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Jin E, Li B, Wang X, Yan R, Yan C, Gao Y. Prevalence of antiphospholipid antibodies in COVID-19 patients: A meta-analysis. Vascul Pharmacol 2025; 158:107444. [PMID: 39638272 DOI: 10.1016/j.vph.2024.107444] [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: 07/12/2024] [Revised: 11/08/2024] [Accepted: 11/26/2024] [Indexed: 12/07/2024]
Abstract
OBJECTIVE In some reports, antiphospholipid antibodies (aPL) prevalence is higher in COVID-19 patients. This study intended to compare aPL prevalence between COVID-19 patients and healthy controls, and differences in aPL types using meta-analysis. METHODS This work retrieved published literature about association between COVID-19 and aPL from Embase, Web of Science, PubMed, and The Cochrane Library databases. The observation group was COVID-19 patients, and the control group was healthy individuals. Outcome measures contained any of following aPLs: classic aPL: anti-cardiolipin antibodies (aCL) and anti-β2-glycoprotein-1 antibodies (Anti-β2GP1); other non-criteria aPL: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-annexin-V antibodies (AnV). Meta-analysis was done on Review Manager 5.4. RESULTS 10 studies involving 2288 patients were deemed eligible for inclusion. The results of the meta-analysis showed that the prevalence of Classic aPL and Any aPL in the COVID-19 group was significantly higher than in the healthy group (Classic aPL, RR = 2.55, 95 % CI = 1.83-3.55, P < 0.00001; Any aPL, RR = 2.34, 95 % CI = 1.46-3.77, P = 0.0005). Anti-β2GP1 IgA antibodies were the most common aPL in COVID-19 patients, with a significantly higher prevalence than in the healthy group (RR = 4.26, 95 % CI = 2.84-6.40, P < 0.00001). The prevalence of the four types of IgM aPL was significantly higher in the COVID-19 group compared to the healthy group, while there was no significant difference in aPL IgG between the two groups. CONCLUSION The prevalence of aPL in COVID-19 patients was significantly higher than in the healthy control group. IgM aPL was more easily detectable in the early stages of COVID-19 infection, while IgG aPL may be of more concern in the later time points of the immune epidemiology following SARS-CoV-2 infection.
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Affiliation(s)
- Er Jin
- Department of Pulmonary and Critical Care Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310002, Zhejiang Province, China
| | - Bei Li
- Department of Geriatric, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
| | - Xiaonan Wang
- Department of Geriatric, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
| | - Runlan Yan
- Department of Geriatric, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China
| | - Chenhong Yan
- Department of Pulmonary and Critical Care Medicine, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310002, Zhejiang Province, China
| | - Yue Gao
- Department of Geriatric, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, Zhejiang Province, China; Zhejiang Provincial Key laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Major Chronic Disease in the Elderly, Hangzhou 310006, Zhejiang Province, China.
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Yang S, Sun Q, Yuan X, Wang J, Wang H, Hu W, Peng Q, Zhang C, Li X, Huang W, Xie J, Guo F, Liu L, Yang Y, Huang Y. Effect of prone position on ventilation-perfusion matching in patients with moderate to severe ARDS with different clinical phenotypes. Respir Res 2025; 26:70. [PMID: 40022116 PMCID: PMC11871685 DOI: 10.1186/s12931-025-03154-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 02/13/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND ARDS is a heterogeneous syndrome involving different subphenotypes with different clinical features and different responses to treatment strategies. The prone position (PP) is an effective treatment for ARDS; however, whether the effects of prone positioning vary among ARDS patients with different subphenotypes remains unknown. OBJECTIVES To evaluated the impact of PP on ventilation-perfusion matching(VQ matching) by contrast-enhanced Electrical impedance tomography (EIT) in ARDS patients with different subphenotypes. METHODS This was a prospective, observational study at the medical ICU of Zhongda Hospital, Southeast University. ARDS patients undergoing mechanical ventilation were screened and allocated to different subphenotypes based on lung morphology (focal/non-focal) and D-dimer level (low/high D-dimer). EIT was used in the supine position and 3 h, 6 h, and 12 h after the PP during the first PP session. RESULTS From July 1, 2021, to July 1, 2022, 25 patients were included in this study. 10 patients (40%) were focal ARDS, and 15 were non-focal ARDS based on baseline morphology. 12 patients (48%) were high D-dimer ARDS, and 13 were low D-dimer ARDS based on baseline D-dimer levels. PaO2/FiO2 increased significantly 3 h after prone positioning in focal ARDS patients (130.30[109.94-147.30] vs. 213.50[176.00-256.50] mmHg, p < 0.001), while the effect of improved oxygenation was not apparent until 6 h after prone positioning in non-focal ARDS patients (104.60[95.20-127.00] vs. 190.20[160.10-213.20] mm Hg, p < 0.001). VQ matching improved after 3 h in the prone position in the focal ARDS group (69.93 ± 6.69 vs. 78.22 ± 5.07, p = 0.006) but improved after only 6 h in the prone position in the non-focal ARDS group (67.32 ± 4.78 vs. 78.70 ± 5.93, p < 0.001). In ARDS patients with varying levels of D-dimer, increased PaO2/FiO2 (126.60[99.30-146.20] vs. 185.20[112.10-236.00] mmHg, p = 0.013) and improved VQ matching (67.60 ± 4.60 vs. 72.97 ± 6.48, p = 0.023) were observed at 3 h in the PP in patients with low D-dimer ARDS. In contrast, increased PaO2/FiO2(105.20[95.20-124.10] vs. 195.2[183.20-213.20], p < 0.001) and improved VQ matching (67.19 ± 6.70 vs. 72.50 ± 6.37, p < 0.001) were revealed only after 6 h in the prone position in high D-dimer ARDS patients. CONCLUSIONS For moderate to severe ARDS patients, non-focal and high D-dimer ARDS patients need longer PP to improve oxygenation and VQmatching than the focal and low D-dimer patients. CLINICAL TRIAL REGISTRATION This was a prospective, observational study registered in the Chinese Clinical Trial Registry (ChiCTR2200055442, https://www.chictr.org.cn/ ), on June 30, 2021.
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Affiliation(s)
- Shuhe Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Qin Sun
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xueyan Yuan
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Jinlong Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Haofei Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Wenhan Hu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Qingyun Peng
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Chen Zhang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xiangquan Li
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Wei Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Jianfeng Xie
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Fengmei Guo
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Ling Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Yi Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Yingzi Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
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Anaya BJ, D'Angelo D, Bettini R, Molina G, Sanz-Perez A, Dea-Ayuela MA, Galiana C, Rodríguez C, Tirado DF, Lalatsa A, González-Burgos E, Serrano DR. Heparin-azithromycin microparticles show anti-inflammatory effects and inhibit SARS-CoV-2 and bacterial pathogens associated to lung infections. Carbohydr Polym 2025; 348:122930. [PMID: 39567148 DOI: 10.1016/j.carbpol.2024.122930] [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: 08/05/2024] [Revised: 10/23/2024] [Accepted: 10/27/2024] [Indexed: 11/22/2024]
Abstract
Pulmonary infections are a leading cause of morbidity and mortality worldwide, a situation exacerbated by the COVID-19. Azithromycin (AZM) is used orally to treat pulmonary infections due to its ability to accumulate in lung tissues and immune cells after oral administration. Sulfated polysaccharides, such as heparin, are known to inhibit SARS-CoV-2 entry. This study presents a novel approach focused on developing a dry powder inhaler of AZM-loaded microparticles composed of either heparin or its derivatives. The microparticle formulations exhibited potent antiviral activity against SARS-CoV-2 (IC50 ≤ 95 nM) while retaining superior antibacterial efficacy against Streptococcus pneumoniae and Pseudomonas aeruginosa compared to free AZM (MIC ≤15 μg/mL). Importantly, at bactericidal concentrations, no cytotoxic effects were observed on mammalian cells, including Calu-3 cells and red blood cells. The formulations demonstrated effective alveolar aerodynamic deposition (MMAD ranging from 1 μm to 3 μm) with a Fine Particle Fraction below 5 μm close to 50 %. Adopting a conservative estimate of 20 mL for the pulmonary epithelial lining fluid volume in healthy adults, efficacious local concentrations of sulfated polysaccharides and AZM would be delivered to the lung using this multifaceted strategy which holds promise for the treatment of bacterial pulmonary infections associated with COVID-19.
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Affiliation(s)
- Brayan J Anaya
- Pharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
| | - Davide D'Angelo
- Food and Drug Department, University of Parma, Parco Area delle Scienze 27a, 43124 Parma, Italy
| | - Ruggero Bettini
- Food and Drug Department, University of Parma, Parco Area delle Scienze 27a, 43124 Parma, Italy
| | - Gracia Molina
- Pharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
| | - Amadeo Sanz-Perez
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain
| | | | - Carolina Galiana
- Department of Pharmacy, Universidad Cardenal Herrera-CEU, CEU Universitites, Valencia, Spain
| | - Carmina Rodríguez
- Department of Microbiology and Parasitology, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain
| | - Diego F Tirado
- Dirección Académica, Universidad Nacional de Colombia, Sede de La Paz, La Paz 202017, Colombia
| | - Aikaterini Lalatsa
- CRUK Formulation Unit, School of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnot Building, Robertson Wing, 161 Cathedral St, Glasgow G4 0RE, UK
| | - Elena González-Burgos
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain.
| | - Dolores R Serrano
- Pharmaceutics and Food Technology Department, Faculty of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain.
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Zhang X, Fang K, Lan D, Huang X, Ji X, Meng R, Zhou D. Impact of the COVID-19 pandemic on cerebral venous sinus thrombosis in China: a comparative study. BMC Neurol 2025; 25:17. [PMID: 39799313 PMCID: PMC11724590 DOI: 10.1186/s12883-025-04019-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/02/2025] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Cerebral venous sinus thrombosis (CVST) is a rare yet significant neurological disorder with high mortality. Understanding its evolving characteristics, risk factors, and outcomes, particularly in Chinese patients after the COVID-19 pandemic, is critical for developing effective preventive and therapeutic strategies. METHODS A retrospective analysis was conducted on 471 CVST cases from Xuanwu Hospital, comparing data before (2013-2017, n = 243) and after (2021-2023, n = 228) the COVID-19 pandemic. Data on demographics, clinical features, risk factors, and outcomes were evaluated, with subgroup analyses based on gender and age. RESULTS The mean patient age was 38 ± 14 years, with a female preponderance (55.0%). After the COVID-19 pandemic, significant changes in symptoms and neuroimaging findings were observed, including increased visual impairment and decreased headache, neurological deficits, and seizures. Infection emerged as a prominent risk factor, including eight cases related to COVID-19 or vaccination. At discharge, favorable outcomes (mRS 0-2) were noted in 86.6% of patients. Poor outcomes were associated with central nervous system (CNS) infection, oral contraceptive use or hormone replacement therapy (HRT), hematologic disorders, anemia, and prothrombotic conditions. Anemia was identified as an independent predictor of survival. CONCLUSIONS The pandemic has significantly altered the clinical and epidemiological profile of CVST in China. Infections have emerged as key risk factors, while anemia remains a critical prognostic indicator. These findings highlight the need for targeted clinical strategies to improve outcomes. TRIAL REGISTRATION This study protocol was reviewed and approved by the ethics committee of Xuanwu Hospital, Capital Medical University (No. 2022-004, dated on November 20, 2022). The clinical trial was registered at Chinese Clinical Trial Registry (ChiCTR2200057621).
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Affiliation(s)
- Xiaoming Zhang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Kun Fang
- Capital Medical University, Beijing, 100069, China
| | - Duo Lan
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Xiangqian Huang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Xunming Ji
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Ran Meng
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China.
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
| | - Da Zhou
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, 100053, China.
- National Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
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Wen K, Lin Z, Tan H, Han M. Correlations between coagulation abnormalities and inflammatory markers in trauma-induced coagulopathy. Front Physiol 2024; 15:1474707. [PMID: 39539951 PMCID: PMC11557354 DOI: 10.3389/fphys.2024.1474707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 09/30/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction In multiple trauma patients, the occurrence of trauma-induced coagulopathy (TIC) is closely associated with tissue damage and coagulation function abnormalities in the pathophysiological process. Methods This study established a multiple trauma and shock model in Sprague-Dawley (SD) rats and comprehensively utilized histological staining and radiographic imaging techniques to observe injuries in the intestine, liver, skeletal muscles, and bones. Monitoring activated partial thromboplastin time (APTT), platelet (PLT) count, respiratory rate, blood pressure, and other physiological indicators revealed time-dependent alterations in coagulation function and physiological indicators. Enzyme-linked immunosorbent assay (ELISA) measurements of inflammatory factors Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6) and vascular endothelial injury marker (Syndecan-1) were also conducted. Results Experimental results demonstrated significant changes in tissue structure after multiple traumas, although widespread necrosis or hemorrhagic lesions were not observed. There were time-dependent alterations in coagulation function and physiological indicators. ELISA measurements showed a strong positive correlation between the significant decrease in PLT count and the increase in TNF-α and IL-6 concentrations. Discussion The study provides crucial information for the early diagnosis and treatment of TIC. The findings suggest that structured monitoring of coagulation and inflammatory indicators can help in understanding the pathophysiological changes and aid in the management of TIC in multiple trauma patients.
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Affiliation(s)
- Ke Wen
- Department of Hand and Microsurgery, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, Hubei, China
| | - Zhexuan Lin
- Bio-Analytical Laboratory of Shantou University Medical College, Shantou, China
| | - Haizhu Tan
- Department of Preventive Medicine, Shantou University Medical College, Shantou, China
| | - Ming Han
- Emergency Department of Shenzhen University General Hospital, Shenzhen, China
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Chacko RK, Narendran S, Kumar K, Shah VM. Changing trend in the etiology of papilledema during the COVID-19 pandemic in India. Indian J Ophthalmol 2024; 72:1524-1525. [PMID: 39331448 PMCID: PMC11573017 DOI: 10.4103/ijo.ijo_626_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024] Open
Affiliation(s)
- Ruhel Kurudamannil Chacko
- Department of Neuro-Ophthalmology, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Siddharth Narendran
- Aravind Medical Research Foundation, Madurai and Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Karthik Kumar
- Department of Neuro-Ophthalmology, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
| | - Virna M Shah
- Department of Neuro-Ophthalmology, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Coimbatore, Tamil Nadu, India
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Noone D, Preston RJS, Rehill AM. The Role of Myeloid Cells in Thromboinflammatory Disease. Semin Thromb Hemost 2024; 50:998-1011. [PMID: 38547918 DOI: 10.1055/s-0044-1782660] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Inflammation contributes to the development of thrombosis, but the mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, and represent an important host defense mechanism to limit pathogen spread in the bloodstream. However, dysregulated proinflammatory activity is implicated in the progression of venous thromboembolism and arterial thrombosis. In this review, we focus on the role of myeloid cells in propagating thromboinflammation in acute inflammatory conditions, such as sepsis and coronavirus disease 2019 (COVID-19), and chronic inflammatory conditions, such as obesity, atherosclerosis, and inflammatory bowel disease. Myeloid cells are considered key drivers of thromboinflammation via upregulated tissue factor activity, formation of neutrophil extracellular traps (NETs), contact pathway activation, and aberrant coagulation factor-mediated protease-activated receptor (PAR) signaling. We discuss how strategies to target the intersection between myeloid cell-mediated inflammation and activation of blood coagulation represent an exciting new approach to combat immunothrombosis. Specifically, repurposed anti-inflammatory drugs, immunometabolic regulators, and NETosis inhibitors present opportunities that have the potential to dampen immunothrombotic activity without interfering with hemostasis. Such therapies could have far-reaching benefits for patient care across many thromboinflammatory conditions.
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Affiliation(s)
- David Noone
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
| | - Roger J S Preston
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
| | - Aisling M Rehill
- Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
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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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Guitouni A, Belacel N, Benabbou L, Moa B, Erman M, Abdul H. Longitudinal bi-criteria framework for assessing national healthcare responses to pandemic outbreaks. Sci Rep 2024; 14:22109. [PMID: 39333580 PMCID: PMC11436803 DOI: 10.1038/s41598-024-69212-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 08/01/2024] [Indexed: 09/29/2024] Open
Abstract
Pandemics like COVID-19 have illuminated the significant disparities in the performance of national healthcare systems (NHCSs) during rapidly evolving crises. The challenge of comparing NHCS performance has been a difficult topic in the literature. To address this gap, our study introduces a bi-criteria longitudinal algorithm that merges fuzzy clustering with Data Envelopment Analysis (DEA). This new approach provides a comprehensive and dynamic assessment of NHCS performance and efficiency during the early phase of the pandemic. By categorizing each NHCS as an efficient performer, inefficient performer, efficient underperformer, or inefficient underperformer, our analysis vividly represents performance dynamics, clearly identifying the top and bottom performers within each cluster of countries. Our methodology offers valuable insights for performance evaluation and benchmarking, with significant implications for enhancing pandemic response strategies. The study's findings are discussed from theoretical and practical perspectives, offering guidance for future health system assessments and policy-making.
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Affiliation(s)
- Adel Guitouni
- Gustavson School of Business, University of Victoria, Victoria, BC, Canada.
| | - Nabil Belacel
- Digital Technologies Research Center, National Research Council, Ottawa, ON, Canada.
| | - Loubna Benabbou
- Department of Management Sciences, Universite du Quebec a Rimouski, Rimouski, QC, Canada
| | - Belaid Moa
- Advanced Computing, University of Victoria, Victoria, BC, Canada
| | - Munire Erman
- Respiratory Therapy, Medical Day Care, Cancer Care, Social Work, Maternity and Pediatrics Units, Campbell River General Hospital, Campbell River, BC, Canada
| | - Halim Abdul
- Department of Economics, University of Victoria, Victoria, BC, Canada
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El Hajra I, Llop E, Blanco S, Perelló C, Fernández-Carrillo C, Calleja JL. Portal Vein Thrombosis in COVID-19: An Underdiagnosed Disease? J Clin Med 2024; 13:5599. [PMID: 39337086 PMCID: PMC11433429 DOI: 10.3390/jcm13185599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Background: Multiple studies have linked COVID-19 to a higher incidence of thromboembolic disorders. However, the association of COVID-19 with other potentially life-threatening complications, such as splanchnic vein thrombosis, is less well understood. This study aims to assess the prevalence, patient characteristics, clinical presentation, and outcomes of patients with portal vein thrombosis (PVT) and COVID-19. Methods: This was a retrospective observational study. From all positive patients for a reverse-transcription polymerase chain reaction (RT-PCR) swab test from March 2020 to June 2020, we included those who were older than 18 years, had received abdominal contrast-enhanced computed tomography (CT) in the 6 months following the positive RT-PCR swab, and had no previously known splanchnic vein thrombosis. Results: A total of 60 patients with abdominal CT were selected from all those positive for SARS-CoV-2 (n = 2987). The prevalence of PVT was 3/60 (5%). The mean age was 66.1 ± 16.5 years and 51.7% were male. In two of the three patients, there was no underlying pathology as a risk factor for PVT and one of them presented cirrhosis. The number of days from the start of COVID-19 symptoms until the PVT diagnosis were 21, 12, and 10 days. Anticoagulation treatment achieved recanalization in 100% of cases. During a mean follow-up of 803 days, none of the patients experienced long-term complications. Conclusions: Portal vein thrombosis is uncommon, and its incidence may be higher in COVID-19 patients. A greater understanding of the features of this disease in the context of COVID-19 could aid towards its diagnosis and allow for early detection and management.
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Affiliation(s)
- Ismael El Hajra
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
| | - Elba Llop
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
- Instituto de Investigación Sanitaria Puerta Hierro-Segovia Arana (IDIPHISA) Majadahonda, 28222 Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBEREHD), 28029 Madrid, Spain
| | - Santiago Blanco
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
| | - Christie Perelló
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
- Instituto de Investigación Sanitaria Puerta Hierro-Segovia Arana (IDIPHISA) Majadahonda, 28222 Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBEREHD), 28029 Madrid, Spain
| | - Carlos Fernández-Carrillo
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
- Instituto de Investigación Sanitaria Puerta Hierro-Segovia Arana (IDIPHISA) Majadahonda, 28222 Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBEREHD), 28029 Madrid, Spain
| | - José Luis Calleja
- Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain
- Instituto de Investigación Sanitaria Puerta Hierro-Segovia Arana (IDIPHISA) Majadahonda, 28222 Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBEREHD), 28029 Madrid, Spain
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11
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Favatella N, Dalton D, Byon W, Merali SJ, Klem C. Clinical Implications of Co-administering Apixaban with Key Interacting Medications. Clin Pharmacol Drug Dev 2024; 13:961-973. [PMID: 39046333 DOI: 10.1002/cpdd.1446] [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: 03/23/2023] [Accepted: 06/17/2024] [Indexed: 07/25/2024]
Abstract
With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P‑glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.
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12
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Deora N, Venkatraman K. Potential use of plant-based therapeutics for the management of SARS-COV2 infection in diabetes mellitus – a review. J Herb Med 2024; 47:100923. [DOI: 10.1016/j.hermed.2024.100923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Pradana ANK, Akahoshi T, Guo J, Mizuta Y, Matsunaga S, Narahara S, Murata M, Yamaura K. CHANGES OF HISTIDINE-RICH GLYCOPROTEIN LEVELS IN CRITICALLY ILL SEPTIC PATIENTS. Shock 2024; 62:351-356. [PMID: 38935033 PMCID: PMC11460739 DOI: 10.1097/shk.0000000000002406] [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: 03/08/2024] [Revised: 04/02/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024]
Abstract
ABSTRACT Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 μg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management.
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Affiliation(s)
- Ayu Nabila Kusuma Pradana
- Department of Advanced Emergency and Disaster medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomohiko Akahoshi
- Department of Advanced Emergency and Disaster medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jie Guo
- Department of Advanced Emergency and Disaster medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yukie Mizuta
- Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shuntaro Matsunaga
- Department of Advanced Emergency and Disaster medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Sayoko Narahara
- Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan
| | - Masaharu Murata
- Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan
| | - Ken Yamaura
- Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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14
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Sato L, Iwamoto N, Kakumoto Y, Tsuzuki S, Togano T, Ishikane M, Okumura N, Yamada G, Inada M, Suzuki T, Hojo M, Takasaki J, Sasaki R, Kimura A, Teruya K, Okamoto T, Hayakawa K, Hara H, Iseki K, Ohmagari N. Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan. J Atheroscler Thromb 2024; 31:1179-1193. [PMID: 38355124 PMCID: PMC11300674 DOI: 10.5551/jat.64448] [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: 06/30/2023] [Accepted: 01/03/2024] [Indexed: 02/16/2024] Open
Abstract
AIM Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P<.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P<.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.
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Affiliation(s)
- Lubna Sato
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- Department of Emergency and Critical Care Medicine, Fukushima Medical University, Fukushima, Japan
| | - Noriko Iwamoto
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yuko Kakumoto
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shinya Tsuzuki
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tomiteru Togano
- Department of Hematology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masahiro Ishikane
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Nobumasa Okumura
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Gen Yamada
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Makoto Inada
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tetsuya Suzuki
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masayuki Hojo
- Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan
| | - Jin Takasaki
- Department of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan
| | - Ryo Sasaki
- Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan
| | - Akio Kimura
- Department of Emergency Medicine and Critical Care, National Center for Global Health and Medicine, Tokyo, Japan
| | - Katsuji Teruya
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tatsuya Okamoto
- Department of Intensive Care Medicine, National Center for Global Health and Medicine, Tokyo, Japan
| | - Kayoko Hayakawa
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hisao Hara
- Department of Cardiology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Ken Iseki
- Department of Emergency and Critical Care Medicine, Fukushima Medical University, Fukushima, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- AMR Clinical Reference Center, National Center for Global Health and Medicine, Tokyo, Japan
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15
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Jiang H, Cao Z, Liu L, Huang Y. Effect of COVID-19 on Thrombosis Incidence and Patient Prognosis in Kidney Transplant Recipients. Med Sci Monit 2024; 30:e944285. [PMID: 38946121 PMCID: PMC11305100 DOI: 10.12659/msm.944285] [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: 02/27/2024] [Accepted: 05/14/2024] [Indexed: 07/02/2024] Open
Abstract
BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.
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Affiliation(s)
- Hao Jiang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
| | - Zhijun Cao
- Department of Urology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou, Jiangsu, PR China
| | - Li Liu
- Intensive Care Unit of the Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
| | - Yuhua Huang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China
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16
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Padín JF, Pérez-Ortiz JM, Redondo-Calvo FJ. Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions. Int J Mol Sci 2024; 25:7209. [PMID: 39000315 PMCID: PMC11241800 DOI: 10.3390/ijms25137209] [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: 05/27/2024] [Revised: 06/25/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.
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Affiliation(s)
- Juan-Fernando Padín
- Department of Medical Sciences, School of Medicine at Ciudad Real, University of Castilla-La Mancha, 13971 Ciudad Real, Spain
| | - José Manuel Pérez-Ortiz
- Facultad HM de Ciencias de la Salud, Universidad Camilo José Cela, 28692 Madrid, Spain
- Instituto de Investigación Sanitaria HM Hospitales, 28015 Madrid, Spain
| | - Francisco Javier Redondo-Calvo
- Department of Medical Sciences, School of Medicine at Ciudad Real, University of Castilla-La Mancha, 13971 Ciudad Real, Spain
- Department of Anaesthesiology and Critical Care Medicine, University General Hospital, 13005 Ciudad Real, Spain
- Translational Research Unit, University General Hospital and Research Institute of Castilla-La Mancha (IDISCAM), 13005 Ciudad Real, Spain
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17
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Pottecher J, Raffi F, Jandrot-Perrus M, Binay S, Comenducci A, Desort-Henin V, François D, Gharakhanian S, Labart M, Meilhoc A, Toledano E, Pletan Y, Avenard G, Sato VH, the GARDEN Investigators. Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial. PLoS One 2024; 19:e0302897. [PMID: 38885234 PMCID: PMC11182546 DOI: 10.1371/journal.pone.0302897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 04/11/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets. METHODS AND PATIENTS GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population. RESULTS Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively. CONCLUSIONS Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE: NCT05070260) and cardiovascular indications.
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Affiliation(s)
- Julien Pottecher
- Strasbourg University Hospital, UR3072, FHU OMICARE, FMTS, Strasbourg, France
| | - Francois Raffi
- Nantes Université, CHU Nantes, INSERM, Department of Infectious Diseases, CIC 1413, Nantes, France
| | | | | | | | | | | | - Shahin Gharakhanian
- Acticor-Biotech, Paris, France
- Shahin Gharakhanian MD Consulting LLC, Cambridge Innovation Center, Cambridge, MA, United States of America
| | | | | | | | | | | | - Victor H. Sato
- International Research Center, Hospital Alemão Oswaldo Cruz, Sao Paulo, Brazil
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18
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Williams B, Zou L, Pittet JF, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesth Analg 2024; 138:696-711. [PMID: 38324297 PMCID: PMC10916756 DOI: 10.1213/ane.0000000000006888] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2023] [Indexed: 02/08/2024]
Abstract
Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients with sepsis and 66% of patients with septic shock, and is often associated with poor clinical outcomes and high mortality. 1 , 2 Recent preclinical and clinical studies have generated new insights into the molecular pathogenesis of SIC. In this article, we analyze the complex pathophysiology of SIC with a focus on the role of procoagulant innate immune signaling in hemostatic activation--tissue factor production, thrombin generation, endotheliopathy, and impaired antithrombotic functions. We also review clinical presentations of SIC, the diagnostic scoring system and laboratory tests, the current standard of care, and clinical trials evaluating the efficacies of anticoagulant therapies.
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Affiliation(s)
- Brittney Williams
- From the Division of Cardiothoracic Anesthesia, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
| | - Lin Zou
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
| | - Jean-Francois Pittet
- Division of Critical Care, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Wei Chao
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
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19
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Wen TZ, Fu WJ, Xiao SQ, Wang S, Li TR, Chen XY, Chen HY, Luo J, Bian XW, Yao XH. Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration. Pathol Res Pract 2024; 256:155251. [PMID: 38490097 DOI: 10.1016/j.prp.2024.155251] [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: 01/15/2024] [Revised: 02/16/2024] [Accepted: 03/04/2024] [Indexed: 03/17/2024]
Abstract
Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.
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Affiliation(s)
- Tian-Zi Wen
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Wen-Juan Fu
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Shi-Qi Xiao
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Shuai Wang
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Tian-Ran Li
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Xin-Yu Chen
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - He-Yuan Chen
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Jie Luo
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
| | - Xiu-Wu Bian
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
| | - Xiao-Hong Yao
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
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20
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Rajan R, Hanifah M, Mariappan V, Anand M, Balakrishna Pillai A. Soluble Endoglin and Syndecan-1 levels predicts the clinical outcome in COVID-19 patients. Microb Pathog 2024; 188:106558. [PMID: 38272329 DOI: 10.1016/j.micpath.2024.106558] [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: 11/02/2023] [Revised: 01/21/2024] [Accepted: 01/22/2024] [Indexed: 01/27/2024]
Abstract
Endothelial instability is reported to be involved in the pathogenesis of COVID-19. The mechanism that regulates the endothelial dysfunction and disease virulence is not known. Studies on proteins that are released into circulation by activated endothelial cells may provide some means to understand the disease manifestation. The study investigated the circulating levels of two molecules Endoglin (Eng) and Syndecan-1 (SDC-1) that are presumed to be involved in the maintenance of endothelial integrity and their association with hypercoagulation marker in COVID-19 patients. The serum levels of Eng, SDC-1, D-mer were evaluated using ELISA at the time of admission (DOA) and day 7 post-admission among COVID-19 patients (N = 39 with 17 moderate and 22 severe cases). Compared to the time of admission, there was an increase in sEng and sSDC1 levels in all COVID-19 cases on day 7 post admission. The serum levels of sEng and sSDC-1 was significantly (P ≤ 0.001 & P ≤ 0.01 respectively) elevated in severe cases including the four deceased group compared to moderate cases on day 7 post admission. Further, the study molecules showed a strong positive association (P ≤ 0.001) with the hypercoagulation marker D-mer. The results show an early shedding of the endothelial proteins sEng and sSDC-1 into circulation as a host response to the viral infection during the febrile phase of infection. Increased levels of sEng and sSDC-1 along with D-mer could be beneficial in predicting COVID-19 disease severity.
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Affiliation(s)
- Remya Rajan
- Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
| | - Mohamed Hanifah
- Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
| | - Vignesh Mariappan
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
| | - Monica Anand
- Department of General Medicine, Mahatma Gandhi Medical College and Research Institute (MGMCRI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
| | - Agieshkumar Balakrishna Pillai
- Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, 607 402, India.
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21
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Kazi S, Othman M, Khoury R, Bernstein PS, Thachil J, Ciantar E, Ferrara L, Netto M, Abdul-Kadir R, Malinowski AK. Report of the ISTH registry on pregnancy and COVID-19-associated coagulopathy (COV-PREG-COAG). Obstet Med 2024; 17:13-21. [PMID: 38660318 PMCID: PMC11037201 DOI: 10.1177/1753495x231206931] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 06/16/2023] [Indexed: 04/26/2024] Open
Abstract
Background Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. Methods An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. Results All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Conclusions Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave.
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Affiliation(s)
- Sajida Kazi
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Maha Othman
- Queen's University, Kingston, Canada
- St. Lawrence College, School of Baccalaureate Nursing, Kingston, Canada
- Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Rasha Khoury
- Divisions of Maternal Fetal Medicine and Complex Family Planning, Boston University School of Medicine, Boston, USA
| | - Peter S Bernstein
- Montefiore Medical Center/Albert Einstein College of Medicine, New York, USA
| | | | - Etienne Ciantar
- Leeds Teaching Hospital NHS Trust, Leeds General Infirmary, Leeds, UK
| | | | | | - Rezan Abdul-Kadir
- The Royal Free NHS Foundation Hospital and Institute for Women's Health, University College London, London, UK
| | - A Kinga Malinowski
- Division of Maternal-Fetal Medicine, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
- University of Toronto, Toronto, Canada
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22
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Baroni M, Beltrami S, Schiuma G, Ferraresi P, Rizzo S, Passaro A, Molina JMS, Rizzo R, Di Luca D, Bortolotti D. In Situ Endothelial SARS-CoV-2 Presence and PROS1 Plasma Levels Alteration in SARS-CoV-2-Associated Coagulopathies. Life (Basel) 2024; 14:237. [PMID: 38398746 PMCID: PMC10890393 DOI: 10.3390/life14020237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Coagulation decompensation is one of the complications most frequently encountered in COVID-19 patients with a poor prognosis or long-COVID syndrome, possibly due to the persistence of SARS-CoV-2 infection in the cardiovascular system. To date, the mechanism underlying the alteration of the coagulation cascade in COVID-19 patients remains misunderstood and the anticoagulant protein S (PROS1) has been described as a potential risk factor for complications related to COVID-19, due to PLpro SARS-CoV-2 enzyme proteolysis. METHODS Biopsies and blood samples were collected from SARS-CoV-2 positive and negative swab test subjects with coagulopathies (peripheral arterial thrombosis), and SARS-CoV-2 presence, ACE2 and CD147 expression, and plasmatic levels of PROS1 were evaluated. RESULTS We reported a significant decrease of plasmatic PROS1 in the coagulopathic SARS-CoV-2 swab positive cohort, in association with SARS-CoV-2 in situ infection and CD147 peculiar expression. These data suggested that SARS-CoV-2 associated thrombotic/ischemic events might involve PROS1 cleavage by viral PLpro directly in the site of infection, leading to the loss of its anticoagulant function. CONCLUSIONS Based on this evidence, the identification of predisposing factors, such as CD147 increased expression, and the use of PLpro inhibitors to preserve PROS1 function, might be useful for COVID-19 coagulopathies management.
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Affiliation(s)
- Marcello Baroni
- Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, 44121 Ferrara, Italy; (M.B.); (P.F.)
| | - Silvia Beltrami
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
| | - Giovanna Schiuma
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
| | - Paolo Ferraresi
- Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, 44121 Ferrara, Italy; (M.B.); (P.F.)
| | - Sabrina Rizzo
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
| | - Angelina Passaro
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy;
| | - Juana Maria Sanz Molina
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
| | - Roberta Rizzo
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
| | - Dario Di Luca
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy;
| | - Daria Bortolotti
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy; (S.B.); (G.S.); (S.R.); (J.M.S.M.); (D.B.)
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23
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Dembinski R. [ARDS Diagnostics and Treatment after the Coronavirus Pandemic - Everything as it was?]. Anasthesiol Intensivmed Notfallmed Schmerzther 2024; 59:24-33. [PMID: 38190823 DOI: 10.1055/a-2043-8628] [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: 01/10/2024]
Abstract
ARDS is a syndrome that can develop as a result of various underlying diseases. For a long time, the prevailing belief was that the course of the disease was comparable regardless of the underlying disease. However, even before the COVID-19 pandemic, it was suspected that there were different manifestations that could be treated more individually and thus reduce the high mortality rate of ARDS, which has remained unchanged for years. The various findings on the heterogeneity of the course of the disease in COVID-related ARDS appear to confirm these assumptions. It is therefore to be expected that the diagnosis and treatment of non-COVID-related ARDS will also have to be individualised according to such phenotypes in the future. However, as long as the effectiveness of such strategies has not been proven in clinical trials, the current recommendations for ARDS therapy will remain valid for the time being. However, the adjustments already formulated in this context to individual pathophysiological conditions with regard to respiratory mechanics, ventilation-perfusion distribution and possible cardiac dysfunction should be made more meticulously than has usually been the case to date.
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24
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Korosoglou G, Mouselimis D, Koenig E, Konstantinides S. Ultrasound-assisted catheter-directed thrombolysis in a patient with COVID-19 infection and bilateral intermediate-to-high-risk pulmonary embolism: a case report. Eur Heart J Case Rep 2024; 8:ytad628. [PMID: 38223512 PMCID: PMC10787366 DOI: 10.1093/ehjcr/ytad628] [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: 02/20/2023] [Revised: 09/28/2023] [Accepted: 12/13/2023] [Indexed: 01/16/2024]
Abstract
Background Acute pulmonary embolism (PE) is a common cardiovascular disorder, potentially associated with high morbidity and mortality rates. Case summary Herein, we report on a patient with COVID-19 infection and bilateral PE, who presented after cardiovascular resuscitation with return of spontaneous circulation. Initially, an acute coronary syndrome was suspected but bedside echocardiography showed dilatation of the right ventricle (RV) and RV dysfunction, helping to establish the diagnosis of acute intermediate-to-high-risk PE, which was subsequently confirmed by contrast-enhanced computed tomography pulmonary angiography. The patient was successfully treated using low-dose (12 mg of tissue plasminogen) ultrasound-assisted catheter-directed thrombolysis, which resulted in prompt clinical improvement and reversal of RV dysfunction without bleeding complications. Discussion This case demonstrates the importance of echocardiography for the differential diagnosis of PE and of catheter-directed thrombolysis for its treatment in patients with intermediate-to-high-risk and high-risk PEs.
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Affiliation(s)
- Grigorios Korosoglou
- Department of Cardiology, GRN Hospital Weinheim, Vascular Medicine & Pneumology, Röntgenstrasse 1, 69469 Weinheim, Germany
- Weinheim Imaging Center, Hector Foundation, Röntgenstrasse 1, 69469 Weinheim, Germany
| | - Dimitrios Mouselimis
- Department of Cardiology, GRN Hospital Weinheim, Vascular Medicine & Pneumology, Röntgenstrasse 1, 69469 Weinheim, Germany
- Weinheim Imaging Center, Hector Foundation, Röntgenstrasse 1, 69469 Weinheim, Germany
| | - Elke Koenig
- Department of Anesthesiology and Intensive Care Medicine, GRN Hospital Weinheim, Weinheim, Germany
| | - Stavros Konstantinides
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
- Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece
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25
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Mendoza RP, Momeni A, Saha N, Arshi J, Gabutan EC, Alejandro N, Zuretti A, Premsrirut PK, Nikolov DB. The Angiopoietin Signaling Pathway Is Involved in Inflammatory Processes in Hospitalized COVID-19 Patients. Microorganisms 2023; 11:2940. [PMID: 38138084 PMCID: PMC10745910 DOI: 10.3390/microorganisms11122940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/03/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
The viral agent SARS-CoV-2 clearly affects several organ systems, including the cardiovascular system. Angiopoietins are involved in vascular integrity and angiogenesis. Angiopoietin-1 (Ang1) promotes vessel stabilization, while angiopoietin-2 (Ang2), which is usually expressed at low levels, is significantly elevated in inflammatory and angiogenic conditions. Interleukin-6 (IL-6) is known to induce defective angiogenesis via the activation of the Ang2 pathway. Vasculitis and vasculopathy are some of the defining features of moderate to severe COVID-19-associated systemic disease. We investigated the serum levels of angiopoietins, as well as interleukin-6 levels and anti-SARS-CoV2 IgG titers, in hospitalized COVID-19 patients across disease severity and healthy controls. Ang2 levels were elevated in COVID-19 patients across all severity compared to healthy controls, while Ang1 levels were decreased. The patients with adverse outcomes (death and/or prolonged hospitalization) had relatively lower and stable Ang1 levels but continuously elevated Ang2 levels, while those who had no adverse outcomes had increasing levels of both Ang1 and Ang2, followed by a decrease in both. These results suggest that the dynamic levels of Ang1 and Ang2 during the clinical course may predict adverse outcomes in COVID-19 patients. Ang1 seems to play an important role in controlling Ang2-related inflammatory mechanisms in COVID-19 patients. IL-6 and anti-SARS-CoV2 spike protein IgG levels were significantly elevated in patients with severe disease. Our findings represent an informative pilot assessment into the role of the angiopoietin signaling pathway in the inflammatory response in COVID-19.
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Affiliation(s)
- Rachelle P. Mendoza
- Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA;
| | - Amir Momeni
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA;
| | - Nayanendu Saha
- Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA;
| | - Juwairiya Arshi
- Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA;
| | - Elmer C. Gabutan
- Department of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA; (E.C.G.); (A.Z.)
| | - Nichole Alejandro
- Bouvé College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA;
| | - Alejandro Zuretti
- Department of Pathology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA; (E.C.G.); (A.Z.)
| | - Prem K. Premsrirut
- Department of Cell Biology, SUNY Downstate Health Sciences University, 450 Clarkson Avenue, Brooklyn, NY 11203, USA;
- Mirimus Inc., 760 Parkside Ave, Brooklyn, NY 11226, USA
| | - Dimitar B. Nikolov
- Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA;
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26
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Harte JV, Coleman-Vaughan C, Crowley MP, Mykytiv V. It's in the blood: a review of the hematological system in SARS-CoV-2-associated COVID-19. Crit Rev Clin Lab Sci 2023; 60:595-624. [PMID: 37439130 DOI: 10.1080/10408363.2023.2232010] [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: 04/10/2023] [Accepted: 06/27/2023] [Indexed: 07/14/2023]
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global healthcare crisis. While SARS-CoV-2-associated COVID-19 affects primarily the respiratory system, patients with COVID-19 frequently develop extrapulmonary manifestations. Notably, changes in the hematological system, including lymphocytopenia, neutrophilia and significant abnormalities of hemostatic markers, were observed early in the pandemic. Hematological manifestations have since been recognized as important parameters in the pathophysiology of SARS-CoV-2 and in the management of patients with COVID-19. In this narrative review, we summarize the state-of-the-art regarding the hematological and hemostatic abnormalities observed in patients with SARS-CoV-2-associated COVID-19, as well as the current understanding of the hematological system in the pathophysiology of acute and chronic SARS-CoV-2-associated COVID-19.
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Affiliation(s)
- James V Harte
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
- School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland
| | | | - Maeve P Crowley
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
- Irish Network for Venous Thromboembolism Research (INViTE), Ireland
| | - Vitaliy Mykytiv
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
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27
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Wu J, Cao B, Liao J, Li Y, Lu G, Gong F, Lin G, Zhao M. Navigation of Knowledge: the Impact of COVID-19 on Pregnancy-a Bibliometric Analysis. Reprod Sci 2023; 30:3548-3562. [PMID: 37488404 DOI: 10.1007/s43032-023-01312-x] [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: 04/28/2023] [Accepted: 07/14/2023] [Indexed: 07/26/2023]
Abstract
Since the outbreak of COVID-19, countries around the world have faced huge economic and social burdens. SARS-COV-2 may exist in nature for a long time due to the diversity of its different variants. Pregnant women and newborns as vulnerable groups will suffer serious health threats. Bibliometrics as a method of summarizing publications can be used to extract important achievements and hot topics in this field. We search the target publications from the Web of Science Core collection database, and then use Microsoft Office Excel, CiteSpace, R, Scimago, and VOSviewer for visual analysis. Finally, we included 1709 publications from 2998 institutions in 104 countries. The number of publications has exploded since the COVID-19 pandemic in 2019. Among them, the USA, China, Britain, and Italy have higher quantity and quality. We identified important journals, authors, keywords, and references in this field. Anxiety, stress, risk of pregnancy complications, and vaccine safety and acceptance have received extensive attention from scholars during the COVID-19 pandemic and will continue to be urgent issues to be addressed in the future. Most of the current studies fall into the category of case reports and clinical data analysis. COVID-19 has been linked to serious pregnancy complications and mental illness, and vaccination during pregnancy is recommended to protect both mother and fetus. Further large-scale cohort studies and discovery of molecular mechanisms are needed in this field.
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Affiliation(s)
- Jingrouzi Wu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
| | - Buzi Cao
- Hunan Normal University School of Medicine, Changsha, Hunan, China
| | - Jingnan Liao
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
| | - Yuan Li
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
| | - Guangxiu Lu
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
| | - Fei Gong
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China
| | - Ge Lin
- Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, China.
- Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
| | - Mingyi Zhao
- Pediatric Department of the 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.
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28
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Petramala L, Sarlo F, Servello A, Baroni S, Suppa M, Circosta F, Galardo G, Gandini O, Marino L, Cavallaro G, Iannucci G, Concistrè A, Letizia C. Pulmonary embolism post-Covid-19 infection: physiopathological mechanisms and vascular damage biomarkers. Clin Exp Med 2023; 23:4871-4880. [PMID: 37537404 PMCID: PMC10725340 DOI: 10.1007/s10238-023-01150-w] [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: 05/06/2023] [Accepted: 07/22/2023] [Indexed: 08/05/2023]
Abstract
Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index. Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2).
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Affiliation(s)
- Luigi Petramala
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Francesca Sarlo
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy
| | - Adriana Servello
- Emergency Medicine Unit, Department of Emergency-Acceptance, Critical Areas and Trauma, Policlinico "Umberto I", Rome, Italy
| | - Silvia Baroni
- Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marianna Suppa
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy
| | - Francesco Circosta
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
| | - Gioacchino Galardo
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy
| | - Orietta Gandini
- Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Luca Marino
- UOC Chimica, Biochimica e Biologia Molecolare Clinica, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy.
- Department of Mechanical and Aerospace Engineering, "Sapienza" University of Rome, Rome, Italy.
| | - Giuseppe Cavallaro
- Department of Surgery Pietro Valdoni, Sapienza" University of Rome, Rome, Italy
| | - Gino Iannucci
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
| | - Antonio Concistrè
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
| | - Claudio Letizia
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, Rome, Italy
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Liontos A, Biros D, Matzaras R, Tsarapatsani KH, Kolios NG, Zarachi A, Tatsis K, Pappa C, Nasiou M, Pargana E, Tsiakas I, Lymperatou D, Filippas-Ntekouan S, Athanasiou L, Samanidou V, Konstantopoulou R, Vagias I, Panteli A, Milionis H, Christaki E. Inflammation and Venous Thromboembolism in Hospitalized Patients with COVID-19. Diagnostics (Basel) 2023; 13:3477. [PMID: 37998613 PMCID: PMC10670045 DOI: 10.3390/diagnostics13223477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 11/04/2023] [Accepted: 11/17/2023] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND A link between inflammation and venous thromboembolism (VTE) in COVID-19 disease has been suggested pathophysiologically and clinically. The aim of this study was to investigate the association between inflammation and disease outcomes in adult hospitalized COVID-19 patients with VTE. METHODS This was a retrospective observational study, including quantitative and qualitative data collected from COVID-19 patients hospitalized at the Infectious Diseases Unit (IDU) of the University Hospital of Ioannina, from 1 March 2020 to 31 May 2022. Venous thromboembolism was defined as a diagnosis of pulmonary embolism (PE) and/or vascular tree-in-bud in the lungs. The burden of disease, assessed by computed tomography of the lungs (CTBoD), was quantified as the percentage (%) of the affected lung parenchyma. The study outcomes were defined as death, intubation, and length of hospital stay (LoS). A chi-squared test and univariate logistic regression analyses were performed in IBM SPSS 28.0. RESULTS After propensity score matching, the final study cohort included 532 patients. VTE was found in 11.2% of the total population. In patients with VTE, we found that lymphocytopenia and a high neutrophil/lymphocyte ratio were associated with an increased risk of intubation and death, respectively. Similarly, CTBoD > 50% was associated with a higher risk of intubation and death in this group of patients. The triglyceride-glucose (TyG) index was also linked to worse outcomes. CONCLUSIONS Inflammatory indices were associated with VTE. Lymphocytopenia and an increased neutrophil-to-lymphocyte ratio negatively impacted the disease's prognosis and outcomes. Whether these indices unfavorably affect outcomes in COVID-19-associated VTE must be further evaluated.
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Affiliation(s)
- Angelos Liontos
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Dimitrios Biros
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Rafail Matzaras
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | | | - Nikolaos-Gavriel Kolios
- Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece; (N.-G.K.); (C.P.); (M.N.); (E.P.)
| | - Athina Zarachi
- Department of Otorhinolaryngology, Head and Neck Surgery, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 451100 Ioannina, Greece;
| | - Konstantinos Tatsis
- Department of Respiratory Medicine, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 451100 Ioannina, Greece;
| | - Christiana Pappa
- Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece; (N.-G.K.); (C.P.); (M.N.); (E.P.)
| | - Maria Nasiou
- Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece; (N.-G.K.); (C.P.); (M.N.); (E.P.)
| | - Eleni Pargana
- Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece; (N.-G.K.); (C.P.); (M.N.); (E.P.)
| | - Ilias Tsiakas
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Diamantina Lymperatou
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Sempastien Filippas-Ntekouan
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Lazaros Athanasiou
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Valentini Samanidou
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Revekka Konstantopoulou
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Ioannis Vagias
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Aikaterini Panteli
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Haralampos Milionis
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
| | - Eirini Christaki
- 1st Division of Internal Medicine & Infectious Diseases Unit, University General Hospital of Ioannina, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece; (A.L.); (D.B.); (R.M.); (I.T.); (D.L.); (S.F.-N.); (L.A.); (V.S.); (R.K.); (I.V.); (A.P.); (H.M.)
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Rauch-Kröhnert U, Puccini M, Placzek M, Beyer-Westendorf J, Jakobs K, Friebel J, Hein S, Seidel M, Pieske B, Massberg S, Witzenrath M, Zeiher A, Friede T, Anker SD, Landmesser U. Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial. Clin Res Cardiol 2023; 112:1620-1638. [PMID: 37407731 PMCID: PMC10584737 DOI: 10.1007/s00392-023-02240-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 05/30/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization. METHODS COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted D-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the D-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization. RESULTS The primary efficacy outcome D-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population D-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline D-dimer > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15-1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups. CONCLUSIONS Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by D-dimer > 2 ULN needs confirmation in further studies.
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Affiliation(s)
- Ursula Rauch-Kröhnert
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203, Berlin, Germany.
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
- Friede Springer Cardiovascular Prevention Center @ Charite Universitätsmedizin Berlin, Berlin, Germany.
| | - Marianna Puccini
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Marius Placzek
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
- Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
| | - Jan Beyer-Westendorf
- Department of Medicine I, Universitätsklinikum "Carl Gustav Carus" Dresden, Dresden, Germany
| | - Kai Jakobs
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Julian Friebel
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203, Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Selina Hein
- Katholisches Klinikum Koblenz-Montabaur, Koblenz, Germany
| | - Mirko Seidel
- BG Klinikum Unfallkrankenhaus Berlin, Berlin, Germany
| | - Burkert Pieske
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany
- German Heart Center Berlin, Berlin, Germany
- Department of Cardiology Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Steffen Massberg
- Department of Medicine I, LMU Klinikum, Ludwig-Maximilians-Universität München, Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich, Munich, Germany
| | - Martin Witzenrath
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany
- Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Zeiher
- Division of Cardiology, Department of Medicine III, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Rhine-Main, Frankfurt, Germany
| | - Tim Friede
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
- Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
| | - Stefan D Anker
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Campus Virchow Klinikum, Berlin, Germany
- Berlin Institute of Health Center for Regenerative Therapies (BCRT), Berlin, Germany
| | - Ulf Landmesser
- Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charite Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutsches Herzzentrum der Charité, Hindenburgdamm 30, 12203, Berlin, Germany.
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
- Friede Springer Cardiovascular Prevention Center @ Charite Universitätsmedizin Berlin, Berlin, Germany.
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.
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Greco S, Made' A, Mutoli M, Zhang L, Piella SN, Vausort M, Lumley AI, Beltrami AP, Srivastava PK, Milani V, Boveri S, Ranucci M, Renna LV, Firat H, Bruno A, Spinetti G, Emanueli C, Devaux Y, Martelli F. HCG18, LEF1AS1 and lncCEACAM21 as biomarkers of disease severity in the peripheral blood mononuclear cells of COVID-19 patients. J Transl Med 2023; 21:758. [PMID: 37884975 PMCID: PMC10605335 DOI: 10.1186/s12967-023-04497-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 09/01/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND Even after 3 years from SARS-CoV-2 identification, COVID-19 is still a persistent and dangerous global infectious disease. Significant improvements in our understanding of the disease pathophysiology have now been achieved. Nonetheless, reliable and accurate biomarkers for the early stratification of COVID-19 severity are still lacking. Long noncoding RNAs (LncRNAs) are ncRNAs longer than 200 nucleotides, regulating the transcription and translation of protein-coding genes and they can be found in the peripheral blood, thus holding a promising biomarker potential. Specifically, peripheral blood mononuclear cells (PBMCs) have emerged as a source of indirect biomarkers mirroring the conditions of tissues: they include monocytes, B and T lymphocytes, and natural killer T cells (NKT), being highly informative for immune-related events. METHODS We profiled by RNA-Sequencing a panel of 2906 lncRNAs to investigate their modulation in PBMCs of a pilot group of COVID-19 patients, followed by qPCR validation in 111 hospitalized COVID-19 patients. RESULTS The levels of four lncRNAs were found to be decreased in association with COVID-19 mortality and disease severity: HLA Complex Group 18-242 and -244 (HCG18-242 and HCG18-244), Lymphoid Enhancer Binding Factor 1-antisense 1 (LEF1-AS1) and lncCEACAM21 (i.e. ENST00000601116.5, a lncRNA in the CEACAM21 locus). Interestingly, these deregulations were confirmed in an independent patient group of hospitalized patients and by the re-analysis of publicly available single-cell transcriptome datasets. The identified lncRNAs were expressed in all of the PBMC cell types and inversely correlated with the neutrophil/lymphocyte ratio (NLR), an inflammatory marker. In vitro, the expression of LEF1-AS1 and lncCEACAM21 was decreased upon THP-1 monocytes exposure to a relevant stimulus, hypoxia. CONCLUSION The identified COVID-19-lncRNAs are proposed as potential innovative biomarkers of COVID-19 severity and mortality.
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Affiliation(s)
- Simona Greco
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy.
| | - Alisia Made'
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy
| | - Martina Mutoli
- IRCCS MultiMedica, Via Fantoli 16/15, 20138, Milan, Italy
| | - Lu Zhang
- Bioinformatics Platform, Data Integration and Analysis Unit, Luxembourg Institute of Health, 1445, Strassen, Luxembourg
| | - Santiago Nicolas Piella
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy
| | - Mélanie Vausort
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445, Strassen, Luxembourg
| | - Andrew I Lumley
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445, Strassen, Luxembourg
| | | | - Prashant Kumar Srivastava
- National Heart and Lung Institute, Imperial College London, Hammersmith Campus, London, W12 0NN, England, UK
| | - Valentina Milani
- Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS Policlinico San Donato, 20097, San Donato Milanese, Milan, Italy
| | - Sara Boveri
- Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS Policlinico San Donato, 20097, San Donato Milanese, Milan, Italy
| | - Marco Ranucci
- Department of Cardiovascular Anesthesia and ICU, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy
| | - Laura Valentina Renna
- Biobank BioCor, IRCCS-Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy
| | | | - Antonino Bruno
- IRCCS MultiMedica, Via Fantoli 16/15, 20138, Milan, Italy
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Via Monte Generoso 71, 21100, Varese, Italy
| | - Gaia Spinetti
- IRCCS MultiMedica, Via Fantoli 16/15, 20138, Milan, Italy
| | - Costanza Emanueli
- National Heart and Lung Institute, Imperial College London, Hammersmith Campus, London, W12 0NN, England, UK.
- National Heart & Lung Institute, Imperial College London, Guy Scadding Building, Cale Street, London, SW3 6LY, UK.
| | - Yvan Devaux
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1445, Strassen, Luxembourg.
| | - Fabio Martelli
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Milan, Italy.
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Walborn AT, Heath A, Neal MD, Zarychanski R, Kornblith LZ, Hunt BJ, Castellucci LA, Hochman JS, Lawler PR, Paul JD. Effects of inflammation on thrombosis and outcomes in COVID-19: secondary analysis of the ATTACC/ACTIV-4a trial. Res Pract Thromb Haemost 2023; 7:102203. [PMID: 37854455 PMCID: PMC10579532 DOI: 10.1016/j.rpth.2023.102203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 07/10/2023] [Accepted: 07/12/2023] [Indexed: 10/20/2023] Open
Abstract
Background Patients hospitalized for COVID-19 are at high risk of thrombotic complications and organ failure, and often exhibit severe inflammation, which may contribute to hypercoagulability. Objectives To determine whether patients hospitalized for COVID-19 experience differing frequencies of thrombotic and organ failure complications and derive variable benefits from therapeutic-dose heparin dependent on the extent of systemic inflammation and whether observed benefit from therapeutic-dose anticoagulation varies depending on the degree of systemic inflammation. Methods We analyzed data from 1346 patients hospitalized for COVID-19 enrolled in the ATTACC and ACTIV-4a platforms who were randomized to therapeutic-dose heparin or usual care for whom levels of C-reactive protein (CRP) were reported at baseline. Results Increased CRP was associated with worse patient outcomes, including a >98% posterior probability of increased organ support requirement, hospital length of stay, risk of 28-day mortality, and incidence of major thrombotic events or death (patients with CRP 40-100 mg/L or ≥100 mg/L compared to patients with CRP <40 mg/L). Patients with CRP 40 to 100 mg/L experienced the greatest degree of benefit from treatment with therapeutic doses of unfractionated or low molecular weight heparin compared with usual-care prophylactic doses. This was most significant for an increase in organ support-free days (odds ratio: 1.63; 95% confidence interval, 1.09-2.40; 97.9% posterior probability of beneficial effect), with trends toward benefit for other evaluated outcomes. Conclusion Moderately ill patients hospitalized for COVID-19 with CRP between 40 mg/L and 100 mg/L derived the greatest benefit from treatment with therapeutic-dose heparin.
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Affiliation(s)
- Amanda T. Walborn
- Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, Illinois, USA
| | - Anna Heath
- The Hospital for Sick Children, Toronto, Ontario, Canada
- Division of the Biostatistics, The University of Toronto, Toronto, Ontario, Canada
- Department of Statistical Science, University College London, London, UK
| | - Matthew D. Neal
- Pittsburgh Trauma and Transfusion Medicine Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ryan Zarychanski
- Department of Internal Medicine, Sections of Hematology/Medical Oncology and Critical Care, Max Rad College of Medicine, University of Manitoba, Winnipeg, Manitoba
| | - Lucy Z. Kornblith
- University of California, San Francisco, San Francisco, California, USA
| | - Beverley J. Hunt
- Thrombosis & Haemophilia Centre, Kings Healthcare Partners, London, UK
| | - Lana A. Castellucci
- Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Judith S. Hochman
- Department of Medicine, Section of Cardiology, NYU Langone Health, New York, New York, USA
| | - Patrick R. Lawler
- Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada
- Division of Cardiology and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jonathan D. Paul
- Department of Medicine, Section of Cardiology, University of Chicago Medical Center, Chicago, Illinois, USA
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Thaler S, Stöhr D, Kammerer T, Nitschke T, Hoechter DJ, Brandes F, Müller M, Groene P, Schäfer ST. Predictive value of coagulation variables and glycocalyx shedding in hospitalized COVID-19 patients - a prospective observational study. Acta Clin Belg 2023; 78:392-400. [PMID: 37092324 DOI: 10.1080/17843286.2023.2204593] [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: 12/15/2022] [Accepted: 04/15/2023] [Indexed: 04/25/2023]
Abstract
OBJECTIVES Covid-19 disease causes an immense burden on the healthcare system. It has not yet been finally clarified which patients will suffer from a severe course and which will not. Coagulation disorders can be detected in many of these patients. The aim of the present study was therefore to identify variables of the coagulation system including standard and viscoelastometric tests as well as components of glycocalyx damage that predict admission to the intensive care unit. METHODS Adult patients were included within 24 h of admission. Blood samples were analyzed at hospital admission and at ICU admission if applicable. We analyzed group differences and furthermore performed receiver operator characteristics (ROC). RESULTS This study included 60 adult COVID-19 patients. During their hospital stay, 14 patients required ICU treatment. Comparing ICU and non-ICU patients at time of hospital admission, D-dimer (1450 µg/ml (675/2850) vs. 600 µg/ml (500/900); p = 0.0022; cut-off 1050 µg/ml, sensitivity 71%, specificity 89%) and IL-6 (47.6 pg/ml (24.9/85.4 l) vs. 16.1 pg/ml (5.5/34.4); p = 0.0003; cut-off 21.25 pg/ml, sensitivity 86%, specificity 65%) as well as c-reactive protein (92 mg/dl (66.8/131.5) vs. 43.5 mg/dl (26.8/83.3); p = 0.0029; cutoff 54.5 mg/dl, sensitivity 86%, specificity 65%) were higher in patients who required ICU admission. Thromboelastometric variables and markers of glycocalyx damage (heparan sulfate, hyaluronic acid, syndecan-1) at the time of hospital admission did not differ between groups. CONCLUSION General inflammatory variables continue to be the most robust predictors of a severe course of a COVID-19 infection. Viscoelastometric variables and markers of glycocalyx damage are significantly increased upon admission to the ICU without being predictors of ICU admission.
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Affiliation(s)
- Sarah Thaler
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | - Dana Stöhr
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | - Tobias Kammerer
- Department of Anaesthesiology, University Hospital, Munich, Germany
- Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany
| | - Tobias Nitschke
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | | | - Florian Brandes
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | - Martin Müller
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | - Philipp Groene
- Department of Anaesthesiology, University Hospital, Munich, Germany
| | - Simon T Schäfer
- Department of Anaesthesiology, University Hospital, Munich, Germany
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Alijotas-Reig J, Anunciación-Llunell A, Morales-Pérez S, Trapé J, Esteve-Valverde E, Miro-Mur F. Thrombosis and Hyperinflammation in COVID-19 Acute Phase Are Related to Anti-Phosphatidylserine and Anti-Phosphatidylinositol Antibody Positivity. Biomedicines 2023; 11:2301. [PMID: 37626797 PMCID: PMC10452204 DOI: 10.3390/biomedicines11082301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/11/2023] [Accepted: 08/12/2023] [Indexed: 08/27/2023] Open
Abstract
Antiphospholipid antibodies (APLA) are strongly associated with thrombosis seen in patients with antiphospholipid syndrome. In COVID-19, thrombosis has been observed as one of the main comorbidities. In patients hospitalised for COVID-19, we want to check whether APLA positivity is associated with COVID-19-related thrombosis, inflammation, severity of disease, or long COVID-19. We enrolled 92 hospitalised patients with COVID-19 between March and April 2020 who were tested for 18 different APLAs (IgG and IgM) with a single line-immunoassay test. A total of 30 healthy blood donors were used to set the cut-off for each APLA positivity. Of the 92 COVID-19 inpatients, 30 (32.61%; 95% CI [23.41-43.29]) tested positive for APLA, of whom 10 (33.3%; 95% CI [17.94-52.86]) had more than one APLA positivity. Anti-phosphatidylserine IgM positivity was described in 5.4% of inpatients (n = 5) and was associated with the occurrence of COVID-19-related thrombosis (p = 0.046). Anti-cardiolipin IgM positivity was the most prevalent among the inpatients (n = 12, 13.0%) and was associated with a recorded thrombosis in their clinical history (p = 0.044); however, its positivity was not associated with the occurrence of thrombosis during their hospitalisation for COVID-19. Anti-phosphatidylinositol IgM positivity, with a prevalence of 5.4% (n = 5), was associated with higher levels of interleukin (IL)-6 (p = 0.007) and ferritin (p = 0.034). Neither of these APLA positivities was a risk factor for COVID-19 severity or a predictive marker for long COVID-19. In conclusion, almost a third of COVID-19 inpatients tested positive for at least one APLA. Anti-phosphatidylserine positivity in IgM class was associated with thrombosis, and anti-phosphatidylinositol positivity in IgM class was associated with inflammation, as noticed by elevated levels of IL-6. Thus, testing for non-criteria APLA to assess the risk of clinical complications in hospitalised COVID-19 patients might be beneficial. However, they were not related to disease severity or long COVID-19.
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Affiliation(s)
- Jaume Alijotas-Reig
- Systemic Autoimmune Diseases Research Unit, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Catalonia, Spain;
- Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron (HUVH), 08035 Barcelona, Catalonia, Spain
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain
| | - Ariadna Anunciación-Llunell
- Systemic Autoimmune Diseases Research Unit, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Catalonia, Spain;
| | - Stephanie Morales-Pérez
- Systemic Autoimmune Disease Unit, Internal Medicine Department, Althaia Healthcare University Network of Manresa, 08243 Manresa, Catalonia, Spain (J.T.)
| | - Jaume Trapé
- Systemic Autoimmune Disease Unit, Internal Medicine Department, Althaia Healthcare University Network of Manresa, 08243 Manresa, Catalonia, Spain (J.T.)
| | - Enrique Esteve-Valverde
- Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitari Parc Taulí, 08208 Sabadell, Catalonia, Spain
| | - Francesc Miro-Mur
- Systemic Autoimmune Diseases Research Unit, Vall d’Hebron Institut de Recerca (VHIR), 08035 Barcelona, Catalonia, Spain;
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Szilveszter M, Pál S, Simon-Szabó Z, Akácsos-Szász OZ, Moldován M, Réger B, Dénes L, Faust Z, Tilinca MC, Nemes-Nagy E. The Management of COVID-19-Related Coagulopathy: A Focus on the Challenges of Metabolic and Vascular Diseases. Int J Mol Sci 2023; 24:12782. [PMID: 37628963 PMCID: PMC10454092 DOI: 10.3390/ijms241612782] [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: 07/01/2023] [Revised: 08/07/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.
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Affiliation(s)
- Mónika Szilveszter
- Clinic of Plastic Surgery, Mureș County Emergency Hospital, 540136 Târgu-Mureș, Romania;
| | - Sándor Pál
- Department of Transfusion Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Zsuzsánna Simon-Szabó
- Department of Pathophysiology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania
| | - Orsolya-Zsuzsa Akácsos-Szász
- Doctoral School, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Mihály Moldován
- Klinik für Suchttherapie, ZtP Winnenden-Haus der Gesundheit, 73525 Schwäbisch Gümund, Germany;
| | - Barbara Réger
- Department of Laboratory Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Lóránd Dénes
- Department of Anatomy and Embryology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Zsuzsanna Faust
- Department of Transfusion Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary;
| | - Mariana Cornelia Tilinca
- Department of Internal Medicine I, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
| | - Enikő Nemes-Nagy
- Department of Chemistry and Medical Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu-Mureș, 540142 Târgu-Mureș, Romania;
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Shahbazi S, Vahdat Shariatpanahi Z, Shahbazi E. Bosentan for high-risk outpatients with COVID-19 infection: a randomized, double blind, placebo-controlled trial. EClinicalMedicine 2023; 62:102117. [PMID: 37554128 PMCID: PMC10404861 DOI: 10.1016/j.eclinm.2023.102117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 07/06/2023] [Accepted: 07/07/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND The endothelium is supposedly activated and damaged in COVID-19 because of endothelin-1 over-secretion. This study evaluates the effect of bosentan as an endothelin receptor blocker on the progression of disease in high-risk outpatients with COVID-19 infection. METHODS From 15 December 2021 to 15 May 2022, high-risk outpatients were randomly assigned to receive bosentan, 62.5 mg or placebo twice daily from enrollment for 30 days. Both groups received standard medical treatment too. On day 30 of the trial, the patients underwent complete doppler ultrasound of the lower extremities to detect asymptomatic thromboembolic events. The primary outcome in this study was hospitalization or death from any cause within the first 15 days. Secondary outcomes included thromboembolic events, hospital-free days and death from any cause within 30 days after randomization (IRCT.ir, IRCT20211203053263N1). FINDINGS Basal characteristics of the two groups were similar. Primary outcomes occurred in 3 (2.3%) of the 129 patients in the bosentan group versus 15 (11.5%) of the 130 patients in the placebo group [risk difference: -9.2% (95% CI: -15.3 to -3.1), P = 0.006]. Median hospital-free days was significantly higher in the bosentan group (P = 0.004). A total of three deaths occurred and all were in the control group. Bosentan was associated with a nonsignificant reduction in mortality compared with placebo (P = 0.24). Thromboembolic events occurred in one (1%) of 97 patients in the bosentan group versus nine (8.7%) of 104 patients in the placebo group within 30 days after randomization [risk difference: -8.3% (95% CI: -14.4 to -2.2), P = 0.008]. INTERPRETATION Early administration of bosentan may prevent disease progression and thromboembolic events in high-risk outpatients with COVID-19. FUNDING This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Affiliation(s)
- Shaahin Shahbazi
- Department of Internal Medicine, Faculty of Medicine, Ilam University of Medical Sciences, Iran
| | - Zahra Vahdat Shariatpanahi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Iran
| | - Erfan Shahbazi
- School of Medicine, Tehran University of Medical Sciences, Iran
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Ena J, Valls V. Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials. Clin Exp Med 2023; 23:1189-1196. [PMID: 36048371 PMCID: PMC9435420 DOI: 10.1007/s10238-022-00876-3] [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: 07/22/2022] [Accepted: 08/10/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. METHODS We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. RESULTS Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67-1.07; P = 0.16; I2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73-1.08; P = 0.24; I2: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28-0.62; P = 0.0001; I2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. CONCLUSION Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.
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Affiliation(s)
- Javier Ena
- Servicio de Medicina Interna, Department of Internal Medicine, Hospital Marina Baixa, Av Jaime Botella Mayor, 7, 03570, Villajoyosa, Alicante, Spain.
| | - Victoria Valls
- Department of Public Health, University Miguel Hernandez, Alicante, Spain
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Pagliarin LG, de Oliveira LM, dos Anjos VNF, de Souza CDBT, Peiter GC, Façanha Wendel C, Dillmann Groto A, Freire de Melo F, Teixeira KN. In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment. World J Biol Chem 2023; 14:72-83. [PMID: 37547340 PMCID: PMC10401403 DOI: 10.4331/wjbc.v14.i4.72] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 04/30/2023] [Accepted: 07/03/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has demonstrated several clinical manifestations which include not only respiratory system issues but also liver, kidney, and other organ injuries. One of these abnormalities is coagulopathies, including thrombosis and disseminated intravascular coagulation. Because of this, the administration of low molecular weight heparin is required for patients that need to be hospitalized. In addition, Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome, Ebola, Acute Respiratory Syndrome, and other diseases, showing satisfactory results on recovery. Besides, there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19. AIM To investigate in silico the interaction between Remdesivir and clotting factors, pursuing a possibility of using it as medicine. METHODS In this in silico study, the 3D structures of angiotensin-converting enzyme 2 (ACE2), Factor I (fibrinogen), Factor II (prothrombin), Factor III (thromboplastin), Factor V (proaccelerin), Factor VII (proconvertin), Factor VIII (antihemophilic factor A), Factor IX (antihemophilic factor B), Factor X (Stuart-Prower factor), and Factor XI (precursor of thromboplastin (these structures are technically called receptors) were selected from the Protein Data Bank. The structures of the antivirals Remdesivir and Osetalmivir (these structures are called ligands) were selected from the PubChem database, while the structure of Atazanavir was selected from the ZINC database. The software AutoDock Tools (ADT) was used to prepare the receptors for molecular docking. Ions, peptides, water molecules, and other ones were removed from each ligand, and then, hydrogen atoms were added to the structures. The grid box was delimited and calculated using the same software ADT. A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors, and still the software Marvin sketch® (ChemAxon®) was used to forecast the protonation state. To perform molecular docking, ADT and Vina software was connected. Using PyMol® software and Discovery studio® software from BIOVIA, it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands. Ligand tortions, atoms that participated in the interactions, and the type, strength, and duration of the interactions were also analyzed using those software. RESULTS Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of -8.8 kcal/moL, forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2. Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor. Similar to that, Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor. While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor, and Factor VII connected with the drug by four hydrogen bonds, which involved three atoms of the drug and three residues of amino acids of the factor. The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor, plus one electrostatic bond and three hydrophobic interactions. Factor X and Remdesivir had an affinity energy of -9.6 kcal/moL, and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor. The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms. CONCLUSION Because of the in silico significant affinity, Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.
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Affiliation(s)
| | | | | | | | - Gabrielle Caroline Peiter
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
| | | | | | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde - Campus Anísio Teixeira, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Kádima Nayara Teixeira
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
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Yaluri N, Stančáková Yaluri A, Žeňuch P, Žeňuchová Z, Tóth Š, Kalanin P. Cardiac Biomarkers and Their Role in Identifying Increased Risk of Cardiovascular Complications in COVID-19 Patients. Diagnostics (Basel) 2023; 13:2508. [PMID: 37568870 PMCID: PMC10417576 DOI: 10.3390/diagnostics13152508] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/03/2023] [Accepted: 07/17/2023] [Indexed: 08/13/2023] Open
Abstract
Cardiovascular disease (CVD) is a global health concern, causing significant morbidity and mortality. Both lifestyle and genetics influence the development of CVD. It is often diagnosed late, when the treatment options are limited. Early diagnosis of CVD with help of biomarkers is necessary to prevent adverse outcomes. SARS-CoV-2 infection can cause cardiovascular complications even in patients with no prior history of CVD. This review highlights cardiovascular biomarkers, including novel ones, and their applications as diagnostic and prognostic markers of cardiovascular complications related to SARS-CoV-2 infection. Patients with severe SARS-CoV-2 infection were shown to have elevated levels of cardiac biomarkers, namely N-terminal pro-brain natriuretic peptide (NT-pro-BNP), creatine kinase-myocardial band (CK-MB), and troponins, indicating acute myocardial damage. These biomarkers were also associated with higher mortality rates and therefore should be used throughout COVID-19 patient care to identify high-risk patients promptly to optimize their outcomes. Additionally, microRNAs (miRNAs) are also considered as potential biomarkers and predictors of cardiac and vascular damage in SARS-CoV-2 infection. Identifying molecular pathways contributing to cardiovascular manifestations in COVID-19 is essential for development of early biomarkers, identification of new therapeutic targets, and better prediction and management of cardiovascular outcomes.
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Affiliation(s)
- Nagendra Yaluri
- Center of Clinical and Preclinical Research, University Research Park Medipark, P. J. Šafárik University, 040 01 Košice, Slovakia
| | | | - Pavol Žeňuch
- Center of Clinical and Preclinical Research, University Research Park Medipark, P. J. Šafárik University, 040 01 Košice, Slovakia
| | - Zuzana Žeňuchová
- Center of Clinical and Preclinical Research, University Research Park Medipark, P. J. Šafárik University, 040 01 Košice, Slovakia
| | - Štefan Tóth
- Center of Clinical and Preclinical Research, University Research Park Medipark, P. J. Šafárik University, 040 01 Košice, Slovakia
| | - Peter Kalanin
- Center of Clinical and Preclinical Research, University Research Park Medipark, P. J. Šafárik University, 040 01 Košice, Slovakia
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Mancilla-Ceballos R, Milne KM, Guenette JA, Cortes-Telles A. Inflammation associated with lung function abnormalities in COVID-19 survivors. BMC Pulm Med 2023; 23:235. [PMID: 37391742 DOI: 10.1186/s12890-023-02521-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 06/16/2023] [Indexed: 07/02/2023] Open
Abstract
BACKGROUND Activation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors. METHODS Patients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge. RESULTS 100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome. CONCLUSION Overexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19.
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Affiliation(s)
- Roberto Mancilla-Ceballos
- Internal Medicine Department, Hospital Regional de Alta Especialidad de La Peninsula de Yucatan, Yucatan, Mexico
| | - Kathryn M Milne
- Department of Medicine, The University of British Columbia, Vancouver, Canada
- Centre for Heart Lung Innovation, Providence Research, The University of British Columbia and St. Paul's Hospital, Vancouver, Canada
| | - Jordan A Guenette
- Centre for Heart Lung Innovation, Providence Research, The University of British Columbia and St. Paul's Hospital, Vancouver, Canada
- Department of Physical Therapy, The University of British Columbia, Vancouver, Canada
| | - Arturo Cortes-Telles
- Respiratory Diseases Clinic, Hospital Regional de Alta Especialidad de La Peninsula de Yucatan, Yucatan, Mexico.
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Weiss LJ, Drayss M, Manukjan G, Zeitlhöfler M, Kleiss J, Weigel M, Herrmann J, Mott K, Beck S, Burkard P, Lâm TT, Althaus K, Bakchoul T, Frantz S, Meybohm P, Nieswandt B, Weismann D, Schulze H. Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as a therapeutic target in COVID-19. Blood Adv 2023; 7:2324-2338. [PMID: 36053793 PMCID: PMC9462922 DOI: 10.1182/bloodadvances.2022008666] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 12/02/2022] Open
Abstract
Thromboembolic events are frequent and life-threating complications of COVID-19 but are also observed in patients with sepsis. Disseminated thrombosis can occur despite anticoagulation, suggesting that platelets play a direct but incompletely understood role. Several studies demonstrated altered platelet function in COVID-19 with some controversial findings, while underlying disease-specific mechanisms remain ill defined. We performed a comprehensive cohort study with 111 patients, comprising 37 with COVID-19, 46 with sepsis, and 28 with infection, compared with control participants. Platelet phenotype and function were assessed under static and flow conditions, revealing unexpected disease-specific differences. From hospital admission onward, platelets in COVID-19 failed to activate the integrin glycoprotein IIb/IIa (GPIIb/IIIa) in response to multiple agonists. Dense granule release was markedly impaired due to virtually missing granules, also demonstrated by whole-mount electron microscopy. By contrast, α-granule marker CD62P exposure was only mildly affected, revealing a subpopulation of PAC-1-/CD62P+ platelets, independently confirmed by automated clustering. This uncoupling of α-granule release was not observed in patients with sepsis, despite a similar disease severity. We found overall unaltered thrombus formation in COVID-19 and sepsis samples under venous shear rates, which was dependent on the presence of tissue factor. Unexpectedly, under arterial shear rates, thrombus formation was virtually abrogated in sepsis, whereas we detected overall normal-sized and stable thrombi in blood from patients with COVID-19. These thrombi were susceptible to subthreshold levels of GPIIb/IIIa blockers, eptifibatide, or tirofiban that had only a minor effect in control participants' blood. We provide evidence that low-dose GPIIb/IIIa blockade could be a therapeutic approach in COVID-19.
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Affiliation(s)
- Lukas J. Weiss
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
- Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany
| | - Maria Drayss
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
- Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany
| | - Georgi Manukjan
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
| | | | - Judith Kleiss
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
| | - Mathis Weigel
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
| | - Johannes Herrmann
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Kristina Mott
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
| | - Sarah Beck
- Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
| | - Philipp Burkard
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
| | - Thiên-Trí Lâm
- Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany
| | - Karina Althaus
- Centre for Clinical Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Tamam Bakchoul
- Centre for Clinical Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Stefan Frantz
- Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany
| | - Patrick Meybohm
- Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Würzburg, Germany
| | - Bernhard Nieswandt
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
- Rudolf Virchow Center, University of Würzburg, Würzburg, Germany
| | - Dirk Weismann
- Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany
| | - Harald Schulze
- Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany
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Peschke P, Weinand F. [Bilateral retinal hemorrhage after acute respiratory distress syndrome (ARDS) with COVID-19 pneumonia]. DIE OPHTHALMOLOGIE 2023; 120:652-655. [PMID: 35925349 PMCID: PMC9253253 DOI: 10.1007/s00347-022-01676-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 11/05/2022]
Affiliation(s)
- P Peschke
- Klinik für Augenheilkunde, BundeswehrZentralkrankenhaus Koblenz, Rübenacher Str. 170, 56072, Koblenz, Deutschland.
| | - F Weinand
- Klinik für Augenheilkunde, BundeswehrZentralkrankenhaus Koblenz, Rübenacher Str. 170, 56072, Koblenz, Deutschland
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Bonfim LCMG, Guerini IS, Zambon MG, Pires GB, Silva ACF, Gobatto ALN, Lopes MA, Brosnahan SB. Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials. J Crit Care 2023; 77:154344. [PMID: 37244209 PMCID: PMC10211463 DOI: 10.1016/j.jcrc.2023.154344] [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: 01/01/2023] [Revised: 04/10/2023] [Accepted: 04/11/2023] [Indexed: 05/29/2023]
Abstract
PURPOSE The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19. MATERIALS AND METHODS We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered. RESULTS Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53). CONCLUSION This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.
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Affiliation(s)
- Luana C M G Bonfim
- Department of Medicine, University of South Santa Catarina, Florianópolis, SC, Brazil.
| | - Isadora S Guerini
- Department of Medicine, State University of Western Paraná, Francisco Beltrão, PR, Brazil
| | - Marjorie G Zambon
- Department of Medicine, Mackenzie Evangelical University Hospital, Curitiba, PR, Brazil
| | - Gabriela B Pires
- Department of Medicine, School of Medicine Souza Marques, Rio de Janeiro, RJ, Brazil
| | - Amanda C F Silva
- Department of Medicine, Federal University of Santa Catarina, Florianópolis, SC, Brazil
| | - André L N Gobatto
- Department of Critical Care, São Rafael Hospital, Salvador, Bahia, Brazil; Department of Critical Care, Hospital da Cidade, Salvador, Bahia, Brazil
| | - Marcela A Lopes
- Department of Critical Care, Hospital da Cidade, Salvador, Bahia, Brazil
| | - Shari B Brosnahan
- Department of Pulmonary and Critical Care, New York University School of Medicine, New York, NY, USA
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Puccini M, Jakobs K, Reinshagen L, Friebel J, Schencke PA, Ghanbari E, Landmesser U, Haghikia A, Kränkel N, Rauch U. Galectin-3 as a Marker for Increased Thrombogenicity in COVID-19. Int J Mol Sci 2023; 24:ijms24097683. [PMID: 37175392 PMCID: PMC10178107 DOI: 10.3390/ijms24097683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/14/2023] [Accepted: 04/17/2023] [Indexed: 05/15/2023] Open
Abstract
Galectin-3 is a beta-galactoside-binding lectin involved in inflammation and lung fibrosis and postulated to enhance thrombosis. In COVID-19, it is considered to be a prognostic marker of severity. The aim of this study was to evaluate whether galectin-3 is associated with thrombogenicity in COVID-19. Patients with moderate-to-severe COVID-19 (COVpos; n = 55) and patients with acute respiratory diseases, but without COVID-19 (COVneg; n = 35), were included in the study. We measured the amount of galectin-3, as well as other platelet and coagulation markers, and correlated galectin-3 levels with these markers of thrombogenicity and with the SOFA Score values. We found that galectin-3 levels, as well as von Willebrand Factor (vWF), antithrombin and tissue plasminogen activator levels, were higher in the COVpos than they were in the COVneg cohort. Galectin-3 correlated positively with vWF, antithrombin and D-dimer in the COVpos cohort, but not in the COVneg cohort. Moreover, galactin-3 correlated also with clinical disease severity, as measured by the SOFA Score. In patients with acute respiratory diseases, galectin-3 can be considered as a marker not only for disease severity, but also for increased hypercoagulability. Whether galectin-3 might be a useful therapeutic target in COVID-19 needs to be assessed in future studies.
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Affiliation(s)
- Marianna Puccini
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
| | - Kai Jakobs
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
| | - Leander Reinshagen
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
| | - Julian Friebel
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany
| | - Philipp-Alexander Schencke
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
| | - Emily Ghanbari
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
| | - Ulf Landmesser
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany
| | - Arash Haghikia
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
- Berlin Institute of Health at Charité-Universitätsmedizin Berlin, 10178 Berlin, Germany
| | - Nicolle Kränkel
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
| | - Ursula Rauch
- Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, 12203 Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10178 Berlin, Germany
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45
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Shute JK. Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease. Pharmaceuticals (Basel) 2023; 16:ph16040584. [PMID: 37111341 PMCID: PMC10141002 DOI: 10.3390/ph16040584] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/06/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Unfractionated heparin has multiple pharmacological activities beyond anticoagulation. These anti-inflammatory, anti-microbial, and mucoactive activities are shared in part by low molecular weight and non-anticoagulant heparin derivatives. Anti-inflammatory activities include inhibition of chemokine activity and cytokine synthesis, inhibitory effects on the mechanisms of adhesion and diapedesis involved in neutrophil recruitment, inhibition of heparanase activity, inhibition of the proteases of the coagulation and complement cascades, inhibition of neutrophil elastase activity, neutralisation of toxic basic histones, and inhibition of HMGB1 activity. This review considers the potential for heparin and its derivatives to treat inflammatory lung disease, including COVID-19, ALI, ARDS, cystic fibrosis, asthma, and COPD via the inhaled route.
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Affiliation(s)
- Janis Kay Shute
- School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UK
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Gupta V, Acharya S, Keerti A. Common Coagulopathies Associated With COVID-19 Patients. Cureus 2023; 15:e38067. [PMID: 37234147 PMCID: PMC10208414 DOI: 10.7759/cureus.38067] [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: 01/16/2023] [Accepted: 04/24/2023] [Indexed: 05/27/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.
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Affiliation(s)
- Vinish Gupta
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND
| | - Sourya Acharya
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND
| | - Akshunna Keerti
- Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, IND
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Maghrabi KA, AlQahtany FS, AlOtair H, Maghrabi MK, AlSaleh K, Owaidah T. Prognostic markers in patients with COVID-19 requiring intensive critical support. J Taibah Univ Med Sci 2023; 18:1089-1098. [PMID: 36969317 PMCID: PMC9998242 DOI: 10.1016/j.jtumed.2023.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 02/05/2023] [Accepted: 02/27/2023] [Indexed: 03/12/2023] Open
Abstract
Objectives Several hematological and immunological markers, particularly neutrophil count, predict the severity of COVID-19. This study aimed at assessing hematological and coagulation parameters at different time points, to predict the complications or outcomes of patients with COVID-19 admitted to the intensive care unit (ICU). Methods We conducted a prospective observational multicenter study in ICU departments. A total of 118 patients with COVID-19 admitted to the ICU were included. Clinical data and blood samples from routine hematology and coagulation tests were collected at admission, and on days 3, 7, and 14. The main outcome measures were high-flow-O2 requirement, thrombosis, and 30-day mortality. Results The mean length of ICU stay for our cohort was 15.70 ± 19 days, and the median was 9 days. The length of stay was significantly prolonged in recovered patients (28.20 ± 29.90 days; chi-square P = 0.0022) and patients with thrombosis (34.40 ± 39.60 days; P = 0.024). A total of 113 (95.70%) patients received prophylactic anticoagulation after admission with different regimens; thrombosis was observed in four (3.90%) patients (P = 0.430), but none died. The venous thromboembolism score increased from a mean of 5.10 ± 2 on day 0 to 6.40 ± 2.80 on day 14 (P = 0.0002). The disseminated intravascular coagulation (DIC) score significantly correlated with thrombosis (P = 0.031). A total of 41.20% of patients in the ICU had a DIC score ≥4, and 11.40% had a score <4. Mortality was negatively associated with patients on high-flow O2, 9 patients (10.80%) (P = 0.040), and positively associated with patients receiving ventilation, 16 patients (27.50%) (P < 0.001). An increase in white blood cell count (subdistribution hazard ratio (SHR): 0.91; 95% CI: 0.80–1) and neutrophil count (SHR: 1; 95% CI: 1.01–1.05) was associated with greater disease severity and D-dimer level (SHR: 1.60; 95% CI: 1.10–2.5). Conclusion The venous thromboembolism score was significantly higher for patients who died than those who recovered. Furthermore, mechanical ventilation was associated with high mortality, whereas the risk of thrombosis and ICU admission correlated with high D-dimer values and DIC scores. Therefore, D-dimer levels and DIC scores are prognostic markers that may predict disease severity in patients with COVID-19.
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Affiliation(s)
- Khalid A. Maghrabi
- Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA
| | - Fatmah S. AlQahtany
- Department of Pathology, Hematopathology Unit, College of Medicine, King Saud University, King Saud University Medical City, Riyadh, KSA
| | - Hadeel AlOtair
- Department of Medicine, King Saud University, King Saud University Medical City, Riyadh, KSA
| | - Mohannad K. Maghrabi
- Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA
| | - Khalid AlSaleh
- Department of Medicine, College of Medicine, King Saud University, Riyadh, KSA
| | - Tarek Owaidah
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, KSA,Alfaisal University, Riyadh, KSA,Corresponding address: Haematology and Transfusion Medicine, King Faisal Specialist Hospital, Alfaisal University, Centre of Excellence in Thrombosis and Hemostasis, P.O. Box 3354, Riyadh 11211, KSA
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Filip C, Covali R, Socolov D, Pavaleanu I, Carauleanu A, Scripcariu IS, Vasilache IA, Akad M, Boiculese VL, Dimitriu C, Butureanu T, Melinte A, Filip C, Popa RF, Socolov R. COVID-19 in Pregnant Patients at Term: Evolution of Coagulation Factors in Mild Forms throughout the Pandemic: Conventional Analysis and Logistic Regression. MAEDICA 2023; 18:67-73. [PMID: 37266477 PMCID: PMC10231169 DOI: 10.26574/maedica.2023.18.1.67] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Aim: The evolution of coagulation factors in pregnant patients infected with SARS-CoV-2 during the pandemic is still debated. However, few studies have been carried out to evaluate the silent alterations of blood values in mild forms of the disease. Methods:A total of 153 pregnant patients with an asymptomatic form of COVID-19 and 306 healthy pregnant patients, who were admitted for delivery in our hospital between April 1, 2020 and March 1, 2022, were studied. The blood values harvested closest to the time of delivery were considered. Results:There was a significant variability in values of fibrinogen, prothrombin time, though these were still within normal limits. Conclusions:Pregnant patients with mild forms of COVID-19 displayed some blood alterations, even if they were asymptomatic for COVID-19.
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Affiliation(s)
- Catalina Filip
- Department of Vascular Surgery, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Roxana Covali
- Department of Radiology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Elena Doamna" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Demetra Socolov
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Cuza Voda" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Ioana Pavaleanu
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Elena Doamna" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Alexandru Carauleanu
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Cuza Voda" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Ioana Sadiye Scripcariu
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Cuza Voda" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Ingrid Andrada Vasilache
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Cuza Voda" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Mona Akad
- Doctoral student, Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Vasile Lucian Boiculese
- Department of Statistics, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Cristina Dimitriu
- Department of Biochemistry, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Tudor Butureanu
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Elena Doamna" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
| | - Alina Melinte
- Department of Obstetrics and Gynecology, Hereditas Hospital, 727325 Ipotesti, Romania
| | - Cristiana Filip
- Department of Biochemistry, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Radu Florin Popa
- Department of Vascular Surgery, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Razvan Socolov
- Department of Obstetrics and Gynecology, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, "Elena Doamna" Obstetrics and Gynecology University Hospital, 700115 Iasi, Romania
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Zhuang Z, Chen Q, Zhong X, Chen H, Yu R, Tang Y. Ginsenoside Rg3, a promising agent for NSCLC patients in the pandemic: a large-scale data mining and systemic biological analysis. J Ginseng Res 2023; 47:291-301. [PMID: 36249948 PMCID: PMC9553969 DOI: 10.1016/j.jgr.2022.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 09/12/2022] [Accepted: 09/27/2022] [Indexed: 11/07/2022] Open
Abstract
Introduction Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.
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Affiliation(s)
- Zhenjie Zhuang
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qianying Chen
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoying Zhong
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huiqi Chen
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Runjia Yu
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ying Tang
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China,Corresponding author. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, No.12, Ji Chang Road, Baiyun District, Guangzhou, 510405, China
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Oleksiuk-Bójko M, Lisowska A. Venous thromboembolism: Why is it still a significant health problem? Adv Med Sci 2023; 68:10-20. [PMID: 36368288 DOI: 10.1016/j.advms.2022.10.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 08/08/2022] [Accepted: 10/27/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Venous thromboembolism (VTE) remains the third leading cause of acute cardiovascular syndrome following myocardial infarction and ischemic stroke. The global burden of disease worldwide is high and shows a steady upward trend in recent years with an incidence of 1-2 per 1000 adults per year. The overarching goal of the initial management of VTE is to prevent early and late adverse outcomes. Rapid evaluation and therapeutic intervention is vital to improving prognosis. METHODS We searched PubMed, Science Direct and Scopus databases for articles published in the last 10 years. Additionally, some earlier articles were analyzed. RESULTS For the purposes of this review, we discussed how understanding the epidemiology of VTE and the current knowledge of early and late complications of this disease have shaped the current approach to VTE prevention. We also analyzed the current knowledge and the most up-to-date information about VTE in COVID-19 infection. Contemporary perspective presented in this article on mortality in VTE, the incidence of recurrences, the risk of major bleeding during therapy and the chronic complications indicate why this is a major challenge for today's medicine and a current target for further research. CONCLUSIONS Understanding the interaction between environmental and genetic factors appears to be crucial in the diagnostic process. It can provide insight into the pathophysiology of VTE, potentially identifying options for targeted prevention and treatment. However, due to differences in clinical presentation, diagnosing pulmonary embolism may not be an easy task which perfectly illustrates the scale and complexity of the disease.
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Affiliation(s)
- Monika Oleksiuk-Bójko
- Department of Cardiology, University Clinical Hospital in Bialystok, Bialystok, Poland
| | - Anna Lisowska
- Department of Cardiology, University Clinical Hospital in Bialystok, Bialystok, Poland.
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