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Monsalve DM, Acosta-Ampudia Y, Acosta NG, Celis-Andrade M, Şahin A, Yilmaz AM, Shoenfeld Y, Ramírez-Santana C. NETosis: A key player in autoimmunity, COVID-19, and long COVID. J Transl Autoimmun 2025; 10:100280. [PMID: 40071133 PMCID: PMC11894324 DOI: 10.1016/j.jtauto.2025.100280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 02/20/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.
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Affiliation(s)
- Diana M. Monsalve
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Yeny Acosta-Ampudia
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Nicolás Guerrero Acosta
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Mariana Celis-Andrade
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Ali Şahin
- Selcuk University, Faculty of Medicine, Konya, Turkiye
| | - Ahsen Morva Yilmaz
- TUBITAK Marmara Research Center (TUBITAK-MAM), Life Sciences, Medical Biotechnology Unit, Kocaeli, Turkiye
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Reichman University, Herzelia, Israel
| | - Carolina Ramírez-Santana
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
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Vasković I, Marković M, Udovičić I, Arsenović L, Stojić M, Ignjatović A, Jovanović D, Nešković V. Effectiveness of different anticoagulation regimens in critically ill patients - experience from COVID 19 patients. Blood Coagul Fibrinolysis 2025; 36:82-89. [PMID: 40053316 DOI: 10.1097/mbc.0000000000001354] [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: 12/16/2024] [Accepted: 02/23/2025] [Indexed: 04/05/2025]
Abstract
This study compared the efficacy of therapeutic anticoagulation guided by anti-Xa levels vs. a D-dimer-based protocol in ICU patients with COVID-19. Given the heightened risk of thrombosis despite anticoagulation therapy in some cases, we hypothesised that anti-Xa measurement improves anticoagulation effectiveness and clinical outcomes in this population. We retrospectively analysed data from ICU patients at COVID Hospital Karaburma between April 2020 and December 2021. The primary outcome was the incidence of failed noninvasive ventilation necessitating intubation. Secondary endpoints included mortality rates, thromboembolic and bleeding complications, and anticoagulation effectiveness assessed by antifactor Xa activity. The analysis included 395 patients - 137 in the anti-Xa group and 258 in the D-dimer group. The D-dimer group showed a higher rate of failed noninvasive ventilation requiring intubation (65.7% vs. 50%, P = 0.009). The overall mortality was 48.3%, significantly higher in the D-dimer group (52.7%) compared to the anti-Xa group (40.1%, P = 0.02). Thromboembolic complications were lower in the anti-Xa group (2.9%) than in the D-dimer group (9.7%, P = 0.014), with no significant difference in bleeding. Following the first LMWH administration, 70.8% of patients had anti-Xa levels below the therapeutic and 11.7% below the prophylactic range. Anti-Xa-guided anticoagulation improves survival and reduces thromboembolic complications compared to D-dimer-based treatment without increasing bleeding risk. This study highlights the potential of the anti-Xa assay in managing anticoagulation in critically ill COVID-19 patients. Our findings provide a foundation for future research on using anti-Xa measurements as a guiding tool to optimise anticoagulation therapy in other critically ill populations.
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Affiliation(s)
- Igor Vasković
- Clinic for Anesthesiology and Intensive Care, Military Medical Academy
| | - Marija Marković
- Clinic for Anesthesiology and Intensive Care, Military Medical Academy
| | - Ivo Udovičić
- Clinic for Anesthesiology and Intensive Care, Military Medical Academy
| | | | - Mihailo Stojić
- Clinic for Anesthesiology and Intensive Care, Military Medical Academy
| | | | - Dragana Jovanović
- Clinic for Anesthesiology and Intensive Care, Military Medical Academy
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Manolis TA, Manolis AA, Manolis AS. Emotional Stress in Cardiac and Vascular Diseases. Curr Vasc Pharmacol 2025; 23:172-195. [PMID: 39754763 DOI: 10.2174/0115701611328094241104062903] [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: 06/04/2024] [Revised: 08/13/2024] [Accepted: 09/02/2024] [Indexed: 01/06/2025]
Abstract
INTRODUCTION/OBJECTIVE Emotional, mental, or psychological distress, defined as increased symptoms of depression, anxiety, and/or stress, is common in patients with chronic diseases, such as cardiovascular (CV) disease (CVD). METHODS Literature was reviewed regarding data from studies and meta-analyses examining the impact of emotional stress on the occurrence and outcome of several CVDs (coronary disease, heart failure, hypertension, arrhythmias, stroke). These influences' pathophysiology and clinical spectrum are detailed, tabulated, and pictorially illustrated. RESULTS This type of stress is a newly recognized risk and prognosticator for CVD including coronary artery disease, heart failure, hypertension, cardiac arrhythmias, and stroke, independently of conventional risk factors. It can impact CV outcomes, and also affect health care utilization, with more patient visits to health care facilities. The biological systems activated by mental stress comprise the sympathetic nervous system (SNS), the renin-angiotensin system (RAS), and the hypothalamic- pituitary-adrenal (HPA) axis, while several other biological processes are disrupted, such as endothelial function, inflammatory responses, oxidative stress, mitochondrial function and the function of the amygdala which is the central nervous system processing center of emotions and emotional reactions. CONCLUSION Emotional stress that aggravates symptoms of depression, anxiety, and/or perceived mental stress is common in patients with chronic diseases, such as CVD. It is a newly recognized risk and prognosticator for several CVDs. It can influence CV outcomes, and also affect health care utilization. The biological systems activated by mental stress comprise the SNS, the RAS, and the HPA axis, while several other biological processes are disrupted.
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Affiliation(s)
- Theodora A Manolis
- Department of Psychiatry, Aiginiteio University Hospital, Athens, Greece
| | - Antonis A Manolis
- Department of Int. Medicine, Elpis General Hospital of Athens, Athens, Greece
| | - Antonis S Manolis
- Department of Cardiology, Ippokrateio University Hospital, Athens, Greece
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Manolis AA, Manolis TA, Manolis AS. Early-onset or Premature Coronary Artery Disease. Curr Med Chem 2025; 32:1040-1064. [PMID: 38840391 DOI: 10.2174/0109298673303891240528114755] [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: 02/15/2024] [Revised: 03/27/2024] [Accepted: 04/05/2024] [Indexed: 06/07/2024]
Abstract
The aim of this review was to examine the literature regarding younger individuals without classical risk factors for atherosclerosis who develop coronary artery disease (CAD) prematurely at an early age. An extensive literature review was undertaken in Pubmed, Scopus, and Google Scholar regarding early-onset or premature atherosclerosis, CAD, its diagnosis, management, and prophylaxis. There are individuals of both genders, particularly in the younger age group of 20-40 years of age, who lack the traditional/ classical risk factors and still develop CAD and other manifestations of atherosclerosis. Even the 10-year age gap in manifesting CAD that is noted between women and men ascribable to a cardioprotective effect of sex hormones may not be noted under these circumstances. This indicates that the risk profile differs in young patients with nonclassical atherosclerotic risk factors, and factors such as genetics, inflammation, thrombosis, psychosocial, environmental, and other parameters play an important role in atherosclerosis and other mechanisms that lead to CAD in younger individuals. These patients are at risk of major adverse cardiac events, which determine their prognosis. Unfortunately, current major guidelines do not acknowledge that many patients who manifest premature CAD are at high risk, and as a consequence, many of these patients may not be receiving guideline-directed hypolipidemic and other therapies before they present with symptoms of CAD. Caretakers need to be more vigilant in offering efficacious screening and strategies of prevention for early-onset or premature CAD to younger individuals.
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Affiliation(s)
- Antonis A Manolis
- First Department of Cardiology, Evagelismos General Hospital of Athens, Athens, Greece
| | - Theodora A Manolis
- Department of Psychiatry, Aiginiteio University Hospital, Athens, Greece
| | - Antonis S Manolis
- First Department of Cardiology, Athens University School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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Zhu W, Xu Z, Zhou D, Xu J, He Y, Li ZA. Bioengineering strategies targeting angiogenesis: Innovative solutions for osteonecrosis of the femoral head. J Tissue Eng 2025; 16:20417314241310541. [PMID: 39866964 PMCID: PMC11760140 DOI: 10.1177/20417314241310541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 12/14/2024] [Indexed: 01/28/2025] Open
Abstract
Osteonecrosis of the femoral head (ONFH) is a prevalent orthopedic disorder characterized primarily by compromised blood supply. This vascular deficit results in cell apoptosis, trabecular bone loss, and structural collapse of the femoral head at late stage, significantly impairing joint function. While MRI is a highly effective tool for diagnosing ONFH in its early stages, challenges remain due to the limited availability and high cost of MRI, as well as the absence of routine MRI screening in asymptomatic patients. . In addition, current therapeutic strategies predominantly only relieve symptoms while disease-modifying ONFH drugs are still under investigation/development. Considering that blood supply of the femoral head plays a key role in the pathology of ONFH, angiogenic therapies have been put forward as promising treatment options. Emerging bioengineering interventions targeting angiogenesis hold promising potential for ONFH treatment. In this review, we introduce the advances in research into the pathology of ONFH and summarize novel bioengineering interventions targeting angiogenesis. This review sheds light upon new directions for future research into ONFH.
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Affiliation(s)
- Weihong Zhu
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhenmu Xu
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ding Zhou
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China
- Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yuchen He
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhong Alan Li
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
- Key Laboratory of Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
- Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China
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Ahmad SA, Mayasi Y, Kelly TL, White N, Suen J, Battaglini D, Bassi GL, Fraser JF, Premraj L, Arora RC, Bastos D, Whitman G, Griffee M, Fanning JP, Robba C, Cho SM, the COVID-19 Critical Care Consortium. Neurological Complications and Outcomes in Critically Ill Patients With COVID-19: Results From International Neurological Study Group From the COVID-19 Critical Care Consortium. Neurohospitalist 2024:19418744241292487. [PMID: 39544265 PMCID: PMC11559469 DOI: 10.1177/19418744241292487] [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] [Indexed: 11/17/2024] Open
Abstract
Background In this COVID-19 Critical Care Consortium (CCCC) sub-study, we qualified neurological complications associated with SARS-CoV2 infection. Methods The CCCC is an international, multicenter study. Eligible patients were COVID-19 patients admitted to intensive care units (ICU) across 23 centers between 1/7/2020 to 6/23/2022. Incidence of neurological complications was estimated as number of events per hospital days and per admission using Poisson regression. Associations between neurological complications and risk factors were assessed using multivariable Poisson regression. Results 713 patients were included. Median age = 56 years (interquartile range (IQR) = 45-65). Neurological complications reported in 61/480 patients (12.7%) with the majority being ischemic stroke (2.9%), intracranial hemorrhage (ICH) (2.8%), and seizures (2.6%). Multivariable analysis for neurological complications per admitted days showed comorbid neurological conditions (incidence rate ratio (IRR) = 6.35, 2.57-15.7) were an independent risk factor for ischemic stroke. Extracorporeal membrane oxygenation (IRR = 5.32, 1.52-18.6), low-middle income countries (LMIC) vs high income countries (HIC) (IRR = 4.70, 1.62-13.7), and age >55 (IRR = 3.66, 1.23-10.9) were independent risk factors for ICH. Co-morbid neurological conditions (IRR = 3.43, 1.11-10.6), LMIC vs HIC (IRR = 8.69, 2.15-35.2), July-December 2020 vs January-June 2020 (IRR = 0.17, 0.04-0.69) and age >55 (IRR = 4.05, 1.15-14.3) were independent risk factors for seizure. Conclusions Decision-making should incorporate salient risk factors to inform management of SARS-CoV2 infection and avoid neurological complications.
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Affiliation(s)
- Syed Ameen Ahmad
- Department of Neurosciences Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Yunis Mayasi
- Department of Neurosciences Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Thu-Lan Kelly
- School of Public Health & Social Work, Queensland University of Technology, Brisbane, QLD, Australia
| | - Nicole White
- School of Public Health & Social Work, Queensland University of Technology, Brisbane, QLD, Australia
| | - Jacky Suen
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine University of Queensland, Brisbane, QLD, Australia
| | - Denise Battaglini
- Anesthesia and Intensive Care, IRCCS Policlinico San Martino, Genoa, Italy
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine University of Queensland, Brisbane, QLD, Australia
- Queensland University of Technology, Brisbane, QLD, Australia
- Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - John F. Fraser
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine University of Queensland, Brisbane, QLD, Australia
- Queensland University of Technology, Brisbane, QLD, Australia
- Critical Care Medicine, UnitingCare Health, Brisbane, QLD, Australia
| | - Lavien Premraj
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Griffith University School of Medicine, Gold Coast, QLD, Australia
| | - Rakesh C. Arora
- Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH, USA
- Division of Cardiac Surgery, Department of Surgery, Case Western Reserve University, Cleveland, OH, USA
| | | | - Glenn Whitman
- Department of Neurosciences Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthew Griffee
- Department of Anesthesiology and Perioperative Medicine, University of Utah, Salt Lake City, UT, USA
| | - Jonathon P. Fanning
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine University of Queensland, Brisbane, QLD, Australia
- Critical Care Medicine, UnitingCare Health, Brisbane, QLD, Australia
| | - Chiara Robba
- Anesthesia and Intensive Care, IRCCS Policlinico San Martino, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Sung-Min Cho
- Department of Neurosciences Critical Care, Departments of Neurology, Neurosurgery, Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Fouda EAAM, Badr EA, Gawesh D, Mahmoud MA. The role of NOS3-rs1799983 and NOS3- rs2070744 SNP in occurrence of avascular necrosis as a post COVID-19 complication. BMC Med Genomics 2024; 17:217. [PMID: 39169347 PMCID: PMC11337830 DOI: 10.1186/s12920-024-01928-1] [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: 01/07/2024] [Accepted: 06/06/2024] [Indexed: 08/23/2024] Open
Abstract
Avascular necrosis (AVN) is a debilitating condition characterized by bone tissue death due to inadequate blood supply, leading to joint dysfunction and collapse. This study investigates the potential association between AVN and COVID-19, focusing on genetic factors such as NOS3 polymorphisms. A total of 180 individuals were included, comprising 120 COVID-19 patients and 60 healthy controls. Clinical, haematological, biochemical, and genetic parameters were assessed. Results revealed significant differences in respiratory and heart rates, haematological counts, and biochemical markers between AVN and control groups. Genetic analysis showed a higher prevalence of the TG genotype and G allele in NOS3 rs1799983 polymorphism among AVN patients. Additionally, NOS3 rs2070744 polymorphism correlated with various clinical parameters, including blood pressure, heart rate, and haematological indices. This study highlights the potential role of genetic factors in predisposing individuals to AVN following COVID-19 infection.
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Affiliation(s)
| | - Eman Ae Badr
- Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Doaa Gawesh
- Department of Chemistry, Biochemistry Division, Faculty of Science, Menoufia University, Menoufia, Egypt
| | - Mohammad A Mahmoud
- Department of Chemistry, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.
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Negrut N, Menegas G, Kampioti S, Bourelou M, Kopanyi F, Hassan FD, Asowed A, Taleouine FZ, Ferician A, Marian P. The Multisystem Impact of Long COVID: A Comprehensive Review. Diagnostics (Basel) 2024; 14:244. [PMID: 38337760 PMCID: PMC10855167 DOI: 10.3390/diagnostics14030244] [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: 01/02/2024] [Revised: 01/20/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: the recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.
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Affiliation(s)
- Nicoleta Negrut
- Department of Psycho-Neuroscience and Recovery, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Georgios Menegas
- Department of Orthopaedics, Achillopouleio General Hospital of Volos, Polymeri 134, 38222 Volos, Greece;
| | - Sofia Kampioti
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania (M.B.); (F.D.H.)
| | - Maria Bourelou
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania (M.B.); (F.D.H.)
| | - Francesca Kopanyi
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania (M.B.); (F.D.H.)
| | - Faiso Dahir Hassan
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania (M.B.); (F.D.H.)
| | - Anamaria Asowed
- Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania (M.B.); (F.D.H.)
| | - Fatima Zohra Taleouine
- University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK;
| | - Anca Ferician
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (A.F.)
| | - Paula Marian
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (A.F.)
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Mackiewicz-Milewska M, Cisowska-Adamiak M, Pyskir J, Świątkiewicz I. Venous Thromboembolism in Patients Hospitalized for COVID-19 in a Non-Intensive Care Unit. J Clin Med 2024; 13:528. [PMID: 38256663 PMCID: PMC10816041 DOI: 10.3390/jcm13020528] [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: 12/26/2023] [Revised: 01/13/2024] [Accepted: 01/15/2024] [Indexed: 01/24/2024] Open
Abstract
Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may contribute to venous thromboembolism (VTE) with adverse effects on the course of COVID-19. The purpose of this study was to investigate an incidence and risk factors for VTE in patients hospitalized for COVID-19 in a non-intensive care unit (non-ICU). Consecutive adult patients with COVID-19 hospitalized from November 2021 to March 2022 in the isolation non-ICU at our center were included in the study. Incidence of VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT), clinical characteristics, and D-dimer plasma levels during the hospitalization were retrospectively evaluated. Among the 181 patients (aged 68.8 ± 16.2 years, 44% females, 39% Delta SARS-CoV-2 variant, 61% Omicron SARS-CoV-2 variant), VTE occurred in 29 patients (VTE group, 16% of the entire cohort). Of them, PE and DVT were diagnosed in 15 (8.3% of the entire cohort) and 14 (7.7%) patients, respectively. No significant differences in clinical characteristics were observed between the VTE and non-VTE groups. On admission, median D-dimer was elevated in both groups, more for VTE group (1549 ng/mL in VTE vs. 1111 ng/mL in non-VTE, p = 0.09). Median maximum D-dimer was higher in the VTE than in the non-VTE group (5724 ng/mL vs. 2200 ng/mL, p < 0.005). In the univariate analysis, systemic arterial hypertension and the need for oxygen therapy were predictors of VTE during hospitalization for COVID-19 (odds ratio 2.59 and 2.43, respectively, p < 0.05). No significant associations were found between VTE risk and other analyzed factors; however, VTE was more likely to occur in patients with a history of VTE, neurological disorders, chronic pulmonary or kidney disease, atrial fibrillation, obesity, and Delta variant infection. Thromboprophylaxis (83.4% of the entire cohort) and anticoagulant treatment (16.6%) were not associated with a decreased VTE risk. The incidence of VTE in patients hospitalized in non-ICU for COVID-19 was high despite the common use of thromboprophylaxis or anticoagulant treatment. A diagnosis of arterial hypertension and the need for oxygen therapy were associated with an increased VTE risk. Continuous D-dimer monitoring is required for the early detection of VTE.
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Affiliation(s)
- Magdalena Mackiewicz-Milewska
- Department of Rehabilitation, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland;
| | - Małgorzata Cisowska-Adamiak
- Department of Rehabilitation, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland;
| | - Jerzy Pyskir
- Department of Biophysics, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland;
| | - Iwona Świątkiewicz
- Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA 92037, USA;
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Abel P, Bülow R, Stubbe B, Heine A, Ewert R. [Fatal course of pulmonary embolism after successful pulmonary endarterectomy: a rare case]. Pneumologie 2023; 77:1009-1012. [PMID: 37857318 DOI: 10.1055/a-2161-5962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2023]
Abstract
We report a case of a 43-year-old woman who suffered from recurrent pulmonary embolism leading to chronic thromboembolic pulmonary hypertension. Pulmonary endarterectomy was performed with good result. However, two years later, after a SARS-CoV2 infection and despite oral anticoagulation therapy, the patient presented with clinical symptoms of pulmonary embolism, which was confirmed by computed tomography as an extensive pulmonary embolism. Despite fibrinolysis therapy and the attempt of interventional thrombus aspiration, the patient died due to non-manageable embolism load.
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Affiliation(s)
- Peter Abel
- Internal Medicine B, University Medicine Greifswald, Greifswald, Deutschland
| | - Robin Bülow
- Radiology, University Medicine Greifswald, Greifswald, Deutschland
| | - Beate Stubbe
- Internal Medicine B, University Medicine Greifswald, Greifswald, Deutschland
| | - Alexander Heine
- Internal Medicine B, University Medicine Greifswald, Greifswald, Deutschland
| | - Ralf Ewert
- Internal Medicine B, University Medicine Greifswald, Greifswald, Deutschland
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Cosmi B, Giannella M, Fornaro G, Cristini F, Patacca A, Castagna A, Mazzaferri F, Testa S, Pan A, Lupi M, Brambilla P, Montineri A, Frattima S, Bignami EG, Salvetti M, De Stefano G, Grandone E, Di Perri G, Rozzini R, Stella A, Romagnoli A, Drago F, Viale P. Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19. BMC Infect Dis 2023; 23:718. [PMID: 37875792 PMCID: PMC10594805 DOI: 10.1186/s12879-023-08297-7] [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: 07/27/2022] [Accepted: 04/30/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.
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Affiliation(s)
- B Cosmi
- Angiology and Blood Coagulation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni, 15, Bologna, Italy.
- Angiology and Blood Coagulation Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - M Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy
| | - G Fornaro
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy.
| | - F Cristini
- Infectious Disease Unit, Forlì and Cesena Hospiitals, Forlì-Cesena, Italy
| | - A Patacca
- Infectious Disease Unit, Forlì and Cesena Hospiitals, Forlì-Cesena, Italy
| | - A Castagna
- Clinica di Malattie Infettive, Università Vita-Salute, IRCCS San Raffaele Hospital, Milan, Italy
| | - F Mazzaferri
- Division of Infectious Diseases, Department of Medicine, Verona University Hospital, Verona, Italy
| | - S Testa
- Haemostasis and Thrombosis Center, ASST Cremona, Cremona, Italy
| | - A Pan
- Infectious Disease Unit, ASST Cremona, Cremona, Italy
| | - M Lupi
- Infectious Disease Unit, ASST Cremona, Cremona, Italy
| | - P Brambilla
- Infectious Disease Unit, ASST Cremona, Cremona, Italy
| | | | | | - E G Bignami
- Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - M Salvetti
- ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy
| | | | - E Grandone
- Fondazione "Casa Sollievo della Sofferenza" San Giovanni Rotondo, Department Medical and Surgical Sciences, University of Foggia, Foggia, Italy
- Ob/Gyn First Sechenov University, Moscow, Russia
| | | | - R Rozzini
- Dipartimento di Geraitria, Unità di cura subintensiva- Unità di Geriatria per Acuti, Unità di attività subacute,Poliambulanza Hospital, Brescia, Italy
| | - A Stella
- Department of Speciality Diagnostics and Experimental Medicine (DIMES), Sant'Orsola Hospital University of Bologna, Bologna, Italy
| | | | - F Drago
- University of Catania (UNICT), Catania, Italy
| | - P Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy
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12
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Krupp J, Menon A, Shauly O, Losken A. Reflecting upon the Long-term Impact of COVID-19 on Cosmetic Plastic Surgery and Education. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2023; 11:e5359. [PMID: 37850209 PMCID: PMC10578663 DOI: 10.1097/gox.0000000000005359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/11/2023] [Indexed: 10/19/2023]
Abstract
As we enter a new year, this article serves as an opportunity to ponder on the impact of a worldwide pandemic on physicians and the field of plastic surgery, which began 4 years ago in January 2020. When looking at the data in the general-surgery and reconstructive literature, the surgical treatment of patients with COVID-19 appears safest 8 weeks after infection. It was also found that the so-called Zoom-boom crush of cosmetic surgery cases following pandemic lockdown appeared to be largely due to a backlog of cases. Cosmetic surgery, particularly facial cosmetic surgery, continues to increase in popularity year over year. However, the effects on plastic surgery training remain unclear. Even so, those affected by the pandemic seem more driven than ever to find job stability and security.
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Affiliation(s)
- James Krupp
- From the Division of Plastic and Reconstructive Surgery, Emory University, Atlanta, Ga
| | - Ambika Menon
- School of Medicine, Emory University, Atlanta, Ga
| | - Orr Shauly
- From the Division of Plastic and Reconstructive Surgery, Emory University, Atlanta, Ga
| | - Albert Losken
- From the Division of Plastic and Reconstructive Surgery, Emory University, Atlanta, Ga
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13
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Maev IV, Osadchuk MA. [Diseases of the gastrointestinal tract in the context of COVID-19 infection: present and future challenges: A review]. TERAPEVT ARKH 2023; 95:586-590. [PMID: 38159010 DOI: 10.26442/00403660.2023.07.202282] [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: 09/29/2023] [Accepted: 09/29/2023] [Indexed: 01/03/2024]
Abstract
A significant prevalence of gastrointestinal symptoms in SARS-CoV-2 infection is also associated with its fecal-oral transmission, which leads to a progressive increase in the number of patients with diseases of the esophagus, stomach and intestines. In addition, intestinal infections caused by SARS-CoV-2 may be one of the main causes of functional long-term stress-related gastrointestinal disorders, united in the concept of post-COVID syndrome.
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Affiliation(s)
- I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - M A Osadchuk
- Sechenov First Moscow State Medical University (Sechenov University)
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14
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Gama-Almeida MC, Pinto GDA, Teixeira L, Hottz ED, Ivens P, Ribeiro H, Garrett R, Torres AG, Carneiro TIA, Barbalho BDO, Ludwig C, Struchiner CJ, Assunção-Miranda I, Valente APC, Bozza FA, Bozza PT, Dos Santos GC, El-Bacha T. Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19. Metabolites 2023; 13:879. [PMID: 37512587 PMCID: PMC10384698 DOI: 10.3390/metabo13070879] [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: 06/12/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
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Affiliation(s)
- Marcos C Gama-Almeida
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Gabriela D A Pinto
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Lívia Teixeira
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-361, Brazil
| | - Eugenio D Hottz
- Laboratory of Immunothrombosis, Department of Biochemistry, Federal University of Juiz de Fora, Juiz de Fora 36936-900, Brazil
| | - Paula Ivens
- LabMeta, Metabolomics Laboratory, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
| | - Hygor Ribeiro
- LabMeta, Metabolomics Laboratory, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
- Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
| | - Rafael Garrett
- LabMeta, Metabolomics Laboratory, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
| | - Alexandre G Torres
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
- Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
| | - Talita I A Carneiro
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Bianca de O Barbalho
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Christian Ludwig
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2SQ, UK
| | - Claudio J Struchiner
- School of Applied Mathematics, Fundação Getúlio Vargas, Rio de Janeiro 22231-080, Brazil
- Institute of Social Medicine, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, Brazil
| | - Iranaia Assunção-Miranda
- LaRIV, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Ana Paula C Valente
- National Center for Nuclear Magnetic Resonance-Jiri Jonas, Institute of Medical Biochemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
| | - Fernando A Bozza
- National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil
- D'Or Institute for Research and Education, Rio de Janeiro 22281-100, Brazil
| | - Patrícia T Bozza
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-361, Brazil
| | - Gilson C Dos Santos
- LabMet-Laboratory of Metabolomics, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
| | - Tatiana El-Bacha
- LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
- Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil
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Grubišić B, Švitek L, Ormanac K, Sabo D, Mihaljević I, Bilić-Ćurčić I, Omanović Kolarić T. Molecular Mechanisms Responsible for Diabetogenic Effects of COVID-19 Infection-Induction of Autoimmune Dysregulation and Metabolic Disturbances. Int J Mol Sci 2023; 24:11576. [PMID: 37511334 PMCID: PMC10380525 DOI: 10.3390/ijms241411576] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/16/2023] [Accepted: 07/16/2023] [Indexed: 07/30/2023] Open
Abstract
The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease and higher mortality rates. Interestingly, recent findings suggest a reciprocal relationship between COVID-19 and diabetes, wherein COVID-19 may contribute to developing new-onset diabetes and worsen existing metabolic abnormalities. This narrative review aims to shed light on the intricate molecular mechanisms underlying the diabetogenic effects of COVID-19. Specifically, the review explores the potential role of various factors, including direct damage to β-cells, insulin resistance triggered by systemic inflammation, and disturbances in hormonal regulation, aiming to enhance our understanding of the COVID-19 impact on the development and progression of diabetes. By analysing these mechanisms, the aim is to enhance our understanding of the impact of COVID-19 on the development and progression of diabetes. The binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) receptors, which are present in key metabolic organs and tissues, may interfere with glucometabolic pathways, leading to hyperglycaemia, and potentially contribute to the development of new disease mechanisms. The virus's impact on β-cells through direct invasion or systemic inflammation may induce insulin resistance and disrupt glucose homeostasis. Furthermore, glucocorticoids, commonly used to treat COVID-19, may exacerbate hyperglycaemia and insulin resistance, potentially contributing to new-onset diabetes. The long-term effects of COVID-19 on glucose metabolism are still unknown, necessitating further research into the possibility of developing a novel type of diabetes. This article provides a comprehensive overview of the current understanding of the interaction between COVID-19 and diabetes, highlighting potential areas for future research and therapeutic interventions.
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Affiliation(s)
- Barbara Grubišić
- Department of Infectious Diseases, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Luka Švitek
- Department of Infectious Diseases, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Klara Ormanac
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Dea Sabo
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Ivica Mihaljević
- Clinical Institute of Nuclear Medicine and Radiation Protection, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Department for Nuclear Medicine and Oncology, Faculty of Medicine, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Academy of Medical Sciences of Croatia, 15 Kaptol Street, HR-10000 Zagreb, Croatia
| | - Ines Bilić-Ćurčić
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Department of Endocrinology and Metabolism Disorders, Internal Medicine Clinic, University Hospital Centre Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
| | - Tea Omanović Kolarić
- Department of Pharmacology, Faculty of Medicine Osijek, J. J. Strossmayer University of Osijek, 4 Josip Huttler Street, HR-31000 Osijek, Croatia
- Faculty of Dental Medicine and Health Osijek, University of Osijek, 21 Crkvena Street, HR-31000 Osijek, Croatia
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16
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Niculae CM, Gorea ME, Tirlescu LG, Constantin RA, Moroti R, Hristea A. Pulmonary Thrombosis despite Therapeutic Anticoagulation in COVID-19 Pneumonia: A Case Report and Literature Review. Viruses 2023; 15:1535. [PMID: 37515221 PMCID: PMC10386232 DOI: 10.3390/v15071535] [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: 06/28/2023] [Revised: 07/10/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.
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Affiliation(s)
- Cristian-Mihail Niculae
- Infectious Diseases Department, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 050474 Bucharest, Romania
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Maria-Evelina Gorea
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Laura-Georgiana Tirlescu
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Rares-Alexandru Constantin
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Ruxandra Moroti
- Infectious Diseases Department, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 050474 Bucharest, Romania
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Adriana Hristea
- Infectious Diseases Department, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 050474 Bucharest, Romania
- National Institute for Infectious Diseases "Prof. Dr. Matei Bals", 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
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17
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Niculae CM, Hristea A, Albulescu AS, Petre VB, Anghel AMJ, Damalan AC, Bel AA, Lazar M. Quantitative chest CT imaging characteristics and outcome of patients with COVID-19 associated pulmonary artery thrombosis: A single-center retrospective cohort study. Medicine (Baltimore) 2023; 102:e34250. [PMID: 37417640 PMCID: PMC10328685 DOI: 10.1097/md.0000000000034250] [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: 03/09/2023] [Revised: 05/20/2023] [Accepted: 06/16/2023] [Indexed: 07/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19)-associated pulmonary thrombotic events occur frequently and are associated with disease severity and worse clinical outcomes. We aimed to describe the clinical and quantitative chest computed tomography (CT) imaging characteristics based on density ranges (Hounsfield units) and the outcomes of patients with COVID-19 associated pulmonary artery thrombosis. This retrospective cohort study included all patients with COVID-19 hospitalized in a tertiary care hospital between March 2020 and June 2022 who underwent a CT pulmonary angiography. We included 73 patients: 36 (49.3%) with and 37 (50.7%) without pulmonary artery thrombosis. The in-hospital all-cause mortality was 22.2 versus 18.9% ( P = .7), and the intensive care unit admission rates were 30.5 versus 8.1% ( P = .01) at the time of diagnosis of pulmonary artery thrombosis. Except for D-dimers (median of 3142 vs 533, P = .002), the other clinical, coagulopathy, and inflammatory markers were similar. Logistic regression analysis revealed that only D-dimers were associated with pulmonary artery thrombosis ( P = .012). ROC curve analysis of D-dimers showed that a value greater than 1716 ng/mL predicted pulmonary artery thrombosis with an area under the curve of 0.779, 72.2% sensitivity, and 73% specificity (95% CI 0.672-0.885). Peripheral distribution of pulmonary artery thrombosis was recorded in 94.5% of cases. In the lower lobes of the lungs, the incidence of pulmonary artery thrombosis was 6 times higher than that in the upper lobes (58-64%), with a percentage of lung injury of 80% to 90%. Analysis of the distribution of arterial branches with filling defects revealed that 91.6% occurred in lung areas with inflammatory lesions. Quantitative chest CT imaging provides valuable information regarding the extent of COVID-19 associated lung damage and can be used to anticipate the co-location of pulmonary immunothrombotic events. In patients with severe COVID-19, in-hospital all-cause mortality was similar regardless of the presence of associated distal pulmonary thrombosis.
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Affiliation(s)
- Cristian-Mihail Niculae
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
| | - Adriana Hristea
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
| | | | - Vladimir Bogdan Petre
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
| | | | - Anca-Cristina Damalan
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
| | - Adela-Abigaela Bel
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
| | - Mihai Lazar
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
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18
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Kornblith LZ, Sadhanandhan B, Arun S, Long R, Johnson AJ, Noll J, Ramchand CN, Olynyk JK, Farrell DH. γ' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity. Blood Cells Mol Dis 2023; 101:102746. [PMID: 37150704 PMCID: PMC10147444 DOI: 10.1016/j.bcmd.2023.102746] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 04/21/2023] [Accepted: 04/24/2023] [Indexed: 05/09/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO2). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95 % CI 64.8-74.8) mg/dL compared with 36.9 (95 % CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO2 ≤ 93 %, GPF 75.2 (95 % CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO2 > 93 %, GPF 62.5 (95 % CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95 % CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.
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Affiliation(s)
- Lucy Z Kornblith
- Department of Surgery, University of California, San Francisco, CA, USA
| | | | | | - Rebecca Long
- Fiona Stanley Fremantle Hospital Group, Murdoch, Western Australia, Australia; Edith Cowan University, Joondalup, Western Australia, Australia
| | - Alicia J Johnson
- Department of Surgery, Oregon Health & Science University, Portland, OR, USA
| | | | | | - John K Olynyk
- Curtin Medical School, Curtin University, Bentley, Western Australia, Australia; Department of Gastroenterology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - David H Farrell
- Department of Surgery, Oregon Health & Science University, Portland, OR, USA.
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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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20
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Marginean CM, Cinteza E, Vasile CM, Popescu M, Biciusca V, Docea AO, Mitrut R, Popescu MS, Mitrut P. Features of Liver Injury in COVID-19 Pathophysiological, Biological and Clinical Particularities. GASTROENTEROLOGY INSIGHTS 2023; 14:156-169. [DOI: 10.3390/gastroent14020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
The outbreak of the coronavirus pandemic in March 2020 has caused unprecedented pressure on public health and healthcare. The spectrum of COVID-19 onset is large, from mild cases with minor symptoms to severe forms with multi-organ dysfunction and death. In COVID-19, multiple organ damage has been described, including lung damage, acute kidney injury, liver damage, stroke, cardiovascular and digestive tract disorders. The aspects of liver injury are different, sometimes presenting with only a slight increase in liver enzymes, but sometimes with severe liver injury, leading to acute liver failure requiring liver transplantation. In patients with chronic liver disease, especially liver cirrhosis, immune dysfunction can increase the risk of infection. Immune dysfunction has a multifactorial physiopathological mechanism, implying a complement system and macrophage activation, lymphocyte and neutrophil activity dysfunction, and intestinal dysbiosis. This review aims to evaluate the most relevant studies published in the last years related to the etiopathogenetic, biochemical, and histological aspects of liver injury in patients diagnosed with COVID-19. Liver damage is more evident in patients with underlying chronic liver disease, with a significantly higher risk of developing severe outcomes of COVID-19 and death. Systemic inflammation, coagulation disorders, endothelial damage, and immune dysfunction explain the pathogenic mechanisms involved in impaired liver function. Although various mechanisms of action of SARS-CoV-2 on the liver cell have been studied, the impact of the direct viral effect on hepatocytes is not yet established.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Eliza Cinteza
- Pediatrics Department, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
| | - Corina Maria Vasile
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
- Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital, 33600 Pessac, France
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Viorel Biciusca
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Marian Sorin Popescu
- Ph.D. School Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitrut
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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21
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Niculae CM, Hristea A, Moroti R. Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review. Biomedicines 2023; 11:929. [PMID: 36979908 PMCID: PMC10045826 DOI: 10.3390/biomedicines11030929] [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: 02/28/2023] [Revised: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 03/19/2023] Open
Abstract
COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated "cytokine storm", platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.
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Affiliation(s)
- Cristian-Mihail Niculae
- Infectious Diseases Department, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (A.H.); (R.M.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Adriana Hristea
- Infectious Diseases Department, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (A.H.); (R.M.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
| | - Ruxandra Moroti
- Infectious Diseases Department, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (A.H.); (R.M.)
- National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, 1 Calistrat Grozovici Street, 021105 Bucharest, Romania
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22
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Mehak FNU, Deepak FNU, Panjwani GAR. Comment on: High incidence of pulmonary thromboembolism in hospitalized SARS-CoV-2 infected patients despite thromboprophylaxis. Heart Lung 2023. [PMCID: PMC10015087 DOI: 10.1016/j.hrtlng.2023.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Affiliation(s)
- FNU Mehak
- Ghulam Muhammad Mahar Medical college, Sukkur, Medicine, Sukkur, Pakistan,Corresponding author
| | - FNU Deepak
- Ghulam Muhammad Mahar Medical college, Sukkur, Medicine, Sukkur, Pakistan
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23
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Akácsos-Szász OZ, Pál S, Nyulas KI, Nemes-Nagy E, Fárr AM, Dénes L, Szilveszter M, Bán EG, Tilinca MC, Simon-Szabó Z. Pathways of Coagulopathy and Inflammatory Response in SARS-CoV-2 Infection among Type 2 Diabetic Patients. Int J Mol Sci 2023; 24:4319. [PMID: 36901751 PMCID: PMC10001503 DOI: 10.3390/ijms24054319] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/14/2023] [Accepted: 02/18/2023] [Indexed: 02/24/2023] Open
Abstract
Chronic inflammation and endothelium dysfunction are present in diabetic patients. COVID-19 has a high mortality rate in association with diabetes, partially due to the development of thromboembolic events in the context of coronavirus infection. The purpose of this review is to present the most important underlying pathomechanisms in the development of COVID-19-related coagulopathy in diabetic patients. The methodology consisted of data collection and synthesis from the recent scientific literature by accessing different databases (Cochrane, PubMed, Embase). The main results are the comprehensive and detailed presentation of the very complex interrelations between different factors and pathways involved in the development of arteriopathy and thrombosis in COVID-19-infected diabetic patients. Several genetic and metabolic factors influence the course of COVID-19 within the background of diabetes mellitus. Extensive knowledge of the underlying pathomechanisms of SARS-CoV-2-related vasculopathy and coagulopathy in diabetic subjects contributes to a better understanding of the manifestations in this highly vulnerable group of patients; thus, they can benefit from a modern, more efficient approach regarding diagnostic and therapeutic management.
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Affiliation(s)
- Orsolya-Zsuzsa Akácsos-Szász
- Doctoral School, Faculty of Medicine, George Emil Palade University of Medicine Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu-Mureș, Romania
| | - Sándor Pál
- Department of Transfusion Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Kinga-Ilona Nyulas
- Doctoral School, Faculty of Medicine, George Emil Palade University of Medicine Pharmacy, Science, and Technology of Târgu Mureş, 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 Mureş, 540142 Târgu-Mureș, Romania
| | - Ana-Maria Fárr
- Department of Pathophysiology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu-Mureș, Romania
| | - Lóránd Dénes
- Department of Anatomy, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu-Mureș, Romania
| | - Mónika Szilveszter
- Clinic of Plastic Surgery, Mureș County Emergency Hospital, 540136 Târgu Mureș, Romania
| | - Erika-Gyöngyi Bán
- Department of Pharmacology, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu-Mureș, Romania
| | - 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 Mureş, 540142 Târgu-Mureș, Romania
| | - Zsuzsánna Simon-Szabó
- Department of Pathophysiology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 540142 Târgu-Mureș, Romania
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24
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Vásquez-Guillén M, Vásquez-Guillén A, Inglessis-Aguilar JA, Contreras M, Carrero Y. Complicaciones Cardiovasculares asociadas a infección por SARS-CoV-2. Revisión Sistemática. KASMERA 2023. [DOI: 10.56903/kasmera.5137658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
El COVID-19 es una enfermedad que ha afectado a la población mundial, convirtiéndose en una de las peores pandemias de nuestra generación, representando un reto social y sanitario sin precedentes; afecta principalmente el sistema respiratorio, sin embargo, diversos estudios han demostrado el compromiso cardiovascular, generando preocupación, que se traduce en una mayor vulnerabilidad en los pacientes con patologías cardiovasculares subyacentes. Se ha establecido que la presencia de comorbilidades, como hipertensión, diabetes y enfermedad arterial coronaria, se asocian con tasas de mortalidad elevadas, afectando a pacientes cardiovasculares crónicos y causando alteraciones cardiovasculares en pacientes sin antecedentes, por lo cual es necesario el monitoreo de biomarcadores cardíacos para un mejor abordaje de la enfermedad. Estudios clínicos han evidenciado que la patología cardiovascular que principalmente se asocia al COVID-19 es la insuficiencia cardíaca (IC), que se manifiesta con un aumento en los niveles de troponina, miopericarditis, shock cardiogénico, lesión cardíaca aguda, trastornos de coagulación y trombosis, arritmias, además del síndrome coronario agudo y la enfermedad de Kawasaki. Este artículo es una revisión de las complicaciones cardíacas asociadas al COVID-19 y sus posibles mecanismos de acción, que permitan un mejor entendimiento por parte del personal médico y de salud (PROSPERO ID 316364).
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Affiliation(s)
- María Vásquez-Guillén
- Universidad de Los Andes. Facultad de Medicina. Departamento de Microbiología. Mérida-Mérida. Venezuela
| | - Andrea Vásquez-Guillén
- Universidad de Los Andes. Facultad de Medicina. Departamento de Microbiología. Mérida-Mérida. Venezuela
| | | | - Mike Contreras
- Universidad Federal de Goiás. Campus Colemar Natal e Silva. Instituto de Patologia Tropical e Saúde Publica. Área de imunologia. Goiânia-Goiás. Brasil
| | - Yenddy Carrero
- Universidad Técnica de Ambato. Facultad de Ciencias de la Salud. Carrera de Medicina. Campus Ingahurco. Ambato-Tungurahua. Ecuador
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25
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Al-Rawi TSS, Al-Ani RM. Liver dysfunction-related COVID-19: A narrative review. World J Meta-Anal 2023; 11:5-17. [DOI: 10.13105/wjma.v11.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/14/2022] [Indexed: 01/11/2023] Open
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26
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Nogueira RS, Salu BR, Nardelli VG, Bonturi CR, Pereira MR, de Abreu Maffei FH, Cilli EM, Oliva MLV. A snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time. Thromb J 2023; 21:1. [PMID: 36593467 PMCID: PMC9806807 DOI: 10.1186/s12959-022-00436-5] [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: 07/05/2022] [Accepted: 11/18/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND (p-BthTX-I)2 K, a dimeric analog peptide derived from the C-terminal region of phospholipase A2-like bothropstoxin-I (p-BthTX-I), is resistant to plasma proteolysis and inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains with weak cytotoxic effects. Complications of SARS-CoV-2 infection include vascular problems and increased risk of thrombosis; therefore, studies to identify new drugs for treating SARS-CoV-2 infections that also inhibit thrombosis and minimize the risk of bleeding are required. OBJECTIVES To determine whether (p-BthTX-I)2 K affects the hemostatic system. METHODS Platelet aggregation was induced by collagen, arachidonic acid, and adenosine diphosphate (ADP) in the Chronolog Lumi-aggregometer. The coagulation activity was evaluated by determining activated partial thromboplastin clotting time (aPTT) and prothrombin time (PT) with (p-BthTX-I)2 K (5.0-434.5 µg) or 0.9% NaCl. Arterial thrombosis was induced with a 540 nm laser and 3.5-20 mg kg- 1 Rose Bengal in the carotid artery of male C57BL/6J mice using (p-BthTX-I)2 K. Bleeding time was determined in mouse tails immersed in saline at 37 °C after (p-BthTX-I)2 K (4.0 mg/kg and 8.0 mg/kg) or saline administration. RESULTS (p-BthTX-I)2 K prolonged the aPTT and PT by blocking kallikrein and FXa-like activities. Moreover, (p-BthTX-I)2 K inhibited ADP-, collagen-, and arachidonic acid-induced platelet aggregation in a dose-dependent manner. Further, low concentrations of (p-BthTX-I)2 K extended the time to artery occlusion by the formed thrombus. However, (p-BthTX-I)2 K did not prolong the bleeding time in the mouse model of arterial thrombosis. CONCLUSION These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)2 K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.
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Affiliation(s)
- Ruben Siedlarczyk Nogueira
- grid.411249.b0000 0001 0514 7202Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), SP 04044- 020 São Paulo, Brazil
| | - Bruno Ramos Salu
- grid.411249.b0000 0001 0514 7202Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), SP 04044- 020 São Paulo, Brazil
| | - Vinícius Goulart Nardelli
- grid.411249.b0000 0001 0514 7202Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), SP 04044- 020 São Paulo, Brazil
| | - Camila Ramalho Bonturi
- grid.411249.b0000 0001 0514 7202Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), SP 04044- 020 São Paulo, Brazil
| | - Marina Rodrigues Pereira
- grid.410543.70000 0001 2188 478XDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, Universidade Estadual Paulista (UNESP), SP 14800-060 São Paulo, Araraquara, Brazil
| | - Francisco Humberto de Abreu Maffei
- grid.410543.70000 0001 2188 478XDepartment of Surgery and Orthopedics, Universidade Estadual Paulista (UNESP), 18618-687 São Paulo, Botucatu, SP Brazil
| | - Eduardo Maffud Cilli
- grid.410543.70000 0001 2188 478XDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, Universidade Estadual Paulista (UNESP), SP 14800-060 São Paulo, Araraquara, Brazil
| | - Maria Luiza Vilela Oliva
- grid.411249.b0000 0001 0514 7202Department of Biochemistry, Universidade Federal de São Paulo (UNIFESP), SP 04044- 020 São Paulo, Brazil
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History of COVID-19 infection is not associated with increased D-dimer levels and risk of deep-vein thrombosis in total joint arthroplasty. Arch Orthop Trauma Surg 2023; 143:785-789. [PMID: 34546422 PMCID: PMC8453476 DOI: 10.1007/s00402-021-04181-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Accepted: 09/09/2021] [Indexed: 11/09/2022]
Abstract
INTRODUCTION In the acute phase of COVID-19, elevated D-dimer levels indicate a hypercoagulable state putting the patients at increased risk for venous thromboembolic disease (VTE). It is unclear, if prior COVID-19 disease increases the risk for VTE after total joint arthroplasty (TJA) and if D-dimer levels can be used to identify patients at risk. MATERIALS AND METHODS D-Dimer levels of 313 consecutive SARS-CoV-2 IgG-positive and 2,053 -negative patients undergoing TJA between 05/20 and 12/20 were evaluated. D-Dimer levels were divided into three groups: < 200 ng/ml, 200-400 ng/ml, and > 400 ng/ml D-dimer units (DDU). 277 SARS-CoV-2 IgG-positive patients underwent a Doppler ultrasound to rule out deep-vein thrombosis (DVT) 4-6 weeks after TJA. RESULTS D-Dimer levels did not differ significantly between SARS-CoV-2 IgG-positive and -negative patients (p value 0.53). Among SARS-CoV-2 IgG-negative patients, 1687 (82.17%) had D-dimer levels < 200 ng/ml, 256 (12.47%) between 200 and 400 ng/ml, and 110 (5.36%) > 400 ng/ml. Of the SARS-CoV-2 IgG-positive patients, 257 (83.71%) had D-dimer levels < 200 ng/ml, 34 (11.07%) between 200 and 400 ng/ml, and 16 (5.21%) > 400 ng/ml. A postoperative DVT was detected in nine patients (2.9%) in the SARS-CoV-2 IgG-positive group and a PE in one patient (0.3%). 7/229 patients with < 200 ng/ml (3.1%), 1/28 patients (3.6%) with 200-400 ng/ml and 1/9 patients (11.1%) with D-dimer levels > 400 ng/ml had a DVT or PE (p = 0.43). CONCLUSIONS The findings of this investigation suggest there is no difference in D-dimer levels between SARS-CoV-2 IgG-positive and -negative patients undergoing TJA. Although there is a trend for increased VTE rates with increased D-dimer levels, routine D-dimer testing is not recommended based on the current data. SARS-CoV-2 IgG-positive patients have a low risk of VTE in the current study.
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28
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Kornblith LZ, Sadhanandhan B, Arun S, Long R, Johnson AJ, Noll J, Ramchand CN, Olynyk JK, Farrell DH. Gamma' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity. RESEARCH SQUARE 2022:rs.3.rs-2160004. [PMID: 36299432 PMCID: PMC9603834 DOI: 10.21203/rs.3.rs-2160004/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO 2 ). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95% CI 64.8-74.8) mg/dL compared with 36.9 (95% CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO 2 ≤ 93%, GPF 75.2 (95% CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO 2 > 93%, GPF 62.5 (95% CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95% CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.
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Affiliation(s)
| | | | | | - Rebecca Long
- Fiona Stanley Fremantle Hospital Group, Murdoch, Western Australia, Australia and Edith Cowan University, Joondalup, Western Australia, Australia
| | | | | | | | - John K. Olynyk
- Fiona Stanley Fremantle Hospital Group, Murdoch, Western Australia, Australia and Edith Cowan University, Joondalup, Western Australia, Australia
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Kaiafa G, Savopoulos C, Karlafti E, Pantazi K, Paramythiotis D, Thomaidou E, Daios S, Ztriva E, Gionis M, Fyntanidou V, Argiriadou H, Didangelos T. Coagulation Profile of COVID-19 Patients. Life (Basel) 2022; 12:1658. [PMID: 36295093 PMCID: PMC9604860 DOI: 10.3390/life12101658] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/17/2022] [Accepted: 10/17/2022] [Indexed: 12/09/2023] Open
Abstract
Coronavirus disease is a viral infection that can affect multiple systems and be expressed with many-or no-symptoms. The viral infection begins when the virus binds to the host's receptor and from that point on, it is transmitted to the rest of the body, where it causes inflammatory reactions. Among other tissues and systems, SARS-CoV-2 impacts the coagulation system, where it triggers the immunothrombotic response. Its effects are rather intense and can lead to many complications. COVID-19-associated coagulopathy is frequently observed in hospitalized patients, especially ICU patients, and can be proven detrimental. It is usually accompanied by other complications, such as sepsis-induced coagulopathy, disseminated intravascular coagulation and venous thromboembolism. Since all these conditions lead to poor prognosis for severely ill patients, thromboprophylaxis and coagulopathy prognosis are just as important as the therapeutic handling of these patients. Since the beginning of the pandemic, many biomarkers have been considered useful when trying to assess the thrombotic risk of hospitalized patients or evaluate the severity of their situation. At the same time, many drugs have already been tested-while others are still being trialed-in order to find the optimal therapy for each urgent situation.
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Affiliation(s)
- Georgia Kaiafa
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Christos Savopoulos
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Eleni Karlafti
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Konstantina Pantazi
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Daniel Paramythiotis
- 1st Propaedeutic Surgery Department, AHEPA General University Hospital, 54621 Thessaloniki, Greece
| | - Evanthia Thomaidou
- Department of Anesthesia and Intensive Care, AHEPA University General Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Stylianos Daios
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Eleftheria Ztriva
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Michalis Gionis
- Vascular Surgery Department, General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Varvara Fyntanidou
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Helena Argiriadou
- Department of Anesthesia and Intensive Care, AHEPA University General Hospital of Thessaloniki, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
| | - Triantafyllos Didangelos
- 1st Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54621 Thessaloniki, Greece
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Muacevic A, Adler JR. Avascular Necrosis of the Hip: A Post COVID-19 Sequela. Cureus 2022; 14:e29976. [PMID: 36381920 PMCID: PMC9636587 DOI: 10.7759/cureus.29976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2022] [Indexed: 01/24/2023] Open
Abstract
A 60-year-old African American male presented to the hospital with seven months of progressively worsening left anterior hip pain with no known trauma. Two months after the pain onset, he underwent an x-ray of the pelvis with the lateral left hip, revealing dystrophic soft tissue calcification adjacent to the superolateral left acetabulum. Pain at this time was attributed to presumed sciatica vs arthritis. The patient underwent multimodal treatment for his pain without relief. In the month prior to the presentation, the patient also developed right hip pain. He then underwent a bilateral hip x-ray, revealing left femoral neck lucency suspicious for a nondisplaced fracture. CT pelvis was ordered at this time for further evaluation and demonstrated bilateral subcapital hip fractures. He was subsequently discharged from the emergency department with pending laboratory work and plans for close outpatient orthopedic surgery follow-up. The following day, the patient was instructed to return to the hospital due to an elevated erythrocyte sedimentation rate of 39 mm/hr and C-reactive protein of 41.6 mg/L. Subsequent MRI pelvis revealed bilateral subcapital femoral neck fractures with avascular necrosis (AVN) requiring surgical intervention with bilateral hip arthroplasty. Our patient underwent an extensive workup with no evidence of traditional risk factors for osteonecrosis, osteopenia, or other bone diseases. A pertinent finding in the patient's history was an admission for severe SARS-CoV-2 (COVID-19) infection 10 months prior. 'Long COVID' is a complex illness that has been shown to affect intravascular blood flow, and likely contributed to the development of bilateral hip AVN in our patient. Given this novel presentation, it is crucial that AVN be considered early in evaluating anterior hip pain for patients with a history of COVID-19 infection in order to avoid severe consequences such as femoral neck fractures.
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Al-kuraishy HM, Al-Gareeb AI, Elekhnawy E, Batiha GES. Dipyridamole and adenosinergic pathway in Covid-19: a juice or holy grail. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022; 23:140. [PMID: 37521831 PMCID: PMC9510284 DOI: 10.1186/s43042-022-00354-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 09/16/2022] [Indexed: 11/10/2022] Open
Abstract
Background Coronavirus disease 2019 (Covid-19) is an infectious worldwide pandemic triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2). This pandemic disease can lead to pro-inflammatory activation with associated acute lung injury and acute respiratory distress syndrome. Main body of the abstract SARS-CoV-2 infection is linked with inhibition of adenosine and activation of phosphodiesterase. Dipyridamole (DIP) is a nucleoside transport and phosphodiesterase inhibitor so that it may potentially affect SARS-CoV-2 infection and its accompanying inflammations. Therefore, the primary objective of this mini-review study was to elucidate the potential beneficial impacts of DIP on the adenosinergic pathway in Covid-19. A systemic search was done using online databases with relevant keywords. The findings of the present study illustrated that DIP directly or indirectly, through augmentation of adenosine and inhibition of phosphodiesterase, mitigates Covid-19 outcomes. Conclusion Our study concluded that DIP has a potential therapeutic effect in the management and treatment of Covid-19. This could be attained either directly, through anti-SARS-CoV-2, anti-inflammatory, and anti-platelets properties, or indirectly, through augmentation of extracellular adenosine, which has anti-inflammatory and immune-regulatory effects. However, extensive randomized clinical trials, and clinical and prospective research in this area are required to demonstrate the safety and therapeutic efficacy of DIP and adenosine modulators in the treatment of Covid-19.
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Affiliation(s)
- Hayder M. Al-kuraishy
- Department of Pharmacology, Toxicology and Medicine, College of Medicine, Al-Mustansiriyah University, Baghdad, 14132 Iraq
| | - Ali I. Al-Gareeb
- Department of Pharmacology, Toxicology and Medicine, College of Medicine, Al-Mustansiriyah University, Baghdad, 14132 Iraq
| | - Engy Elekhnawy
- Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, 31527 Egypt
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511 Al Beheira Egypt
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Narayan M, Leahy N, Alqunaibit D, An A, de Angelis P, Bronstein M, Eachempati S, Gibson C, Kelly A, Minneman JA, Shou J, Smith KE, Villegas C, Winchell RJ, Witenko C, Barie PS. Thrombotic Events and Anticoagulation-Related Bleeding Complications in Critically Ill Patients with Coronavirus Disease 2019. Surg Infect (Larchmt) 2022; 23:705-711. [PMID: 36083247 DOI: 10.1089/sur.2022.193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background: Thrombosis (T) is common in coronavirus disease 2019 (COVID-19) patients, and d-dimer concentrations correlate with outcomes. Controversy exists with regards to anticoagulation (AC) for patients. We implemented a full-heparinization AC protocol from the onset of the pandemic and hypothesized that a safety signal would be undetectable. Patients and Methods: Prospective evaluation of 111 patients with COVID-19 critical illness hospitalized from March to June 2020. All patients received therapeutic heparinoid-based AC from admission. Incidences of T, bleeding (B), or both (BT) were noted. The primary outcome was mortality. Kruskal-Wallis test and logistic regression were performed. Results are expressed as n (%), median (interquartile range) and odds ratios with 95% confidence intervals. Alpha was set at 0.05. Results: Thirty-two patients (28%) had T, 23 (20%) had B, and 14 (12%) had BT; 42 (40%) patients were unaffected. Two logistic regression models (outcome = mortality) evaluated BT as T, or BT as B. For BT as T, neither T, B, nor male gender predicted mortality; similarly, for BT as B, neither T, B, nor male gender predicted mortality. Factors associated with higher odds of death included higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; p = 0.0045), higher d-dimer concentration (OR, 1.00; 95% CI, 1.00-1.01; p = 0.043), and higher activated partial thromboplastin time (aPTT; OR, 1.09; 95% CI, 1.02-1.16; p = 0.010). Conclusions: Neither T nor B predicted mortality in this prospective cohort of anticoagulated patients with COVID-19 critical illness. These data support continued full-dose heparinoid prophylaxis.
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Affiliation(s)
- Mayur Narayan
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Nicole Leahy
- Trauma Program, NewYork-Presbyterian Hospital, New York, New York, USA
| | - Dalia Alqunaibit
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Anjile An
- Division of Biostatistics, Department of Population Health Sciences, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Paolo de Angelis
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Matthew Bronstein
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Soumitra Eachempati
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Cameron Gibson
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Anton Kelly
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Jennifer A Minneman
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Jian Shou
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Kira E Smith
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Cassandra Villegas
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Robert J Winchell
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
- Division of Medical Ethics, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Corey Witenko
- Department of Pharmacy, NewYork-Presbyterian Hospital, New York, New York, USA
| | - Philip S Barie
- Division of Trauma, Burns, Acute and Critical Care, Department of Surgery, Department of Medicine, Weill Cornell Medicine, New York, New York, USA
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Tiwari A, Tripathi S, Pandey DC, Sharma N, Sharma S. Detection of COVID-19 Infection in CT and X-ray images using transfer learning approach. Technol Health Care 2022; 30:1273-1286. [PMID: 36093719 DOI: 10.3233/thc-220114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND The infection caused by the SARS-CoV-2 (COVID-19) pandemic is a threat to human lives. An early and accurate diagnosis is necessary for treatment. OBJECTIVE The study presents an efficient classification methodology for precise identification of infection caused by COVID-19 using CT and X-ray images. METHODS The depthwise separable convolution-based model of MobileNet V2 was exploited for feature extraction. The features of infection were supplied to the SVM classifier for training which produced accurate classification results. RESULT The accuracies for CT and X-ray images are 99.42% and 98.54% respectively. The MCC score was used to avoid any mislead caused by accuracy and F1 score as it is more mathematically balanced metric. The MCC scores obtained for CT and X-ray were 0.9852 and 0.9657, respectively. The Youden's index showed a significant improvement of more than 2% for both imaging techniques. CONCLUSION The proposed transfer learning-based approach obtained the best results for all evaluation metrics and produced reliable results for the accurate identification of COVID-19 symptoms. This study can help in reducing the time in diagnosis of the infection.
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Affiliation(s)
- Alok Tiwari
- School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.,School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India
| | - Sumit Tripathi
- Department of Electronics and Communication Engineering, Graphic Era Deemed to be University, Dehradun, Uttarakhand, India.,School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India
| | - Dinesh Chandra Pandey
- Department of Management Studies, Graphic Era Deemed to be University, Dehradun, Uttarakhand, India
| | - Neeraj Sharma
- School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India
| | - Shiru Sharma
- School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India
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Taha MM, Taha MM, Al Menshawy HA, Elsharkawy AM. Cerebral venous sinus thrombosis in COVID 19 patients: Report of 2 cases. INTERDISCIPLINARY NEUROSURGERY 2022; 29:101599. [PMID: 35692246 PMCID: PMC9167686 DOI: 10.1016/j.inat.2022.101599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 05/13/2022] [Accepted: 05/30/2022] [Indexed: 01/07/2023] Open
Abstract
Background Initially, novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was considered primarily a respiratory pathogen. However, with time it has behaved as a virus with the potential to cause multi-system involvement, including neurological manifestations which varies from acute to subacute onset of headache, seizures, a decrease of consciousness, and paralysis. Case description Two cases of cerebral sinus venous thrombosis in COVID-19 patients were reported, following respiratory disorders, which was triggered by the SARS-CoV-2 infection. The first patient, presented with a decrease in level of consciousness and hemiparesis, was 23 years old female having no history of previous medical co-morbidities. The latter case, 21 years old woman showed less severe presentations of COVID-19 associated with headache, vomiting and papilledema. These two cases marvellously improved with no neurological deficit with aggressive course of anticoagulation. Conclusion CVST should be suspected in COVID-19 patients presenting with headache, paralysis, aphasia or seizures. The high mortality rate of CVST in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.
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Affiliation(s)
- Mahmoud M Taha
- Department of Neurosurgery, Zagazig University, Zagazig, Egypt
| | - Mazen M Taha
- Faculty of Medicine, Zagazig University, Zagazig, Egypt
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Kell DB, Pretorius E. The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications. Biochem J 2022; 479:1653-1708. [PMID: 36043493 PMCID: PMC9484810 DOI: 10.1042/bcj20220154] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 02/07/2023]
Abstract
Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
| | - Etheresia Pretorius
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
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Yi J, Miao J, Zuo Q, Owusu F, Dong Q, Lin P, Wang Q, Gao R, Kong X, Yang L. COVID-19 pandemic: A multidisciplinary perspective on the pathogenesis of a novel coronavirus from infection, immunity and pathological responses. Front Immunol 2022; 13:978619. [PMID: 36091053 PMCID: PMC9459044 DOI: 10.3389/fimmu.2022.978619] [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: 06/26/2022] [Accepted: 08/04/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), has spread to more than 200 countries and regions, having a huge impact on human health, hygiene, and economic activities. The epidemiological and clinical phenotypes of COVID-19 have increased since the onset of the epidemic era, and studies into its pathogenic mechanisms have played an essential role in clinical treatment, drug development, and prognosis prevention. This paper reviews the research progress on the pathogenesis of the novel coronavirus (SARS-CoV-2), focusing on the pathogenic characteristics, loci of action, and pathogenic mechanisms leading to immune response malfunction of SARS-CoV-2, as well as summarizing the pathological damage and pathological manifestations it causes. This will update researchers on the latest SARS-CoV-2 research and provide directions for future therapeutic drug development.
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Affiliation(s)
- Jia Yi
- College of Traditional Chinese medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Jiameng Miao
- College of Traditional Chinese medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qingwei Zuo
- Research Center for Infectious Diseases, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Felix Owusu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qiutong Dong
- College of Traditional Chinese medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Peizhe Lin
- College of Traditional Chinese medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qilong Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Gao
- Institute of Clinical Pharmacology of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xianbin Kong
- College of Traditional Chinese medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Long Yang
- Research Center for Infectious Diseases, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Motloch LJ, Jirak P, Mirna M, Fiedler L, Davtyan PA, Lakman IA, Gareeva DF, Tyurin AV, Gumerov RM, Matskeplishvili ST, Pavlov VN, Cai B, Kopp K, Topf A, Hoppe UC, Pistulli R, Zagidullin NS. Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors. Front Cardiovasc Med 2022; 9:916156. [PMID: 35966512 PMCID: PMC9372296 DOI: 10.3389/fcvm.2022.916156] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/11/2022] [Indexed: 11/21/2022] Open
Abstract
Introduction Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting. Methods To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period. Results While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = −3.33 (0.60), P < 0.001 and dipyridamole: B = −3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = −2.69 (0.74), P < 0.001 and dipyridamole: B = −17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B−3.12 (1.42), P = 0.012] and stroke [B = −3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = −17.05 (1.01), P < 0.001]. Conclusion Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.
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Affiliation(s)
- Lukas J. Motloch
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
- *Correspondence: Lukas J. Motloch
| | - Peter Jirak
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Moritz Mirna
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Lukas Fiedler
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
- Department of Internal Medicine, Cardiology, Nephrology and Intensive Care Medicine, Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Paruir A. Davtyan
- Department of Internal Medicine I, Bashkir State Medical University, Ufa, Russia
| | - Irina A. Lakman
- Department of Internal Medicine I, Bashkir State Medical University, Ufa, Russia
- Scientific Laboratory for the Study of Socio-Economic Problems of the Regions Bashkir State University, Ufa, Russia
| | - Diana F. Gareeva
- Department of Internal Medicine I, Bashkir State Medical University, Ufa, Russia
| | - Anton V. Tyurin
- Department of Internal Diseases II, Bashkir State Medical University, Ufa, Russia
| | - Ruslan M. Gumerov
- Department of Internal Medicine I, Bashkir State Medical University, Ufa, Russia
| | | | | | - Benzhi Cai
- Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, China
| | - Kristen Kopp
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Albert Topf
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Uta C. Hoppe
- Clinic II for Internal Medicine, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Rudin Pistulli
- Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Munster, Munster, Germany
| | - Naufal S. Zagidullin
- Department of Internal Medicine I, Bashkir State Medical University, Ufa, Russia
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Battaglini D, Premraj L, Griffee M, Huth S, Fanning J, Whitman G, Bastos Porto D, Arora R, Durham L, Gnall E, Amato M, Williams V, Noel A, De Franca SA, Samoukovic G, Pujo B, Kent D, Marwali E, Al-Fares A, Stecher SS, Panigada M, Giani M, Foti G, Pelosi P, Pesenti A, White NM, Li Bassi G, Suen J, Fraser JF, Robba C, Cho SM. Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study. Front Med (Lausanne) 2022; 9:930217. [PMID: 35935771 PMCID: PMC9355612 DOI: 10.3389/fmed.2022.930217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 06/06/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number ACTRN12620000421932.
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Affiliation(s)
- Denise Battaglini
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) for Oncology and Neurosciences, Genoa, Italy
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Lavienraj Premraj
- Griffith University School of Medicine, Gold Coast, QLD, Australia
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Matthew Griffee
- Department of Anesthesiology and Perioperative Medicine, University of Utah, Salt Lake City, UT, United States
| | - Samuel Huth
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Jonathon Fanning
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Glenn Whitman
- Division of Neuroscience Critical Care, Departments of Neurology, Neurosurgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | | | - Rakesh Arora
- Section of Cardiac Surgery, Department of Surgery, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Cardiac Sciences Program, St. Boniface Hospital, Winnipeg, MB, Canada
| | - Lucian Durham
- Department of Surgery, Division of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Eric Gnall
- Division of Cardiovascular Diseases, Lankenau Medical Center and Lankenau Institute of Medical Research, Wynnewood, PA, United States
- Jefferson Medical College, Philadelphia, PA, United States
| | - Marcelo Amato
- Laboratório de Pneumologia LIM-09, Disciplina de Pneumologia, Heart Institute (Incor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Virginie Williams
- Équipe de Recherche en Soins Intensifs (ERESI), Research Centre, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur-de-Montréal, 5400 boulevard Gouin Ouest, K-3000, Montreal, QC, Canada
| | - Alexandre Noel
- Équipe de Recherche en Soins Intensifs (ERESI), Research Centre, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur-de-Montréal, 5400 boulevard Gouin Ouest, K-3000, Montreal, QC, Canada
| | - Sabrina Araujo De Franca
- Équipe de Recherche en Soins Intensifs (ERESI), Research Centre, Centre Intégré Universitaire de Santé et de Services Sociaux du Nord-de-l'île-de-Montréal, Hôpital du Sacré-Coeur-de-Montréal, 5400 boulevard Gouin Ouest, K-3000, Montreal, QC, Canada
| | - Gordan Samoukovic
- Division of Critical Care Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - Bambang Pujo
- Department of Anesthesiology and Reanimation, Dr. Soetomo Academic Hospital, Surabaya, Indonesia
| | - David Kent
- Institute for Clinical Research and Health Policy Studies, Tufts Medical Center/Tufts University School of Medicine, Boston, MA, United States
| | - Eva Marwali
- Pediatric Cardiac Intensive Care Division, National Cardiovascular Center Harapan Kita, Jakarta, Indonesia
| | - Abdulrahman Al-Fares
- Kuwait Extracorporeal Life Support Program, Ministry of Health, Kuwait City, Kuwait
- Department of Anesthesia and Critical Care Medicine, Al-Amiri Hospital, Kuwait City, Kuwait
| | - Stephanie-Susanne Stecher
- Department of Medicine 2, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
| | - Mauro Panigada
- Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Marco Giani
- Emergency Department, Azienda Socio Sanitaria Territoriale (ASST) Monza - San Gerardo Hospital, Monza, Italy
- University of Milano-Bicocca, Milan, Italy
| | - Giuseppe Foti
- Emergency Department, Azienda Socio Sanitaria Territoriale (ASST) Monza - San Gerardo Hospital, Monza, Italy
- University of Milano-Bicocca, Milan, Italy
| | - Paolo Pelosi
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) for Oncology and Neurosciences, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Antonio Pesenti
- Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Nicole Marie White
- Australian Centre for Health Services Innovation, Centre for Healthcare Transformation, School of Public Health and Social Work, Queensland University of Technology, Brisbane, QLD, Australia
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
| | - Jacky Suen
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - John F. Fraser
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia
- Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, QLD, Australia
| | - Chiara Robba
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) for Oncology and Neurosciences, Genoa, Italy
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Sung-Min Cho
- Division of Neuroscience Critical Care, Departments of Neurology, Neurosurgery, and Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Camporesi A, Gemma M, Buonsenso D, Ferrario S, Mandelli A, Pessina M, Diotto V, Rota E, Raso I, Fiori L, Campari A, Izzo F. Lung Ultrasound Patterns in Multisystem Inflammatory Syndrome in Children (MIS-C)-Characteristics and Prognostic Value. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9070931. [PMID: 35883915 PMCID: PMC9322869 DOI: 10.3390/children9070931] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 05/31/2022] [Accepted: 06/15/2022] [Indexed: 12/11/2022]
Abstract
Objective and design: Following COVID-19 infection, children can develop an hyperinflammatory state termed Multisystem Inflammatory Syndrome in Children (MIS-C). Lung Ultrasound (LUS) features of COVID-19 in children have been described, but data describing the LUS findings of MIS-C are limited. The aim of this retrospective observational study conducted between 1 March and 31 December 2020, at a tertiary pediatric hospital in Milano, is to describe LUS patterns in patients with MIS-C and to verify correlation with illness severity. The secondary objective is to evaluate concordance of LUS with Chest X-ray (CXR). Methodology: Clinical and laboratory data were collected for all patients (age 0−18 years) admitted with MIS-C, as well as LUS and CXR patterns at admission. PICU admission, needed for respiratory support and inotrope administration, hospital, and PICU length of stay, were considered as outcomes and evaluated in the different LUS patterns. An agreement between LUS and CXR evaluation was assessed with Cohen’ k. Results: 24 children, who had a LUS examination upon admission, were enrolled. LUS pattern of subpleural consolidations < or > 1 cm with or without pleural effusion were associated with worse Left Ventricular Ejection Fraction at admission and need for inotropes. Subpleural consolidations < 1 cm were also associated with PICU length of stay. Agreement of CXR with LUS for consolidations and effusion was slight. Conclusion: LUS pattern of subpleural consolidations and consolidations with or without pleural effusion are predictors of disease severity; under this aspect, LUS can be used at admission to stratify risk of severe disease.
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Affiliation(s)
- Anna Camporesi
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
- Correspondence:
| | - Marco Gemma
- Department of NeuroAnesthesia and NeuroIntensive Care, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20154 Milano, Italy;
| | - Danilo Buonsenso
- Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario “A. Gemelli”, 00168 Roma, Italy;
| | - Stefania Ferrario
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
| | - Anna Mandelli
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
| | - Matteo Pessina
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
| | - Veronica Diotto
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
| | - Elena Rota
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
| | - Irene Raso
- Department of Pediatric Cardiology, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy;
| | - Laura Fiori
- Department of Pediatrics, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy;
| | - Alessandro Campari
- Department of Pediatric Radiology, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy;
| | - Francesca Izzo
- Department of Pediatric Anesthesia and Intensive Care, Children’s Hospital “Vittore Buzzi”, 20154 Milano, Italy; (S.F.); (A.M.); (M.P.); (V.D.); (E.R.); (F.I.)
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Marchioni C, Esposito G, Calci M, Bais B, Colussi G. Effect of intermediate/high versus low dose heparin on the thromboembolic and hemorrhagic risk of unvaccinated COVID-19 patients in the emergency department. BMC Emerg Med 2022; 22:107. [PMID: 35698054 PMCID: PMC9192337 DOI: 10.1186/s12873-022-00668-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/10/2022] [Indexed: 11/10/2022] Open
Abstract
Background The optimal prophylactic dose of heparin in patients with coronavirus-associated disease 2019 (COVID-19) in the emergency department (ED) is debated. This study aimed to analyze different thromboprophylaxis approaches in unvaccinated COVID-19 patients admitted to ED without initial venous thromboembolism. Methods Retrospectively, the effect of intermediate/high versus low dose heparin treatment was evaluated from December 2020 to July 2021 in a tertiary Academic Hospital in northeast Italy. The primary outcome comprised arterial or venous thromboembolism or all-cause death within 30 days. Secondary outcomes comprised each single primary outcome component or major hemorrhagic event. Cox regression was used to determine predictors of the primary outcome and propensity score weights to balance the effect of heparin treatment on all outcomes. Results Data of 144 consecutive patients (age 70 ± 13, 33% females) were included in the study. High-dose prophylactic heparin was used in 69%, intermediate in 15%, and low in 17% of patients. The primary outcome occurred in 48 patients. Independent predictors of the primary outcome were COVID-19 severity (hazards ratio (HR) 1.96, 95% confidence interval (CI) 1.05–3.65, p = 0.035) and D-dimer levels (HR each log ng/dl 1.38, 95% CI 1.04–1.84, p = 0.026). Intermediate/high dose heparin did not affect the risk of the primary outcome compared with the low dose (weighted HR 1.39, 95% CI 0.75–2.56, p = 0.292). Intermediate/high heparin increased the risk of major hemorrhagic events (weighted HR 5.92, 95% CI 1.09–32, p = 0.039). Conclusions In unvaccinated COVID-19 patients admitted to ED, prophylaxis with heparin at the intermediate/high dose did not reduce primary outcome compared with the low dose but increased the risk of major hemorrhagic events.
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Affiliation(s)
- Claudia Marchioni
- Division of Internal Medicine and Emergency Medicine Residency Program, Department of Medicine, University of Udine, 33100, Udine, Italy
| | - Gaetano Esposito
- Department of Emergency Medicine, ASUFC University Hospital of Udine, 33100, Udine, Italy
| | - Mario Calci
- Department of Emergency Medicine, ASUFC University Hospital of Udine, 33100, Udine, Italy
| | - Bruno Bais
- Thrombosis Prevention Unit, 2nd Division of Internal Medicine, Department of Medicine, ASUFC University Hospital of Udine, 33100, Udine, Italy
| | - GianLuca Colussi
- Division of Internal Medicine and Emergency Medicine Residency Program, Department of Medicine, University of Udine, 33100, Udine, Italy.
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Săbiescu DM, Kamal AM, Kamal CK, Alexandru DO, Mitruț P. Liver damage in the context of SARS-CoV-2. Covid-19 treatment and its effects on the liver. J Med Life 2022; 15:727-734. [PMID: 35928369 PMCID: PMC9321495 DOI: 10.25122/jml-2022-0177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/16/2022] [Indexed: 11/21/2022] Open
Abstract
Since COVID-19 was declared a pandemic by the World Health Organization, the scientific community has tried to protect the population from the infection and its effects through multiple lines of evidence. Patients at high risk of developing severe disease were advised to protect themselves and practice effective physical distancing. Phenotypes specific to this infection need to be reviewed to understand COVID-19 and its clinical manifestations. When the pandemic began, the scientific community was concerned with the unfavorable outcome of cases with pre-existing liver disease. There have been speculations about risk factors for severe diseases such as liver disease, age, gender, and association with obesity or diabetes.
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Affiliation(s)
- Denisa Marilena Săbiescu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Adina Maria Kamal
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Constantin Kamal Kamal
- Department of Family Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Dragos Ovidiu Alexandru
- Department of Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Paul Mitruț
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
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Toda M, Yoshifuji A, Fujii K, Komatsu M, Kato A, Tamura I, Sugi W, Ryuzaki M. Patients with hemodialysis-induced hypoxemia had a poor prognosis of COVID-19. RENAL REPLACEMENT THERAPY 2022; 8:22. [PMID: 35615622 PMCID: PMC9122251 DOI: 10.1186/s41100-022-00408-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 05/01/2022] [Indexed: 11/21/2022] Open
Abstract
Background We experienced that some hemodialysis (HD) patients with coronavirus disease 2019 (COVID-19) exacerbated hypoxemia during HD. Though HD-induced hypoxemia has been reported, there have been no reports of HD-induced hypoxemia in patients with COVID-19 and its effect on prognosis of COVID-19. Methods Eleven HD patients admitted with COVID-19 from August 2020 to April 2021 were classified into the patients whose oxygen demand increased by more than 3 L/min with mask during HD (worsened group, n = 5) and others (not-worsened group, n = 6). The background, laboratory findings, severity of COVID-19 and prognosis were compared between the two groups. In addition, blood gases were measured before and after dialysis among HD patients admitted with COVID-19 on April 2021 (n = 3). Results There were no significant differences in backgrounds, except for a higher proportion of diabetes mellitus in worsened group (p = 0.04). Although laboratory findings were not significantly different on admission day, albumin and LDH levels 7 days after admission were significantly lower and higher in worsened group, respectively (p = 0.03 and < 0.01). The severity of COVID-19 and survival rate were significantly worse in worsened group (p = 0.01 and 0.03). The alveolar-arterial oxygen pressure difference (Aa-DO2) opened during HD in a patient with HD-induced hypoxemia, but did not open in patients without HD-induced hypoxemia. Conclusions There is a close relationship among HD-induced hypoxemia and poor prognosis of COVID-19. The HD-induced hypoxemia of patients with COVID-19 may be caused by ventilation/perfusion mismatching. Supplementary Information The online version contains supplementary material available at 10.1186/s41100-022-00408-5.
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Affiliation(s)
- Masataro Toda
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Ayumi Yoshifuji
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Kentaro Fujii
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Motoaki Komatsu
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Ai Kato
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Ikue Tamura
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Wataru Sugi
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
| | - Munekazu Ryuzaki
- Department of Nephrology, Tokyo Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073 Japan
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Smolnikova MV, Tereshchenko SY. Proteins of the lectin pathway of the complement system activation: immunobiological functions, genetics and involvement in the pathogenesis of human diseases. RUSSIAN JOURNAL OF INFECTION AND IMMUNITY 2022; 12:209-221. [DOI: 10.15789/2220-7619-pot-1777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The complement system is the most ancient components in the innate immunity, mainly functioning to primarily eliminate bacterial agents intravascularly. Moreover, the complement complex proteins play a role as a bridge between the systems of innate and adaptive immunity providing adequate conditions for maturation and differentiation of B- and T-lymphocytes. The complement system consists of plasma proteins and membrane receptors. Plasma proteins interact with each other via the three described cascade pathways lectin (which is most ancient phylogenetically), alternative and classical. Lectins are proteins comprising a separate superfamily of pattern-recognizing receptors able to sense molecules of oligo- and polysaccharide nature and induce their aggregation. Among all the lectins, ficolins (FCN) (common domain fibrinogen) and collectins (common domain collagen) mannose-binding lectin (MBL), hepatic and renal collectins have exert unique functions by complexing with carbohydrate components of microbial wall. Formation of a compound complex microbial wall polysaccharides + collectin/ficolin + specific mannose-binding lectin-associated serine proteases (MARP) results in the complement system activation, inflammatory reaction and bacterium elimination. Such scenario is proceeded along the lectin pathway compared to the two other pathways called classical and alternative. Examining a role of the complement system and congenital protein defects in the pathogenesis of various diseases is of topical interest because inborn deficiency of the complement components comprises at least 5% out of total primary immunodeficiency rate, whereas the aspects of their prevalence and pathogenesis remain unexplored. Relevance of investigating the complement system components for diverse populations is tremendous, taking into consideration accumulated evidence regarding an important role of the lectin pathway in viral infections. Lectins, the main proteins in the lectin pathway of the complement activation, are encoded by polymorphic genes, wherein single nucleotide polymorphisms (SNPs) result in altered protein conformation and expression, which, in turn, affects functionality and potential to respond to a pathogen. The distribution of the lectin polymorphic gene frequencies and their haplotypes displays extremely marked population differences. According to analyzing available data, population SNP frequencies including those associated with inborn deficiencies for components of the lectin pathway have been currently scarce or unexplored. hence, here we review major lectins and their functions, their functionally significant SNPs in diverse populations and their pathogenetic importance for host defense functions.
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Yuan Z, Pan L, Wang Y, Wang W. Continuously protracted infusion of cisatracurium besilate in patients with ARDS. Ann Med Surg (Lond) 2022; 77:103718. [PMID: 35638041 PMCID: PMC9142704 DOI: 10.1016/j.amsu.2022.103718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/27/2022] [Accepted: 05/01/2022] [Indexed: 11/29/2022] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is still associated with significant mortality, especially the elderly and those with comorbidities are at highest risk of death. Neuromuscular blocking agents (NMBAs) are used in a large but highly variable proportion of patients with ARDS. Case presentation We describe the case of one critically ill patient with serious ARDS, because of virus pneumonia. In spite of the reduced tidal volume to 4–6 mL/kg of predicted body weight (PBW) and prone position were applied timely, the irresistible progress of disease leaded to an amazing prolonged application of deep sedation and analgesia, as well as NMBA, for the purpose of lung-protective mechanical ventilation. Result The clinical and biochemical parameters guided us toward the recognition that cisatracurium, bolus of 0.1 mg/kg followed by a median infusion rate of 1.91 (1.43–9.52) μg/kg.min, combined with continuous infusion of midazolam 3.43 (2.06–6.17) mg/kg.d and remifentanil 3.79 (3.43–8.57) μg/kg.h is efficacious and suitable for continuous muscle paralysis. Conclusion The intensive care unit (ICU)-acquired weakness (ICU-AW) was inevitable. Besides, an increased demand on drug concentration with the extension of medication time was observed as well.
The continuous infusion of cisatracurium is safety and efficacy. The drug concentration of cisatracurium is time-dependent. ICU-acquired weakness (ICU-AW) is inevitable for the critical illness.
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COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients. Crit Care Explor 2022; 4:e0671. [PMID: 35372842 PMCID: PMC8966959 DOI: 10.1097/cce.0000000000000671] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19–related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)–related ARDS.
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Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 2022; 479:537-559. [PMID: 35195253 PMCID: PMC8883497 DOI: 10.1042/bcj20220016] [Citation(s) in RCA: 138] [Impact Index Per Article: 46.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 12/15/2022]
Abstract
Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
| | | | - Etheresia Pretorius
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch Private Bag X1 Matieland, 7602, South Africa
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Spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in non-ventilated COVID-19 patients. Future Sci OA 2022; 8:FSO771. [PMID: 35059221 PMCID: PMC8609960 DOI: 10.2144/fsoa-2021-0090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 11/02/2021] [Indexed: 01/08/2023] Open
Abstract
Aim: Pneumothorax (PNX), pneumomediastinum (PMD) and subcutaneous emphysema (SCE) are COVID-19 complications related to positive-pressure ventilation. We analyzed the pathophysiology of these complications without ventilation. Patients & methods: Out of 1845 admitted COVID-19 patients, we retrospectively collected data for 15 patients, from a tertiary medical center, from 1 October 2020 to 31 March 2021. Results: Five patients suffered from spontaneous PNX, 8/15 developed PMD and 8/15 developed SCE. The mean BMI was 29.7, as most patients were obese or overweight. Most patients had lymphocytopenia and increased C-reactive protein, ferritin and lactate dehydrogenase levels. Eleven patients succumbed to the disease. Conclusion: Risk factors of spontaneous PNX, PMD and SCE in COVID-19 patients need further investigations by conducting more comprehensive case–control studies. We have investigated spontaneous alveolar rupture as a complication in 15 COVID-19 patients. Manifested as pneumothorax, pneumomediastinum and subcutaneous emphysema, these complications are less common in patients without mechanical ventilation. Management of these patients was either conservative or by insertion of a chest tube. Eventually, 11 out of 15 patients have passed away due to respiratory failure.
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Chang JC. Pathogenesis of Two Faces of DVT: New Identity of Venous Thromboembolism as Combined Micro-Macrothrombosis via Unifying Mechanism Based on "Two-Path Unifying Theory" of Hemostasis and "Two-Activation Theory of the Endothelium". Life (Basel) 2022; 12:220. [PMID: 35207507 PMCID: PMC8874373 DOI: 10.3390/life12020220] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 11/16/2022] Open
Abstract
Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the venous system but with varying degree of clinical expression related to its localization and severity. The genesis of two phenotypes of DVT differing in clinical features and prognostic outcome can be identified by their unique hemostatic mechanisms. Two recently proposed hemostatic theories in vivo have clearly defined the character between "microthrombi" and "macrothrombus" in the vascular system. Phenotypic expression of thrombosis depends upon two major variables: (1) depth of vascular wall damage and (2) extent of the injury affecting the vascular tree system. Vascular wall injury limited to endothelial cells (ECs) in sepsis produces "disseminated" microthrombi, but intravascular injury due to trauma extending from ECs to subendothelial tissue (SET) produces "local" macrothrombus. Pathogen-induced sepsis activates the complement system leading to generalized endotheliopathy, which releases ultra large von Willebrand factor (ULVWF) multimers from ECs and promotes ULVWF path of hemostasis. In the venous system, the activated ULVWF path initiates microthrombogenesis to form platelet-ULVWF complexes, which become "microthrombi strings" that produce venous endotheliopathy-associated vascular microthrombotic disease (vEA-VMTD) and immune thrombocytopenic purpura (ITP)-like syndrome. In the arterial system, endotheliopathy produces arterial EA-VMTD (aEA-VMTD) with "life-threatening" thrombotic thrombocytopenic purpura (TTP)-like syndrome. Typically, vEA-VMTD is "silent" unless complicated by additional local venous vascular injury. A local venous vessel trauma without sepsis produces localized macrothrombosis due to activated ULVWF and tissue factor (TF) paths from damaged ECs and SET, which causes distal DVT with good prognosis. However, if a septic patient with "silent" vEA-VMTD is complicated by additional vascular injury from in-hospital vascular accesses, "venous combined micro-macrothrombosis" may develop as VTE via the unifying mechanism of the "two-path unifying theory" of hemostasis. This paradigm shifting pathogenetic difference between distal DVT and proximal/central DVT calls for a reassessment of current therapeutic approaches.
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Affiliation(s)
- Jae C Chang
- Department of Medicine, Irvine School of Medicine, University of California, Irvine, CA 92868, USA
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De Michele L, Pierucci P, Giovannetti G, De Ceglie M, Dimitri M, Mirabile A, Quaranta V, Scardapane A, D'Agostino C, Carpagnano GE. Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up. Monaldi Arch Chest Dis 2022; 92. [PMID: 35044135 DOI: 10.4081/monaldi.2022.2142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 12/16/2021] [Indexed: 11/23/2022] Open
Abstract
The correct type and time of follow-up for patients affected by COVID19 ARDS is still unclear. The aim of this study was to evaluate at the survivors to COVID19 ARDS requiring non-invasive respiratory support (NRS) admitted to a Respiratory Intensive care unit (RICU) from March 8th till May 31th 2020 looking at all sequelae via a comprehensive follow up. All patients underwent a multi-disciplinary instrumental and clinical assessment within three months form admission to evaluate all infection related sequelae. Thirty-eight patients were enrolled Lung-Ultrasound (LUS) showed an outstanding discrimination ability (ROC AUC: 0.95) and a substantial agreement rate (Cohen's K: 0.74) compared to chest CT-scan detecting improvement of lung consolidations. Youden's test showed a cut-off pressure of 11 cmH2O ExpiratoryPAP-Continuous-PAP-max (EPAP-CPAP) applied at the airways during hospitalization to be significantly correlated (p value: 0.026) to the increased pulmonary artery common trunk diameter. A total of 8/38 patients (21.8%), 2 of whom during follow-up, were diagnosed with Pulmonary Emboli (PE) and started anticoagulant treatment. Patients with PE had a statistically significant shorter length of time of hospitalization, time to negative swab, CPAP/NIV duration, P/F ratio and D-dimers at follow-up compared to non PE. A comprehensive approach to patients with ARDS COVID19 requiring NRS is necessary. This study highlighted cardiopulmonary impairment related to the ARDS and to the high-EPAP-CPAP-max greater than 11mmHg provided during admission, the usefulness of LUS in monitoring post-infection recovery and the correct identification and treatment of patients with PE during follow up.
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Affiliation(s)
- Lucrezia De Michele
- Cardio Thoracic and Vascular Department, University Hospital Policlinic of Bari.
| | - Paola Pierucci
- Cardiothoracic Department, Respiratory and Critical Care Unit, Bari Policlinic University Hospital, Bari; Section of Respiratory Diseases, Department of Basic Medical Science Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari.
| | - Guido Giovannetti
- Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro' Medical School, Bari .
| | - Michele De Ceglie
- DIM, Interdisciplinary Department of Medicine, Section of Diagnostic Imaging, University of Bari 'Aldo Moro' Medical School, Bari .
| | - Michela Dimitri
- Section of Respiratory Diseases, Department of Basic Medical Science Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari.
| | - Alessandra Mirabile
- DIM, Interdisciplinary Department of Medicine, Section of Diagnostic Imaging, University of Bari 'Aldo Moro' Medical School, Bari .
| | | | - Arnaldo Scardapane
- DIM, Interdisciplinary Department of Medicine, Section of Diagnostic Imaging, University of Bari 'Aldo Moro' Medical School, Bari.
| | - Carlo D'Agostino
- DIM, Interdisciplinary Department of Medicine, Section of Diagnostic Imaging, University of Bari 'Aldo Moro' Medical School, Bari.
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Satoh T, Trudler D, Oh CK, Lipton SA. Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome. Antioxidants (Basel) 2022; 11:124. [PMID: 35052628 PMCID: PMC8772720 DOI: 10.3390/antiox11010124] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/27/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer's disease (AD), Parkinson's disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed "long-COVID." One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and "brain fog" are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood-brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.
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Affiliation(s)
- Takumi Satoh
- Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan
| | - Dorit Trudler
- Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (C.-K.O.)
| | - Chang-Ki Oh
- Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (C.-K.O.)
| | - Stuart A. Lipton
- Departments of Molecular Medicine and Neuroscience and Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA 92037, USA; (D.T.); (C.-K.O.)
- Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
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