Early detection of severe infections will improve care and reduce deaths. The use of hematological parameters in predicting COVID-19 disease severity, patient outcomes, and early risk stratification is limited. Therefore, the study was aimed at determining hematological parameters and their predictive value for assessing disease severity in laboratory-confirmed COVID-19 patients in Northwest Ethiopia. METHODS A retrospective cross-sectional study was conducted at the University of Gondar comprehensive specialized hospital and Tibebe Ghion comprehensive specialized referral hospital on 253 patients diagnosed with COVID-19 and admitted between March 2021 and February 2022. Data were extracted, and entered into Epi-data 4.2.0.0, and analyzed using SPSS version 25 software. Hematological parameters were provided as the median and interquartile range (IQR). Categorical variables were represented by their frequency, and the χ2 test was applied to compare observed results with expected results. The receiver-operating curve (ROC) was used to establish the predictive value of hematological parameters for COVID-19 severity. A p-value < 0.05 was considered statistically significant. RESULTS On a total of 253 patients, there were 43.87% severe cases, with a mortality rate of 26.9%. The ROC analysis showed the optimal cutoff values for hematological parameters were ANC (3370), lymphocyte (680), NLR (9.34), PLR (290.77), platelets (332,000), and WBCs (4390.65). The area under the curve (AUC) values for NLR (0.679) and ANC (0.631) were high, with the highest sensitivity and specificity, and could potentially be used to predict COVID-19 severity. CONCLUSION This study proved that high NLR and high ANC have prognostic value for assessing disease severity in COVID-19. Thus, assessing and considering these hematological parameters when triaging COVID-19 patients may prevent complications and improve the patient's outcome.
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Affiliation(s)
- Mezgebu Alemayehu Awoke
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
| | - Ayinshet Adane
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
| | - Belete Assefa
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
| | - Solomon Getawa
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
| | - Gebrehiwot Lema Legese
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
| | - Mekonen Yimer
- Department of Internal Medicine, School of Medicine, College of Medicine and Health Sciences, University of GondarGondar, Ethiopia
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22
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Abed Alwan M, Jasim Mohammed Shallal M. Detection of biochemical markers levels among COVID-19 patients,
recovered and vaccinated groups of people. BIONATURA 2023; 8:1-8. [DOI: 10.21931/rb/css/2023.08.01.77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The new virus first appeared in the Chinese city of Wuhan in 2019 and
spread around the world, like the outbreak of the Coronavirus (COVID-19), causing severe acute respiratory syndrome in humans, which can be fatal to individuals at risk. The primary purposes of this study are to assess the diagnostic power
of the following biochemical (D dimer, CRP, LDH and serum ferritin) markers in
identifying the diagnosis and severity of COVID-19 and to find out the differences in these hematological and biochemical markers among COVID 19 patients
and recovered. The study included (50) patients diagnosed with COVID-19 (25
males and 25 females) who visited Al-Hussein Teaching Hospital in ThiQar
province, (50) Patients recovering from COVID-19 infection, (50) People who
have received COVID-19 vaccines and (50: 25 people were vaccinated with Sinopharm and 25 people were vaccinated with Pfizer) healthy subjects as a control
group. The study population age ranged from (20-70 years) old. Specialist physicians diagnosed all patients with COVID-19 in this study, which was confirmed
by clinical and laboratory tests, especially polymerase chain reaction PCR. The
results of the current study have shown that there is a significant difference(PValue < 0.05) between the study groups according to the age group in each of the
levels (D dimer, LDH, serum ferritin). The current study also revealed a significant difference between the study groups according to gender in each of (D. dimer, LDH), and there is no significant difference in each of (CRP, serum ferritin). A significant difference is expected where the difference between the two
averages is between the patients' COVID-19 group and the control group, the recovered group, or the vaccinated group(LSD of D. dimer >95.10, LSD of
CRP>11.86, S. ferritin >120.61, LSD of LDH>75.45) and no significant between
control and recovered. An increase in the levels of the following vital signs for
patients with COVID-19: D dimer, CRP, LDH, and serum ferritin. In the recovered groups, the levels were normal.
Keywords: biochemical markers, COVID19, recovered and vaccinated group of
people
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23
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Abha Mishra KM, Podili R, Pathlavath TS, Sethi KK. A critical review on brain and heart axis response in COVID-19 patients: Molecular mechanisms, mediators, biomarkers, and therapeutics. J Biochem Mol Toxicol 2023; 37:e23409. [PMID: 37341157 DOI: 10.1002/jbt.23409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 06/01/2023] [Accepted: 06/08/2023] [Indexed: 06/22/2023]
Abstract
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.
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Affiliation(s)
- K M Abha Mishra
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Runesh Podili
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Teja S Pathlavath
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
| | - Kalyan K Sethi
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research Guwahati, Assam, India
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24
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Ermerak NO, Yildizeli SO, Kocakaya D, Mutlu B, Ak K, Tas S, Yildizeli B. Surgical Treatment of Another Sequalae of COVID-19: Post-COVID CTEPH. Thorac Cardiovasc Surg 2023; 71:413-417. [PMID: 36944361 DOI: 10.1055/a-2059-4513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is still an ongoing entity and every day we face new sequalae of the disease. We hereby present surgical results of patients who are treated for post-COVID chronic thromboembolic pulmonary hypertension. METHODS Data were collected among patients who underwent pulmonary endarterectomy and had a diagnosis of post-COVID chronic thromboembolic pulmonary hypertension. All data were retrospectively reviewed from a prospectively conducted database. Operative mortality was described as death in hospital or within 30 days of surgery. RESULTS Eleven patients (seven males, four females; median age, 52 [22-63] years) were identified. Pulmonary vascular resistance improved significantly from 572 dyn/s/cm-5 (240-1,192) to 240 (195-377) dyn/s/cm-5 (p < 0.005). Significant difference was also detected in median mPAP, as it decreased from 40 mm Hg (24-54) to 24 mm Hg (15-36) following surgery (p < 0.005). Mortality was observed in one patient due to sepsis on the fifth postoperative day. Median time from COVID-19 disease to surgery was 12 months (6-24). Median length of hospital stay of the survivors was 10 days (8-14). CONCLUSION In the new era of chronic thromboembolic pulmonary hypertension, hybrid approach including surgery, balloon pulmonary angioplasty, and medical treatment has been recommended. pulmonary endarterectomy is still the only curative treatment when the disease is surgically accessible. We hereby report the first publication of post-COVID chronic thromboembolic pulmonary hypertension patients who were surgically treated. As we see a lot of long-term symptoms and clinical manifestations in patients who had COVID-19, we should always remember chronic thromboembolic pulmonary hypertension in the differential diagnosis.
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Affiliation(s)
- Nezih Onur Ermerak
- Department of Thoracic Surgery, Marmara University School of Medicine, Istanbul, Turkey
| | | | - Derya Kocakaya
- Department of Pulmonology, Marmara University School of Medicine, Istanbul, Turkey
| | - Bulent Mutlu
- Department of Cardiology, Marmara University School of Medicine, Istanbul, Turkey
| | - Koray Ak
- Department of Cardiovascular Surgery, Marmara University School of Medicine, Istanbul, Turkey
| | - Serpil Tas
- Department of Cardiovascular Surgery, Kartal Kosuyolu Training and Research Hospital, Istanbul, Turkey
| | - Bedrettin Yildizeli
- Department of Thoracic Surgery, Marmara University School of Medicine, Istanbul, Turkey
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25
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Rodrigues A, Dias Domingues T, Nobre Jesus G, Garção A, Rodrigues AR, Jacinto Correia C, Leal Pereira C, Correia D, Beleza Á, Ribeiro JM. COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study. ACTA MEDICA PORT 2023; 36:496-505. [PMID: 37429589 DOI: 10.20344/amp.19475] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/31/2023] [Indexed: 07/12/2023]
Abstract
INTRODUCTION COVID-19-associated coagulopathy includes systemic and endothelial inflammation with coagulation dysregulation related to immunothrombosis. The aim of this study was to characterize this complication of SARS-CoV-2 infection in patients with moderate to severe COVID-19. METHODS An open-label, prospective observational study conducted in patients with COVID-19 moderate to severe acute respiratory failure admitted to an intensive care unit (ICU). Coagulation testing, including thromboelastometry, biochemical analysis and clinical variables, were collected at prespecified time points during the 30 days of ICU stay. RESULTS The study included 145 patients, 73.8% male, with a median age of 68 years (interquartile range - IQR 55 - 74). The most prevalent comorbidities were arterial hypertension (63.4%), obesity (44.1%) and diabetes (22.1%). Simplified acute physiology score II (SAPS II) was on average 43.5 (11 - 105) and sequential organ failure assessment (SOFA) at admission was 7.5 (0 - 14). During ICU stay, 66.9% of patients underwent invasive mechanical ventilation and 18.4% extracorporeal membrane oxygenation support; thrombotic and hemorrhagic events occurred in 22.1% and 15.1% of the patients respectively; anticoagulation with heparin was present in 99.2% of patients since early ICU stay. Death occurred in 35% of patients. Longitudinal studies revealed changes in almost all coagulation tests during the ICU stay. SOFA score, lymphocyte counts, some biochemical, inflammatory and coagulation parameters, including hypercoagulability and hypofibrinolysis seen in thromboelastometry, differed significantly (p < 0.05), between ICU admission and discharge. Hypercoagulability and hypofibrinolysis persisted throughout ICU hospitalization, showing higher incidence and severity in non-survivors. CONCLUSION COVID-19-associated coagulopathy is characterized by hypercoagulability and hypofibrinolysis from ICU admission, and persisted throughout the clinical course in severe COVID-19. These changes were more pronounced in patients with higher disease burden and in non-survivors.
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Affiliation(s)
- Anabela Rodrigues
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Tiago Dias Domingues
- Centro de Estatística e Aplicações - CEAUL. Faculdade de Ciências. Universidade de Lisboa. Lisbon. Portugal
| | - Gustavo Nobre Jesus
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon; Clínica Universitária de Medicina Intensiva. Faculdade de Medicina. Universidade de Lisboa. Lisbon. Portugal
| | - Ana Garção
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Ana Rita Rodrigues
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Catarina Jacinto Correia
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Carla Leal Pereira
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Dulce Correia
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - Álvaro Beleza
- Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
| | - João Miguel Ribeiro
- Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. Portugal
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Lo Re V, Dutcher SK, Connolly JG, Perez-Vilar S, Carbonari DM, DeFor TA, Djibo DA, Harrington LB, Hou L, Hennessy S, Hubbard RA, Kempner ME, Kuntz JL, McMahill-Walraven CN, Mosley J, Pawloski PA, Petrone AB, Pishko AM, Rogers Driscoll M, Steiner CA, Zhou Y, Cocoros NM. Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study. BMJ MEDICINE 2023; 2:e000421. [PMID: 37303490 PMCID: PMC10254785 DOI: 10.1136/bmjmed-2022-000421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 05/03/2023] [Indexed: 06/13/2023]
Abstract
Objective To measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before and during covid-19 vaccine availability and compare results to patients with ambulatory diagnosed influenza. Design Retrospective cohort study. Setting Four integrated health systems and two national health insurers in the US Food and Drug Administration's Sentinel System. Participants Patients with ambulatory diagnosed covid-19 when vaccines were unavailable in the US (period 1, 1 April-30 November 2020; n=272 065) and when vaccines were available in the US (period 2, 1 December 2020-31 May 2021; n=342 103), and patients with ambulatory diagnosed influenza (1 October 2018-30 April 2019; n=118 618). Main outcome measures Arterial thromboembolism (hospital diagnosis of acute myocardial infarction or ischemic stroke) and venous thromboembolism (hospital diagnosis of acute deep venous thrombosis or pulmonary embolism) within 90 days after ambulatory covid-19 or influenza diagnosis. We developed propensity scores to account for differences between the cohorts and used weighted Cox regression to estimate adjusted hazard ratios of outcomes with 95% confidence intervals for covid-19 during periods 1 and 2 versus influenza. Results 90 day absolute risk of arterial thromboembolism with covid-19 was 1.01% (95% confidence interval 0.97% to 1.05%) during period 1, 1.06% (1.03% to 1.10%) during period 2, and with influenza was 0.45% (0.41% to 0.49%). The risk of arterial thromboembolism was higher for patients with covid-19 during period 1 (adjusted hazard ratio 1.53 (95% confidence interval 1.38 to 1.69)) and period 2 (1.69 (1.53 to 1.86)) than for patients with influenza. 90 day absolute risk of venous thromboembolism with covid-19 was 0.73% (0.70% to 0.77%) during period 1, 0.88% (0.84 to 0.91%) during period 2, and with influenza was 0.18% (0.16% to 0.21%). Risk of venous thromboembolism was higher with covid-19 during period 1 (adjusted hazard ratio 2.86 (2.46 to 3.32)) and period 2 (3.56 (3.08 to 4.12)) than with influenza. Conclusions Patients diagnosed with covid-19 in the ambulatory setting had a higher 90 day risk of admission to hospital with arterial thromboembolism and venous thromboembolism both before and after covid-19 vaccine availability compared with patients with influenza.
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Affiliation(s)
- Vincent Lo Re
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sarah K Dutcher
- Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - John G Connolly
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | - Silvia Perez-Vilar
- Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
| | - Dena M Carbonari
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Djeneba Audrey Djibo
- CVS Health Clinical Trial Services, an affiliate of Aetna, CVS Health Company, Blue Bell, PA, USA
| | - Laura B Harrington
- Kaiser Permanente Washington Health Research Institute and Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Laura Hou
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | - Sean Hennessy
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Rebecca A Hubbard
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Maria E Kempner
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | - Jennifer L Kuntz
- Kaiser Permanente Northwest Center for Health Research, Portland, OR, USA
| | | | - Jolene Mosley
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | | | - Andrew B Petrone
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | - Allyson M Pishko
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Meighan Rogers Driscoll
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
| | - Claudia A Steiner
- Kaiser Permanente Colorado Institute for Health Research, Aurora, CO, USA
| | - Yunping Zhou
- Humana Healthcare Research, Inc, Louisville, KY, USA
| | - Noelle M Cocoros
- Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- Department of Population Medicine, Harvard Pilgrim Health Care Inc, Wellesley, MA, USA
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27
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Gomes JC, de Freitas Barbosa VA, de Santana MA, de Lima CL, Calado RB, Júnior CRB, de Almeida Albuquerque JE, de Souza RG, de Araújo RJE, Moreno GMM, Soares LAL, Júnior LARM, de Souza RE, dos Santos WP. Rapid protocols to support COVID-19 clinical diagnosis based on hematological parameters. RESEARCH ON BIOMEDICAL ENGINEERING 2023; 39:509-539. [PMCID: PMC10239225 DOI: 10.1007/s42600-023-00286-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/22/2023] [Indexed: 08/27/2024]
Abstract
Purpose In December 2019, the Covid-19 pandemic began in the world. To reduce mortality, in addiction to mass vaccination, it is necessary to massify and accelerate clinical diagnosis, as well as creating new ways of monitoring patients that can help in the construction of specific treatments for the disease. Objective In this work, we propose rapid protocols for clinical diagnosis of COVID-19 through the automatic analysis of hematological parameters using evolutionary computing and machine learning. These hematological parameters are obtained from blood tests common in clinical practice. Method We investigated the best classifier architectures. Then, we applied the particle swarm optimization algorithm (PSO) to select the most relevant attributes: serum glucose, troponin, partial thromboplastin time, ferritin, D-dimer, lactic dehydrogenase, and indirect bilirubin. Then, we assessed again the best classifier architectures, but now using the reduced set of features. Finally, we used decision trees to build four rapid protocols for Covid-19 clinical diagnosis by assessing the impact of each selected feature. The proposed system was used to support clinical diagnosis and assessment of disease severity in patients admitted to intensive and semi-intensive care units as a case study in the city of Paudalho, Brazil. Results We developed a web system for Covid-19 diagnosis support. Using a 100-tree random forest, we obtained results for accuracy, sensitivity, and specificity superior to 99%. After feature selection, results were similar. The four empirical clinical protocols returned accuracies, sensitivities and specificities superior to 98%. Conclusion By using a reduced set of hematological parameters common in clinical practice, it was possible to achieve results of accuracy, sensitivity, and specificity comparable to those obtained with RT-PCR. It was also possible to automatically generate clinical decision protocols, allowing relatively accurate clinical diagnosis even without the aid of the web decision support system.
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Affiliation(s)
| | - Valter Augusto de Freitas Barbosa
- Academic Unit of Serra Talhada, Rural Federal University of Pernambuco, Serra Talhada, Brazil
- Federal University of Pernambuco, Recife, Brazil
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Kammerer T, Walzl A, Müller T, Groene P, Roveri G, Turner R, Roche J, Gatterer H, Siebenmann C, Schäfer ST. Effects of Hypobaric Hypoxia on Coagulation in Healthy Subjects Exposed to 3,500 m Altitude. High Alt Med Biol 2023; 24:94-103. [PMID: 37339401 DOI: 10.1089/ham.2022.0154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/22/2023] Open
Abstract
Kammerer, Tobias, Anna Walzl, Thomas Müller, Philipp Groene, Giulia Roveri, Rachel Turner, Johanna Roche, Hannes Gatterer, Christoph Siebenmann, and Simon T. Schäfer. Effects of hypobaric hypoxia on coagulation in healthy subjects exposed to 3,500 m altitude. High Alt Med Biol. 24:94-103, 2023. Background: Hypoxia is discussed as a trigger for prothrombotic changes both in intensive care and high altitude medicine. This research study aimed to evaluate the effect of isolated hypobaric hypoxia (HH) on coagulation in females in a highly standardized setting. Methods: Twelve healthy female subjects were studied under HH (equivalent to 3,500 m) and normoxia (NX) during two 4-day sojourns, in a strictly controlled crossover design. Nutrition, fluid intake, hormonal status (i.e., menstrual cycle variation), and physical stress were standardized. Functional coagulation and blood lysis were measured by viscoelastometry and compared between HH and NX. In addition, plasma-based coagulation tests (PBCTs), namely prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII coagulation activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and von Willebrand factor ristocetin cofactor activity (vWF:RCo) were measured. Results: Neither for Viscoelastic Haemostatic Assays nor for PBCTs significant changes were found for HH compared with NX (all p > 0.05). Specifically, the lysis ability, as well as clotting time, clot formation, clot amplitude, and maximum clot firmness unchanged were similar between HH and NX. This also applied to all other variables. Conclusion: We demonstrate that moderate HH per se has no influence on blood coagulation in healthy females.
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Affiliation(s)
- Tobias Kammerer
- Department of Anaesthesiology and Intensive Care Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Department of Anaesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Anna Walzl
- Department of Anaesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Thomas Müller
- Department of Laboratory Medicine, Hospital Voecklabruck, Voecklabruck, Austria
| | - Philipp Groene
- Department of Anaesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Giulia Roveri
- Eurac Research, Institute of Mountain Emergency Medicine, Bolzano, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Rachel Turner
- Eurac Research, Institute of Mountain Emergency Medicine, Bolzano, Italy
| | - Johanna Roche
- Eurac Research, Institute of Mountain Emergency Medicine, Bolzano, Italy
| | - Hannes Gatterer
- Eurac Research, Institute of Mountain Emergency Medicine, Bolzano, Italy
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL-Private University for Health Sciences and Health Technology, Hall in Tirol, Austria
| | | | - Simon T Schäfer
- Department of Anaesthesiology, Ludwig-Maximilians-University Munich, Munich, Germany
- Department of Anesthesia, Intensive Care Medicine, Emergency Medicine and Pain Therapy, University Hospital, Carl-von-Ossietzky University Oldenburg, Klinikum Oldenburg AöR, Oldenburg, Germany
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Yamga E, Mullie L, Durand M, Cadrin-Chenevert A, Tang A, Montagnon E, Chartrand-Lefebvre C, Chassé M. Interpretable clinical phenotypes among patients hospitalized with COVID-19 using cluster analysis. Front Digit Health 2023; 5:1142822. [PMID: 37114183 PMCID: PMC10128042 DOI: 10.3389/fdgth.2023.1142822] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 03/13/2023] [Indexed: 04/29/2023] Open
Abstract
Background Multiple clinical phenotypes have been proposed for coronavirus disease (COVID-19), but few have used multimodal data. Using clinical and imaging data, we aimed to identify distinct clinical phenotypes in patients admitted with COVID-19 and to assess their clinical outcomes. Our secondary objective was to demonstrate the clinical applicability of this method by developing an interpretable model for phenotype assignment. Methods We analyzed data from 547 patients hospitalized with COVID-19 at a Canadian academic hospital. We processed the data by applying a factor analysis of mixed data (FAMD) and compared four clustering algorithms: k-means, partitioning around medoids (PAM), and divisive and agglomerative hierarchical clustering. We used imaging data and 34 clinical variables collected within the first 24 h of admission to train our algorithm. We conducted a survival analysis to compare the clinical outcomes across phenotypes. With the data split into training and validation sets (75/25 ratio), we developed a decision-tree-based model to facilitate the interpretation and assignment of the observed phenotypes. Results Agglomerative hierarchical clustering was the most robust algorithm. We identified three clinical phenotypes: 79 patients (14%) in Cluster 1, 275 patients (50%) in Cluster 2, and 203 (37%) in Cluster 3. Cluster 2 and Cluster 3 were both characterized by a low-risk respiratory and inflammatory profile but differed in terms of demographics. Compared with Cluster 3, Cluster 2 comprised older patients with more comorbidities. Cluster 1 represented the group with the most severe clinical presentation, as inferred by the highest rate of hypoxemia and the highest radiological burden. Intensive care unit (ICU) admission and mechanical ventilation risks were the highest in Cluster 1. Using only two to four decision rules, the classification and regression tree (CART) phenotype assignment model achieved an AUC of 84% (81.5-86.5%, 95 CI) on the validation set. Conclusions We conducted a multidimensional phenotypic analysis of adult inpatients with COVID-19 and identified three distinct phenotypes associated with different clinical outcomes. We also demonstrated the clinical usability of this approach, as phenotypes can be accurately assigned using a simple decision tree. Further research is still needed to properly incorporate these phenotypes in the management of patients with COVID-19.
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Affiliation(s)
- Eric Yamga
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
| | - Louis Mullie
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
| | - Madeleine Durand
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
| | | | - An Tang
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Department of Radiology and Nuclear Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
| | - Emmanuel Montagnon
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
| | - Carl Chartrand-Lefebvre
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
- Department of Radiology and Nuclear Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
| | - Michaël Chassé
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
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Nunez Lopez YO, Iliuk A, Casu A, Parikh A, Smith JS, Corbin K, Lupu D, Pratley RE. Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus. Diabetes Res Clin Pract 2023; 197:110565. [PMID: 36736734 PMCID: PMC9890887 DOI: 10.1016/j.diabres.2023.110565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 01/22/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023]
Abstract
Recent studies suggest that extracellular vesicles (EVs) play a role in the pathogenesis of SARS-CoV-2 infection and the severity of COVID-19. However, their role in the interaction between COVID-19 and type 2 diabetes (T2D) has not been addressed. Here, we characterized the circulating EV proteomic and phosphoproteomic landscape in patients with and without T2D hospitalized with COVID-19 or non-COVID-19 acute respiratory illness (RSP). We detected differentially expressed protein and phosphoprotein signatures that effectively characterized the study groups. The trio of immunomodulatory and coagulation proteins C1QA, C1QB, and C1QC appeared to be a central cluster in both the COVID-19 and T2D functional networks. PKCβ appeared to be retained in cells by being diverted from EV pathways and contribute to the COVID-19 and T2D interaction via a PKC/BTK/TEC axis. EV-shuttled CASP3 and ROCK1 appeared to be coregulated and likely contribute to disease interactions in patients with COVID-19 and T2D. Predicted activation of AMPK, MAPK, and SYK appeared to also play important roles driving disease interaction. These results suggest that activated cellular kinases (i.e., PKC, AMPK, MAPK, and SYK) and multiple EV-shuttled kinases (i.e., PKCβ, BTK, TEC, MAP2K2, and ROCK1) may play key roles in severe COVID-19, particularly in patients with comorbid diabetes.
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Affiliation(s)
- Yury O Nunez Lopez
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Anton Iliuk
- Department of Biochemistry, Purdue University, West Lafayette, IN 47907, United States; Tymora Analytical Operations, West Lafayette, IN 47906, United States.
| | - Anna Casu
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Amay Parikh
- Division of Critical Care, AdventHealth Medical Group, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Joshua S Smith
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Karen Corbin
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Daniel Lupu
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States
| | - Richard E Pratley
- Translational Research Institute, AdventHealth Orlando, Orlando, FL 32804, United States.
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Coupland LA, Rabbolini DJ, Schoenecker JG, Crispin PJ, Miller JJ, Ghent T, Medcalf RL, Aneman AE. Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study. Crit Care 2023; 27:55. [PMID: 36765421 PMCID: PMC9912243 DOI: 10.1186/s13054-023-04329-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/22/2023] [Indexed: 02/12/2023] Open
Abstract
BACKGROUND Fibrinolysisis is essential for vascular blood flow maintenance and is triggered by endothelial and platelet release of tissue plasminogen activator (t-PA). In certain critical conditions, e.g. sepsis, acute respiratory failure (ARF) and trauma, the fibrinolytic response is reduced and may lead to widespread thrombosis and multi-organ failure. The mechanisms underpinning fibrinolysis resistance include reduced t-PA expression and/or release, reduced t-PA and/or plasmin effect due to elevated inhibitor levels, increased consumption and/or clearance. This study in critically ill patients with fibrinolysis resistance aimed to evaluate the ability of t-PA and plasminogen supplementation to restore fibrinolysis with assessment using point-of-care ClotPro viscoelastic testing (VET). METHODS In prospective, observational studies, whole-blood ClotPro VET evaluation was carried out in 105 critically ill patients. In 32 of 58 patients identified as fibrinolysis-resistant (clot lysis time > 300 s on the TPA-test: tissue factor activated coagulation with t-PA accelerated fibrinolysis), consecutive experimental whole-blood VET was carried out with repeat TPA-tests spiked with additional t-PA and/or plasminogen and the effect on lysis time determined. In an interventional study in a patient with ARF and fibrinolysis resistance, the impact of a 24 h intravenous low-dose alteplase infusion on coagulation and fibrinolysis was prospectively monitored using standard ClotPro VET. RESULTS Distinct response groups emerged in the ex vivo experimental VET, with increased fibrinolysis observed following supplementation with (i) t-PA only or (ii) plasminogen and t-PA. A baseline TPA-test lysis time of > 1000 s was associated with the latter group. In the interventional study, a gradual reduction (25%) in serial TPA-test lysis times was observed during the 24 h low-dose alteplase infusion. CONCLUSIONS ClotPro viscoelastic testing, the associated TPA-test and the novel experimental assays may be utilised to (i) investigate the potential mechanisms of fibrinolysis resistance, (ii) guide corrective treatment and (iii) monitor in real-time the treatment effect. Such a precision medicine and personalised treatment approach to the management of fibrinolysis resistance has the potential to increase treatment benefit, while minimising adverse events in critically ill patients. TRIAL REGISTRATION VETtiPAT-ARF, a clinical trial evaluating ClotPro-guided t-PA (alteplase) administration in fibrinolysis-resistant patients with ARF, is ongoing (ClinicalTrials.gov NCT05540834 ; retrospectively registered September 15th 2022).
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Affiliation(s)
- Lucy A. Coupland
- grid.415994.40000 0004 0527 9653Intensive Care Unit, Liverpool Hospital, Liverpool, Australia ,grid.429098.eIngham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170 Australia
| | - David J. Rabbolini
- grid.1013.30000 0004 1936 834XKolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney, Sydney, Australia ,grid.410556.30000 0001 0440 1440Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Jonathan G. Schoenecker
- grid.412807.80000 0004 1936 9916Department of Orthopaedics and Pharmacology, Vanderbilt University Medical Center, Nashville, TN USA
| | - Philip J. Crispin
- grid.413314.00000 0000 9984 5644Haematology Department, The Canberra Hospital, Canberra, Australia ,grid.1001.00000 0001 2180 7477The Australian National University Medical School, Canberra, Australia
| | - Jennene J. Miller
- grid.415994.40000 0004 0527 9653Intensive Care Unit, Liverpool Hospital, Liverpool, Australia
| | - Tony Ghent
- grid.413154.60000 0004 0625 9072Intensive Care Unit, Gold Coast University Hospital, South Port, Australia
| | - Robert L. Medcalf
- grid.1002.30000 0004 1936 7857Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
| | - Anders E. Aneman
- grid.415994.40000 0004 0527 9653Intensive Care Unit, Liverpool Hospital, Liverpool, Australia ,grid.429098.eIngham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170 Australia
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Zhu G, Modepalli S, Anand M, Li H. Computational modeling of hypercoagulability in COVID-19. Comput Methods Biomech Biomed Engin 2023; 26:338-349. [PMID: 36154346 DOI: 10.1080/10255842.2022.2124858] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 100 million people worldwide and claimed millions of lives. While the leading cause of mortality in COVID-19 patients is the hypoxic respiratory failure from acute respiratory distress syndrome, there is accumulating evidence that shows excessive coagulation also increases the fatalities in COVID-19. Thus, there is a pressing demand to understand the association between COVID-19-induced hypercoagulability and the extent of formation of undesired blood clots. Mathematical modeling of coagulation has been used as an important tool to identify novel reaction mechanisms and to identify targets for new drugs. Here, we employ the coagulation factor data of COVID-19 patients reported from published studies as inputs for two mathematical models of coagulation to identify how the concentrations of coagulation factors change in these patients. Our simulation results show that while the levels of many of the abnormal coagulation factors measured in COVID-19 patients promote the generation of thrombin and fibrin, two key components of blood clots, the increased level of fibrinogen and then the reduced level of antithrombin are the factors most responsible for boosting the level of fibrin and thrombin, respectively. Altogether, our study demonstrates the potential of mathematical modeling to identify coagulation factors responsible for the increased clot formation in COVID-19 patients where clinical data is scarce.
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Affiliation(s)
- Ge Zhu
- Center for Biomedical Engineering, Brown University, Providence, USA
| | | | - Mohan Anand
- Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Hyderabad, India
| | - He Li
- School of Chemical, Materials & Biomedical Engineering, University of Georgia, Athens, USA
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Sanjay S, Bhakti Mistra S, Patro SK, Kawali A, Shetty R, Mahendradas P. Systemic Markers in Ophthalmic Manifestations of Post Corona Virus Disease-19 (COVID-19). Ocul Immunol Inflamm 2023; 31:410-415. [PMID: 35138993 DOI: 10.1080/09273948.2021.2025253] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Corona virus disease (COVID-19) has been associated with ophthalmic manifestations which can occur during or following the infection. PURPOSE To explore the systemic status in ophthalmic patients who had a recent history of COVID-19 or those with positive COVID-19 antibody status. METHODS Retrospective case series. RESULTS 30 patients with history of COVID-19 infection and positive COVID-19 antibodies were included in the study. The median age was 49 years (mean 48.7 ± 13.7 years), 20 were males (66.7%) and 10 (33.3%) were females. Patients with VA>/= 6/60 were included in group 1 and those with VA<6/60 were included in group 2. D-dimer/serum Ferritin levels were raised in group 2 compared to group 1with (p=0.013)/(p=0.018) respectively. CONCLUSION Serum D-dimer and ferritin levels were statistically significant and were higher in patients with sight threatening ocular manifestations. ESR and CRP were raised even after recovery from COVID-19 although they were not statistically significant.
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Affiliation(s)
- Srinivasan Sanjay
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Sai Bhakti Mistra
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Sithun Kumar Patro
- Department of Community Medicine, MKCG Medical College, Brahmapur, India
| | - Ankush Kawali
- Department of Uveitis and Ocular Immunology, Narayana Nethralaya, Bangalore, India
| | - Rohit Shetty
- Department of Neuro-ophthalmology, Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India
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Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
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Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
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Rashid K, Waheed MA, Khan Y, Afridi A, Ansar F, Elzouki A. Pneumomediastinum in association with Covid-19: A less commonly considered differential diagnosis for worsening respiratory failure. Qatar Med J 2023; 2023:4. [PMID: 36606063 PMCID: PMC9811311 DOI: 10.5339/qmj.2023.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 11/08/2022] [Indexed: 01/05/2023] Open
Abstract
We have reported here two cases of coronavirus disease-2019 (COVID-19) patients aged 29 and 68 years who were diagnosed with pneumomediastinum (PM). PM is a rare complication that is being reported in association with COVID-19. Patients with COVID-19 can present with a variety of etiologies that make them vulnerable to PM. Respiratory complications due to COVID-19 are widely known, and it presents as mild to severe and critical illness. Spontaneous PM is a known complication of COVID-19. Despite seeming to be a lesser-known condition, PM can have a significant impact on disease progression and prognosis. We have presented here two contrasting cases of PM. The first patient was young and with moderate COVID-19 pneumonia and PM, while the second one was an old man with severe COVID-19 pneumonia manifestations. Both patients were diagnosed with PM, but their outcomes were completely different.
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Affiliation(s)
| | - Muhammad Aamir Waheed
- Hamad Medical Corporation, Qatar. E-mail: ORCID: E-mail: 0000-0002-9056-5245,E-mail: ORCID: E-mail: 0000-0002-9056-5245
| | | | - Adnan Afridi
- Northampton General Hospital NHS Trust, Acute Medicine
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Krumpolec P, Kodada D, Nyáriová N, Repiská V, Minárik G. COVID-19 and Diabetes Mellitus: Mutual Interplay of Two Diseases. Curr Diabetes Rev 2023; 19:e130922208761. [PMID: 36100987 DOI: 10.2174/1573399819666220913113146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/16/2022] [Accepted: 08/09/2022] [Indexed: 11/22/2022]
Abstract
Currently, when the world is fighting against the rapidly spreading pandemic of COVID-19, the silent epidemic of diabetes should not be set aside. In comparison, while COVID- 19 led to about 6 million deaths in 2021, diabetes caused 6.7 million deaths in the same year. Diabetes mellitus is a serious risk factor for worse outcomes in COVID-19 patients. Moreover, it seems that there is a bidirectional relationship between pre-existing diabetes pandemic and the rapidly spreading COVID-19 pandemic. In this article, we summarize mechanisms by which SARS-CoV-2 infects the host cell and discuss the bidirectional relationship between diabetes and COVID-19. We also focus on clinical variables in which diabetic patients differ from non-diabetic patients and which could have promising predictive value for the course and outcome of diabetic COVID-19 patients' therapy management.
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Affiliation(s)
| | - Dominik Kodada
- Medirex Group Academy n.p.o., Novozamocka 67, Nitra, Slovakia
- Faculty of Medicine, Department of Clinical Biology, Genetics and Clinical Genetics, Comenius University in Bratislava, Sasinkova 4, Bratislava, Slovakia
| | - Nikola Nyáriová
- Medirex Group Academy n.p.o., Novozamocka 67, Nitra, Slovakia
- Faculty of Medicine, Department of Clinical Biology, Genetics and Clinical Genetics, Comenius University in Bratislava, Sasinkova 4, Bratislava, Slovakia
| | - Vanda Repiská
- Faculty of Medicine, Department of Clinical Biology, Genetics and Clinical Genetics, Comenius University in Bratislava, Sasinkova 4, Bratislava, Slovakia
| | - Gabriel Minárik
- Medirex Group Academy n.p.o., Novozamocka 67, Nitra, Slovakia
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Hobohm L, Sagoschen I, Barco S, Farmakis IT, Fedeli U, Koelmel S, Gori T, Espinola-Klein C, Münzel T, Konstantinides S, Keller K. COVID-19 infection and its impact on case fatality in patients with pulmonary embolism. Eur Respir J 2023; 61:13993003.00619-2022. [PMID: 35981745 PMCID: PMC9411730 DOI: 10.1183/13993003.00619-2022] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 07/20/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Although a high prevalence of pulmonary embolism (PE) has been reported in association with coronavirus disease 2019 (COVID-19) in critically ill patients, nationwide data on the outcome of hospitalised patients with COVID-19 and PE are still limited. Thus, we investigated seasonal trends and predictors of in-hospital death in patients with COVID-19 and PE in Germany. METHODS We used a German nationwide inpatient sample to analyse data on hospitalisations among COVID-19 patients with and without PE during 2020, and to detect changes in PE prevalence and case fatality in comparison with 2019. RESULTS We analysed 176 137 COVID-19 hospitalisations in 2020; PE was recorded in 1.9% (n=3362) of discharge certificates. Almost one-third of patients with COVID-19 and PE died during the in-hospital course (28.7%) compared with COVID-19 patients without PE (17.7%). Between 2019 and 2020, numbers of PE-related hospitalisations were largely unchanged (98 485 versus 97 718), whereas the case fatality rate of PE increased slightly in 2020 (from 12.7% to 13.1%; p<0.001). Differences in case fatality were found between PE patients with and without COVID-19 in 2020 (28.7% versus 12.5%; p<0.001), corresponding to a 3.1-fold increased risk of PE-related death (OR 3.16, 95% CI 2.91-3.42; p<0.001) in the presence of COVID-19. CONCLUSIONS In Germany, the prevalence of PE events during hospitalisations was similar in 2019 and 2020. However, the fatality rate among patients with both COVID-19 and PE was substantially higher than that in those with only one of these diseases, suggesting a life-threatening additive prognostic impact of the COVID-19-PE combination.
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Affiliation(s)
- Lukas Hobohm
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- L. Hobohm and I. Sagoschen contributed equally and share first authorship
| | - Ingo Sagoschen
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- L. Hobohm and I. Sagoschen contributed equally and share first authorship
| | - Stefano Barco
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Angiology, University Hospital Zurich, Zurich, Switzerland
| | - Ioannis T Farmakis
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ugo Fedeli
- Epidemiological Department, Azienda Zero, Padova, Italy
| | - Sebastian Koelmel
- Department of Internal Medicine, Triemli Hospital Zurich, Zurich, Switzerland
| | - Tommaso Gori
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Christine Espinola-Klein
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Thomas Münzel
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany
| | - Stavros Konstantinides
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Karsten Keller
- Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
- Medical Clinic VII, Department of Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany
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Elmoursy MM, Bakr MS, Mohamed ES, Ragaee MA. The Incidence of Sudden Sensorineural Hearing Loss (SSNHL) in COVID-19 Patients in Tertiary Care Referral Units. SN COMPREHENSIVE CLINICAL MEDICINE 2023; 5:87. [PMID: 36845674 PMCID: PMC9942031 DOI: 10.1007/s42399-023-01420-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/31/2023] [Indexed: 02/23/2023]
Abstract
COVID-19 is a new pandemic infectious disease that emerged in Wuhan, China, at the end of 2019. We aimed to evaluate the sudden sensorineural hearing loss (SSNHL) prevalence after COVID-19 infection or even vaccination. This is a two-center retrospective, observational cross-sectional study performed at tertiary care referral Audiovestibular Medicine Units at the period between August 1, 2020, and October 31, 2021. All SSNHL patients diagnosed in a period of a month with COVID-19 or vaccinated with a COVID-19 vaccine were included in this study. Fifty-three cases with confirmed COVID-19 and one patient vaccinated with a COVID-19 vaccine 1 week before, who reported sudden sensory neural hearing loss, were included in this study. Forty-eight patients had unilateral hearing loss and 6 patients had bilateral hearing loss. Forty-nine patients had typical COVID-19 symptoms; one patient discovered them after complaining of anosmia and ageusia and one patient after COVID-19 vaccination; and three patients were complaining only from hearing loss and had a PCR test for nasopharyngeal swabs to prove infection. Different degrees of SSNHL ranged from mild to severe and most of the patients had severe hearing loss. With more patients, COVID-19 may be a potential factor in sudden sensorineural hearing loss. It should be kept in mind that SSNHL may be the only indicator used to identify COVID-19 cases.
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Affiliation(s)
| | - Mohamed Salama Bakr
- Audiovestibular Medicine Unit, ENT Department, Assiut University, Asyut, Egypt
| | - Enass Sayed Mohamed
- Audiovestibular Medicine Unit, ENT Department, Assiut University, Asyut, Egypt
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Respiratory psychophysiology and COVID-19: A research agenda. Biol Psychol 2023; 176:108473. [PMID: 36535514 PMCID: PMC9756651 DOI: 10.1016/j.biopsycho.2022.108473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 12/03/2022] [Accepted: 12/04/2022] [Indexed: 12/23/2022]
Abstract
After multiple waves of the COVID-19 pandemic, it has become clear that the impact of SARS-CoV-2 will carry on for years to come. Acutely infected patients show a broad range of disease severity, depending on virus variant, vaccination status, age and the presence of underlying medical and physical conditions, including obesity. Additionally, a large number of patients who have been infected with the virus present with post-COVID syndrome. In September 2020, the International Society for the Advancement of Respiratory Psychophysiology organized a virtual interest meeting on 'Respiratory research in the age of COVID-19', which aimed to discuss how research in respiratory psychophysiology could contribute to a better understanding of psychophysiological interactions in COVID-19. In the resulting current paper, we propose an interdisciplinary research agenda discussing selected research questions on acute and long-term neurobiological, physiological and psychological outcomes and mechanisms related to respiration and the airways in COVID-19, as well as research questions on comorbidity and potential treatment options, such as physical rehabilitation.
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Salem RO, Nuzhat A, Zaheer S, Kallash MA. Laboratory Characteristics on SARS-CoV-2 Infection among Patients with Diabetes Mellitus: A Single-Center Retrospective Study. J Diabetes Res 2023; 2023:9940250. [PMID: 36712996 PMCID: PMC9876690 DOI: 10.1155/2023/9940250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 12/13/2022] [Accepted: 01/06/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Diabetic patients have been severely affected by COVID-19 infection. It has been reported that the disease is more progressive leading to venous and arterial thromboembolism, due to multiple factors. This study was conducted to determine the hematologic parameters including D-dimer in diabetic patients with COVID-19 infection in association with disease severity and treatment. METHOD This retrospective cohort study was conducted at King Fahad Medical City, Saudi Arabia, after obtaining IRB approval, by collecting data regarding all laboratory parameters, disease severity, and anticoagulant treatment of COVID-19 diabetic patients (n = 159) from medical records from March to December 2020. RESULT Mean value of white blood cells, neutrophils, monocytes, eosinophils, lymphocyte monocyte ratio, C-reactive protein, serum ferritin, and LDH levels was elevated in severe cases than in mild cases with statistical significant increase in HbA1c (0.047), serum fibrinogen (0.007), C-reactive protein (0.005), serum ferritin (0.034), and serum LDH (0.015). Mortality was observed in 14 (8.8%) patients mostly with severe COVID-19 with diabetes. In our study, treatment with low molecular weight heparin was not significantly related to severity. A logistic regression analysis indicated an association of some laboratory parameters with severity and mortality of the disease. CONCLUSION The routine blood parameters if detected early will enable physicians to identify severe cases of COVID-19 patients with Diabetes for prompt treatment and save considerable time and resources.
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Affiliation(s)
- Raneem O. Salem
- Basic Medical Sciences Department, King Fahad Medical City, King Saud Bin Abdul-Aziz University of Health Sciences, Riyadh, Saudi Arabia
| | - Ayesha Nuzhat
- Basic Medical Sciences Department, King Fahad Medical City, King Saud Bin Abdul-Aziz University of Health Sciences, Riyadh, Saudi Arabia
| | - Shawana Zaheer
- Diabetic Center and Endocrinology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Majd Aldeen Kallash
- Diabetic Center and Endocrinology, King Fahad Medical City, Riyadh, Saudi Arabia
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RETRACTED ARTICLE: Serum level estimation of some biomarkers in diabetic and non-diabetic COVID-19 infected patients. APPLIED NANOSCIENCE 2023; 13:3133. [PMID: 35136705 PMCID: PMC8812352 DOI: 10.1007/s13204-021-02167-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 10/09/2021] [Indexed: 12/22/2022]
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Chen-Goodspeed A, Dronavalli G, Zhang X, Podbielski JM, Patel B, Modis K, Cotton BA, Wade CE, Cardenas JC. Antithrombin Activity is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness. Acta Haematol 2022; 146:117-124. [PMID: 36538905 PMCID: PMC9940263 DOI: 10.1159/000528584] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients. METHODS A single-center, prospective observational study enrolling SARS-CoV-2 positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-FXa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using Chi-square tests. Multivariable logistic regression was used to determine the association between AT activity and mortality. RESULTS In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP). CONCLUSIONS Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies.
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Affiliation(s)
- Amber Chen-Goodspeed
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Goutham Dronavalli
- Department of Internal Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Xu Zhang
- Center for Clinical and Translational Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Jeanette M. Podbielski
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Bela Patel
- Department of Internal Medicine, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Katalin Modis
- Department of Surgery, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA
| | - Bryan A. Cotton
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA,Red Duke Trauma Institute, Memorial Hermann - Texas Medical Center, Houston, Texas, USA
| | - Charles E. Wade
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA,Red Duke Trauma Institute, Memorial Hermann - Texas Medical Center, Houston, Texas, USA
| | - Jessica C. Cardenas
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas, USA,*Jessica C Cardenas,
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Bruhn-Olszewska B, Davies H, Sarkisyan D, Juhas U, Rychlicka-Buniowska E, Wójcik M, Horbacz M, Jąkalski M, Olszewski P, Westholm JO, Smialowska A, Wierzba K, Torinsson Naluai Å, Jern N, Andersson LM, Järhult JD, Filipowicz N, Tiensuu Janson E, Rubertsson S, Lipcsey M, Gisslén M, Hultström M, Frithiof R, Dumanski JP. Loss of Y in leukocytes as a risk factor for critical COVID-19 in men. Genome Med 2022; 14:139. [PMID: 36514076 PMCID: PMC9747543 DOI: 10.1186/s13073-022-01144-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 11/23/2022] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription. METHODS Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs. RESULTS Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11). CONCLUSIONS We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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Affiliation(s)
- Bożena Bruhn-Olszewska
- grid.8993.b0000 0004 1936 9457Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Hanna Davies
- grid.8993.b0000 0004 1936 9457Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Daniil Sarkisyan
- grid.8993.b0000 0004 1936 9457Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Ulana Juhas
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Edyta Rychlicka-Buniowska
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Magdalena Wójcik
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Monika Horbacz
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Marcin Jąkalski
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Paweł Olszewski
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Jakub O. Westholm
- grid.10548.380000 0004 1936 9377National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Stockholm, Sweden
| | - Agata Smialowska
- grid.10548.380000 0004 1936 9377National Bioinformatics Infrastructure Sweden, Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Stockholm, Sweden
| | - Karol Wierzba
- grid.11451.300000 0001 0531 3426Department and Clinic of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland
| | - Åsa Torinsson Naluai
- grid.8761.80000 0000 9919 9582Department of Laboratory Medicine, Institute of Biomedicine and Biobank Core Facility, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Niklas Jern
- grid.8761.80000 0000 9919 9582Department of Laboratory Medicine, Institute of Biomedicine and Biobank Core Facility, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Lars-Magnus Andersson
- grid.8761.80000 0000 9919 9582Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ,grid.1649.a000000009445082XDepartment of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Josef D. Järhult
- grid.8993.b0000 0004 1936 9457Zoonosis Science Center, Department of Medical Sciences, Uppsala, Sweden, Uppsala University, Uppsala, Sweden
| | - Natalia Filipowicz
- grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Eva Tiensuu Janson
- grid.8993.b0000 0004 1936 9457Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University, Uppsala, Sweden
| | - Sten Rubertsson
- grid.8993.b0000 0004 1936 9457Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden
| | - Miklós Lipcsey
- grid.8993.b0000 0004 1936 9457Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden ,grid.8993.b0000 0004 1936 9457Hedenstierna laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Magnus Gisslén
- grid.8761.80000 0000 9919 9582Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ,grid.1649.a000000009445082XDepartment of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Michael Hultström
- grid.8993.b0000 0004 1936 9457Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden ,grid.8993.b0000 0004 1936 9457Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Robert Frithiof
- grid.8993.b0000 0004 1936 9457Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden
| | - Jan P. Dumanski
- grid.8993.b0000 0004 1936 9457Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden ,grid.11451.300000 0001 0531 34263P-Medicine Laboratory, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
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Matsuoka A, Koami H, Shinada K, Sakamoto Y. Investigation of differences in coagulation characteristics between hospitalized patients with SARS-CoV-2 Alpha, Delta, and Omicron variant infection using rotational thromboelastometry (ROTEM): A single-center, retrospective, observational study. J Clin Lab Anal 2022; 36:e24796. [PMID: 36441617 PMCID: PMC9756981 DOI: 10.1002/jcla.24796] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 11/12/2022] [Accepted: 11/19/2022] [Indexed: 01/10/2024] Open
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 Omicron variant has a low rate of serious illness, is highly contagious, and has spread rapidly since January 2022. The number of severe cases and deaths remains problematic. Here, we aimed to elucidate the coagulation pathology of Omicron-infected patients using rotational thromboelastometry. METHODS Patients with coronavirus disease 2019, hospitalized and treated from January 2021 to April 2022, were included. The Alpha-Delta and Omicron groups were defined during admission. Blood tests, clinical course, and rotational thromboelastometry measurements were compared using a propensity score-matched cohort. RESULTS Both groups had 21 patients each. Lactate dehydrogenase (Alpha-Delta group [interquartile range] vs. Omicron group [interquartile range]; 449 [368-518] U/L vs. 241 [196-398] U/L, p = 0.01) and ferritin (1428 [1145-3061] ng/dl vs. 481 [188-881] ng/dl, p = 0.0002) levels were significantly lower in the Omicron group. In rotational thromboelastometry, the thrombus hardness indexes FIBTEM A5 (29 [23-34] mm vs. 23 [18-28] mm, p = 0.034) and maximum clot firmness (34 [27-40] mm vs. 26 [21-33] mm, p = 0.021) were significantly lower in the Omicron group, whereas the fibrinolysis index FIBTEM LI60 (98 [92-100] % vs. 100 [100-100] %, p = 0.0082) was higher. CONCLUSION Severe coagulation abnormalities may be less likely in Omicron-infected patients than in those infected with the previous Alpha and Delta variants.
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Affiliation(s)
- Ayaka Matsuoka
- Department of Emergency and Critical Care Medicine Faculty of MedicineSaga UniversitySaga CityJapan
| | - Hiroyuki Koami
- Department of Emergency and Critical Care Medicine Faculty of MedicineSaga UniversitySaga CityJapan
| | - Kota Shinada
- Department of Emergency and Critical Care Medicine Faculty of MedicineSaga UniversitySaga CityJapan
| | - Yuichiro Sakamoto
- Department of Emergency and Critical Care Medicine Faculty of MedicineSaga UniversitySaga CityJapan
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Hypercoagulability in critically ill patients with COVID 19, an observational prospective study. PLoS One 2022; 17:e0277544. [PMID: 36417476 PMCID: PMC9683576 DOI: 10.1371/journal.pone.0277544] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 10/30/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. DESIGN Prospective observational study. SETTING Monocentric, intensive care, University Hospital of Clermont Ferrand, France. PATIENTS Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. INTERVENTIONS Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 μg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. MEASUREMENTS AND MAIN RESULTS Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. CONCLUSIONS Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.
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Martinelli N, Rigoni AM, De Marchi S, Osti N, Donini M, Montagnana M, Castagna A, Pattini P, Udali S, De Franceschi L, Tinazzi E, Mazzi F, Moruzzi S, Argentino G, Delfino L, Sartori G, Azzini AM, Tacconelli E, Van Dreden P, Lippi G, Girelli D, Olivieri O, Friso S, Pizzolo F. High Plasma Levels of Activated Factor VII-Antithrombin Complex Point to Increased Tissue Factor Expression in Patients with SARS-CoV-2 Pneumonia: A Potential Link with COVID-19 Prothrombotic Diathesis. Diagnostics (Basel) 2022; 12:diagnostics12112792. [PMID: 36428852 PMCID: PMC9689539 DOI: 10.3390/diagnostics12112792] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/04/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.
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Affiliation(s)
- Nicola Martinelli
- Department of Medicine, University of Verona, 37129 Verona, Italy
- Correspondence: ; Tel.: +39-045-8126658; Fax: +39-045-8027473
| | - Anna Maria Rigoni
- Angiology Unit, Department of Cardiovascular and Thoracic, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy
| | - Sergio De Marchi
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Nicola Osti
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Martino Donini
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Martina Montagnana
- Section of Clinical Biochemistry, University of Verona, 37129 Verona, Italy
| | | | - Patrizia Pattini
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Silvia Udali
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | | | - Elisa Tinazzi
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Filippo Mazzi
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Sara Moruzzi
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | | | - Lorenzo Delfino
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Giulia Sartori
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | - Anna Maria Azzini
- Department of Diagnostics and Public Health, University of Verona, 37129 Verona, Italy
| | - Evelina Tacconelli
- Department of Diagnostics and Public Health, University of Verona, 37129 Verona, Italy
| | - Patrick Van Dreden
- Clinical Research Department, Diagnostica Stago, 92230 Gennevilliers, France
| | - Giuseppe Lippi
- Section of Clinical Biochemistry, University of Verona, 37129 Verona, Italy
| | - Domenico Girelli
- Department of Medicine, University of Verona, 37129 Verona, Italy
| | | | - Simonetta Friso
- Department of Medicine, University of Verona, 37129 Verona, Italy
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Turnic TN, Popadic V, Klasnja S, Sekulic A, Nikolic N, Zivkovic V, Jeremic N, Andjic M, Draginic N, Srejovic I, Jeremic J, Zdravkovic M, Jakovljevic V. Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7920915. [PMID: 36338343 PMCID: PMC9633192 DOI: 10.1155/2022/7920915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/13/2022] [Accepted: 10/07/2022] [Indexed: 11/24/2022]
Abstract
Introduction There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. Aim The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. Results The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). Conclusion The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.
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Affiliation(s)
- Tamara Nikolic Turnic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia
- N.A.Semashko Public Health and Healthcare Department, F.F. Erismann Institute of Public Health, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Viseslav Popadic
- University Clinical Hospital Center Bežanijska kosa, Belgrade, Serbia
| | - Slobodan Klasnja
- University Clinical Hospital Center Bežanijska kosa, Belgrade, Serbia
| | - Ana Sekulic
- University Clinical Hospital Center Bežanijska kosa, Belgrade, Serbia
| | - Novica Nikolic
- University Clinical Hospital Center Bežanijska kosa, Belgrade, Serbia
| | - Vladimir Zivkovic
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Department of Pharmacology, 1st Moscow State Medical, University IM Sechenov, Trubetskaya street 8, str. 2, 119991 Moscow, Russia
| | - Nevena Jeremic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia
- I.M. Shechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, Russia
| | - Marijana Andjic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Nevena Draginic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Ivan Srejovic
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Department of Pharmacology, 1st Moscow State Medical, University IM Sechenov, Trubetskaya street 8, str. 2, 119991 Moscow, Russia
| | - Jovana Jeremic
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Serbia
| | - Marija Zdravkovic
- University Clinical Hospital Center Bežanijska kosa, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Jakovljevic
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia
- Department of Human Pathology, 1st Moscow State Medical, University IM Sechenov, Trubetskaya street 8, str. 2, 119991 Moscow, Russia
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Urwyler P, Moser S, Trendelenburg M, Sendi P, Osthoff M. Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression. Mol Immunol 2022; 150:99-113. [PMID: 36030710 PMCID: PMC9393183 DOI: 10.1016/j.molimm.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/07/2022] [Accepted: 08/15/2022] [Indexed: 11/30/2022]
Abstract
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is associated with a clinical spectrum ranging from asymptomatic carriers to critically ill patients with complications including thromboembolic events, myocardial injury, multisystemic inflammatory syndromes and death. Since the beginning of the pandemic several therapeutic options emerged, with a multitude of randomized trials, changing the medical landscape of COVID-19. The effect of various monoclonal antibodies, antiviral, anti-inflammatory and anticoagulation drugs have been studied, and to some extent, implemented into clinical practice. In addition, a multitude of trials improved the understanding of the disease and emerging evidence points towards a significant role of the complement system, kallikrein-kinin, and contact activation system as drivers of disease in severe COVID-19. Despite their involvement in COVID-19, treatments targeting these plasmatic cascades have neither been systematically studied nor introduced into clinical practice, and randomized studies with regards to these treatments are scarce. Given the multiple-action, multiple-target nature of C1 inhibitor (C1-INH), the natural inhibitor of these cascades, this drug may be an interesting candidate to prevent disease progression and combat thromboinflammation in COVID-19. This narrative review will discuss the current evidence with regards to the involvement of these plasmatic cascades as well as endothelial cells in COVID-19. Furthermore, we summarize the evidence of C1-INH in COVID-19 and potential benefits and pitfalls of C1-INH treatment in COVID-19.
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Affiliation(s)
- Pascal Urwyler
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Stephan Moser
- Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Marten Trendelenburg
- Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Parham Sendi
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Michael Osthoff
- Department of Clinical Research and Department of Biomedicine, University of Basel, Basel, Switzerland; Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
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Arbănași EM, Halmaciu I, Kaller R, Mureșan AV, Arbănași EM, Suciu BA, Coșarcă CM, Cojocaru II, Melinte RM, Russu E. Systemic Inflammatory Biomarkers and Chest CT Findings as Predictors of Acute Limb Ischemia Risk, Intensive Care Unit Admission, and Mortality in COVID-19 Patients. Diagnostics (Basel) 2022; 12:2379. [PMID: 36292068 PMCID: PMC9600434 DOI: 10.3390/diagnostics12102379] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/10/2022] [Accepted: 09/27/2022] [Indexed: 01/08/2023] Open
Abstract
Background: Numerous tools, including inflammatory biomarkers and lung injury severity scores, have been evaluated as predictors of thromboembolic events and the requirement for intensive therapy in COVID-19 patients. This study aims to verify the predictive role of inflammatory biomarkers [monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), Systemic Inflammation Response Index (SIRI), and Aggregate Index of Systemic Inflammation (AISI)] and the CT Severity Score in acute limb ischemia (ALI) risk, intensive unit care (ICU) admission, and mortality in COVID-19 patients.; Methods: The present study was designed as an observational, analytical, retrospective cohort study and included all patients older than 18 years of age with a diagnosis of COVID-19 infection, confirmed through real time-polymerase chain reaction (RT-PCR), and admitted to the County Emergency Clinical Hospital of Targu-Mureș, Romania, and Modular Intensive Care Unit of UMFST “George Emil Palade” of Targu Mures, Romania between January 2020 and December 2021. Results: Non-Survivors and “ALI” patients were associated with higher incidence of cardiovascular disease [atrial fibrillation (AF) p = 0.0006 and p = 0.0001; peripheral arterial disease (PAD) p = 0.006 and p < 0.0001], and higher pulmonary parenchyma involvement (p < 0.0001). Multivariate analysis showed a high baseline value for MLR, NLR, PLR, SII, SIRI, AISI, and the CT Severity Score independent predictor of adverse outcomes for all recruited patients (all p < 0.0001). Moreover, the presence of AF and PAD was an independent predictor of ALI risk and mortality. Conclusions: According to our findings, higher MLR, NLR, PLR, SII, SIRI, AISI, and CT Severity Score values at admission strongly predict ALI risk, ICU admission, and mortality. Moreover, patients with AF and PAD had highly predicted ALI risk and mortality but no ICU admission.
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Affiliation(s)
- Emil Marian Arbănași
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
| | - Ioana Halmaciu
- Department of Anatomy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
- Department of Radiology, Mures County Emergency Hospital, 540136 Targu Mures, Romania
| | - Réka Kaller
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
| | - Adrian Vasile Mureșan
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
- Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
| | - Eliza Mihaela Arbănași
- Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
| | - Bogdan Andrei Suciu
- Department of Anatomy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
- First Clinic of Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
| | - Cătălin Mircea Coșarcă
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
- Department of Anatomy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
| | - Ioana Iulia Cojocaru
- First Clinic of Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
| | - Razvan Marian Melinte
- Department of Orthopedics, Regina Maria Health Network, 540098 Targu Mures, Romania
- Department of Orthopedics, Humanitas MedLife Hospital, 400664 Cluj Napoca, Romania
| | - Eliza Russu
- Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania
- Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
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50
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Bösch J, Rugg C, Schäfer V, Lichtenberger P, Staier N, Treichl B, Rajsic S, Peer A, Schobersberger W, Fries D, Bachler M. Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients. Semin Thromb Hemost 2022; 48:850-857. [PMID: 36174602 DOI: 10.1055/s-0042-1756304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008-0-012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH-anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.
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Affiliation(s)
- Johannes Bösch
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Christopher Rugg
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Volker Schäfer
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Philipp Lichtenberger
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Nikolai Staier
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Benjamin Treichl
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Sasa Rajsic
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Andreas Peer
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Wolfgang Schobersberger
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT - Private University for Health Sciences and Health Technology, Hall i.T., Austria
| | - Dietmar Fries
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
| | - Mirjam Bachler
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.,Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT - Private University for Health Sciences and Health Technology, Hall i.T., Austria
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