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Janevska M, Naessens E, Verhasselt B. Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response. Viruses 2025; 17:569. [PMID: 40285011 PMCID: PMC12031613 DOI: 10.3390/v17040569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2025] [Revised: 04/08/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
SARS-CoV-2 has demonstrated a remarkable capacity for immune evasion. While initial studies focused on the Wuhan variant and adaptive immunity, later emerging strains such as Omicron exhibit mutations that may alter their immune-modulatory properties. We performed a comprehensive review of immune evasion mechanisms associated with SARS-CoV-2 viral proteins to focus on the evolutionary dynamics of immune modulation. We systematically analyzed and compared the impact of all currently known Wuhan and Omicron SARS-CoV-2 proteins on type I interferon (IFN) responses using a dual-luciferase reporter assay carrying an interferon-inducible promoter. Results revealed that Nsp1, Nsp5, Nsp14, and ORF6 are potent type I IFN inhibitors conserved across Wuhan and Omicron strains. Notably, we identified strain-specific differences, with Nsp6 and Spike proteins exhibiting enhanced IFN suppression in Omicron, whereas the Envelope protein largely retained this function. To extend these findings, we investigated selected proteins in primary human endothelial cells and also observed strain-specific differences in immune response with higher type I IFN response in cells expressing the Wuhan strain variant, suggesting that Omicron's adaptational mutations may contribute to a damped type I IFN response in the course of the pandemic's trajectory.
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Affiliation(s)
- Marija Janevska
- Department of Diagnostic Sciences, Ghent University, B9000 Ghent, Belgium;
| | - Evelien Naessens
- Department of Laboratory Medicine, Ghent University Hospital, B9000 Ghent, Belgium;
| | - Bruno Verhasselt
- Department of Diagnostic Sciences, Ghent University, B9000 Ghent, Belgium;
- Department of Laboratory Medicine, Ghent University Hospital, B9000 Ghent, Belgium;
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Yuan J, Wu D, Ye J, Chen R, Wang X, Zhang L. sFlt-1, Coagulation Function, and Platelets as Predictors of Preeclampsia. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2025; 47:102772. [PMID: 39884357 DOI: 10.1016/j.jogc.2025.102772] [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: 10/15/2024] [Revised: 01/05/2025] [Accepted: 01/08/2025] [Indexed: 02/01/2025]
Abstract
OBJECTIVE To investigate the predictive value of soluble FMS-like tyrosine kinase-1 (sFlt-1), coagulation function, and platelet (PLT) parameters for preeclampsia (PE). METHODS A prospective study was conducted on women registered and delivered at Shanghai Fifth People's Hospital from October 2020 to December 2021. All eligible pregnant women were recruited at the time of initial registration in the first trimester. We then obtained serum samples uniformly at 240-280 weeks and stored these samples in a freezer at -80°C and labelled them to create a biobank. Later, when PE was diagnosed, we followed the markers to find their blood samples and complete the tests. Participants were divided into healthy pregnant (HP) and PE groups. Participants were divided into HP and PE groups. Approximately 5 mL of venous blood was collected from each participant at 240-280 weeks gestation. Serum sFlt-1 was measured by enzyme-linked immunosorbent assay. Additionally, D-dimer, activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), antithrombin III (ATIII), fibrinogen, PLT, PLT distribution width (PDW), and mean PLT volume (MPV) were recorded. SPSS 27.0 software was used to analyze the correlation of these parameters with PE. Receiver operating characteristic curve analysis determined the optimal cutoff value for each parameter. RESULTS Serum sFlt-1, APTT, TT, ATIII, PLT, MPV, and PDW levels were significantly different between the PE and HP groups (P < 0.05). Among single-factor indicators for predicting PE, sFlt-1 exhibited the highest value. With an optimal cutoff value of 4.409 ng/mL, sFlt-1 demonstrated a sensitivity and specificity of 85.4% and 87.5%, respectively. The combination of sFlt-1, APTT, TT, PDW, and MPV yielded the highest predictive value, with an area under the receiver operating characteristic curve of 0.946, sensitivity of 86.8%, and specificity of 87.5%. CONCLUSIONS This study demonstrates that a combination of sFlt-1, APTT, TT, PDW, and MPV is a valuable tool for predicting PE.
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Affiliation(s)
- Jiani Yuan
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Duanqing Wu
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Jun Ye
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Rujun Chen
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Xiaoqin Wang
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
| | - Liwen Zhang
- Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
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Ammara M, Samiry I, Zaid Y, Oudghiri M, Naya A. A Pilot Study on the Role of TRAFs in the Development of SARS-CoV-2 Infection Before and After Immunization with AstraZeneca Chadox1 in Mice. Curr Issues Mol Biol 2025; 47:165. [PMID: 40136419 PMCID: PMC11941553 DOI: 10.3390/cimb47030165] [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: 01/08/2025] [Revised: 02/21/2025] [Accepted: 02/25/2025] [Indexed: 03/27/2025] Open
Abstract
The TRAF family of molecules are intracellular signaling adaptors that regulate various signaling pathways. These pathways are not only mediated by the TNFR superfamily and the Toll-like receptor/IL-1 receptor superfamily but also by unconventional cytokine receptors like IL-6 and IL-17 receptors. Overactive immune responses caused by TRAF signaling following the activation of these receptors frequently result in inflammatory and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and autoinflammatory syndromes. Therefore, it is crucial to comprehend the signaling processes controlled by TRAFs, which have a significant influence on the determination of cell fate (life or death) and the functioning, specialization, and endurance of cells in the innate and adaptive immune systems. Our data indicate that the dysregulation of cellular expression and/or signaling of TRAFs leads to the excessive production of pro-inflammatory cytokines, hence promoting abnormal activation of immune cells. The objective of our investigation was to comprehend the function of these molecules in SARS-CoV-2 infection both prior to and during SARS-CoV-2 vaccination. Our results demonstrate a clear inactivation of the TRAF5 and TRAF6 genes when infection occurs after immunization, in contrast to infection without prior vaccination. This can bolster the belief that immunization is essential while also demonstrating the involvement of these molecules in the pathogenesis of SARS-CoV-2.
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Affiliation(s)
- Mounia Ammara
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca 20000, Morocco; (M.A.); (I.S.); (Y.Z.); (M.O.)
| | - Inass Samiry
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca 20000, Morocco; (M.A.); (I.S.); (Y.Z.); (M.O.)
| | - Younes Zaid
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca 20000, Morocco; (M.A.); (I.S.); (Y.Z.); (M.O.)
- Materials, Nanotechnologies and Environment Laboratory, Department of Biology, Faculty of Sciences, Mohammed V University, Rabat 10000, Morocco
| | - Mounia Oudghiri
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca 20000, Morocco; (M.A.); (I.S.); (Y.Z.); (M.O.)
| | - Abdallah Naya
- Immunology and Biodiversity Laboratory, Department of Biology, Faculty of Sciences Ain Chock, Hassan II University, Casablanca 20000, Morocco; (M.A.); (I.S.); (Y.Z.); (M.O.)
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Wu M, Yan Y, Xie X, Bai J, Ma C, Du X. Effect of endothelial responses on sepsis-associated organ dysfunction. Chin Med J (Engl) 2024; 137:2782-2792. [PMID: 39501810 DOI: 10.1097/cm9.0000000000003342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Indexed: 12/17/2024] Open
Abstract
ABSTRACT Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.
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Affiliation(s)
- Miao Wu
- Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Yan Yan
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Xinyu Xie
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Jiawei Bai
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Chengtai Ma
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
| | - Xianjin Du
- Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
- Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
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Wang C, Wang S, Ma X, Yao X, Zhan K, Wang Z, He D, Zuo W, Han S, Zhao G, Cao B, Zhao J, Bian X, Wang J. P-selectin Facilitates SARS-CoV-2 Spike 1 Subunit Attachment to Vesicular Endothelium and Platelets. ACS Infect Dis 2024; 10:2656-2667. [PMID: 38912949 DOI: 10.1021/acsinfecdis.3c00728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/25/2024]
Abstract
SARS-CoV-2 infection starts from the association of its spike 1 (S1) subunit with sensitive cells. Vesicular endothelial cells and platelets are among the cell types that bind SARS-CoV-2, but the effectors that mediate viral attachment on the cell membrane have not been fully elucidated. Herein, we show that P-selectin (SELP), a biomarker for endothelial dysfunction and platelet activation, can facilitate the attachment of SARS-CoV-2 S1. Since we observe colocalization of SELP with S1 in the lung tissues of COVID-19 patients, we perform molecular biology experiments on human umbilical vein endothelial cells (HUVECs) to confirm the intermolecular interaction between SELP and S1. SELP overexpression increases S1 recruitment to HUVECs and enhances SARS-CoV-2 spike pseudovirion infection. The opposite results are determined after SELP downregulation. As S1 causes endothelial inflammatory responses in a dose-dependent manner, by activating the interleukin (IL)-17 signaling pathway, SELP-induced S1 recruitment may contribute to the development of a "cytokine storm" after viral infection. Furthermore, SELP also promotes the attachment of S1 to the platelet membrane. Employment of PSI-697, a small inhibitor of SELP, markedly decreases S1 adhesion to both HUVECs and platelets. In addition to the role of membrane SELP in facilitating S1 attachment, we also discover that soluble SELP is a prognostic factor for severe COVID-19 through a meta-analysis. In this study, we identify SELP as an adhesive site for the SARS-CoV-2 S1, thus providing a potential drug target for COVID-19 treatment.
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Affiliation(s)
- Cheng Wang
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Shaobo Wang
- Department of Nephrology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Xiangyu Ma
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Xiaohong Yao
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Kegang Zhan
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Zai Wang
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
| | - Di He
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100069, China
| | - Wenting Zuo
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Songling Han
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Gaomei Zhao
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Bin Cao
- National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100069, China
- China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China
- Changping Laboratory, Beijing 102206, China
- New Cornerstone Science Laboratory, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jinghong Zhao
- Department of Nephrology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Xiuwu Bian
- Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Junping Wang
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury of PLA, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China
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Shao HH, Yin RX. Pathogenic mechanisms of cardiovascular damage in COVID-19. Mol Med 2024; 30:92. [PMID: 38898389 PMCID: PMC11186295 DOI: 10.1186/s10020-024-00855-2] [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: 03/09/2024] [Accepted: 06/07/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.
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Affiliation(s)
- Hong-Hua Shao
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China
| | - Rui-Xing Yin
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China.
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
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van der Mescht MA, Steel HC, de Beer Z, Abdullah F, Ueckermann V, Anderson R, Rossouw TM. Comparison of platelet-and endothelial-associated biomarkers of disease activity in people hospitalized with Covid-19 with and without HIV co-infection. Front Immunol 2023; 14:1235914. [PMID: 37646024 PMCID: PMC10461055 DOI: 10.3389/fimmu.2023.1235914] [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: 06/06/2023] [Accepted: 07/24/2023] [Indexed: 09/01/2023] Open
Abstract
Introduction SARS-CoV-2 elicits a hyper-inflammatory response that contributes to increased morbidity and mortality in patients with COVID-19. In the case of HIV infection, despite effective anti-retroviral therapy, people living with HIV (PLWH) experience chronic systemic immune activation, which renders them particularly vulnerable to the life-threatening pulmonary, cardiovascular and other complications of SARS-CoV-2 co-infection. The focus of the study was a comparison of the concentrations of systemic indicators o\f innate immune dysfunction in SARS-CoV-2-PCR-positive patients (n=174) admitted with COVID-19, 37 of whom were co-infected with HIV. Methods Participants were recruited from May 2020 to November 2021. Biomarkers included platelet-associated cytokines, chemokines, and growth factors (IL-1β, IL-6, IL-8, MIP-1α, RANTES, PDGF-BB, TGF-β1 and TNF-α) and endothelial associated markers (IL-1β, IL-1Ra, ICAM-1 and VEGF). Results PLWH were significantly younger (p=0.002) and more likely to be female (p=0.001); median CD4+ T-cell count was 256 (IQR 115 -388) cells/μL and the median HIV viral load (VL) was 20 (IQR 20 -12,980) copies/mL. Fractional inspired oxygen (FiO2) was high in both groups, but higher in patients without HIV infection (p=0.0165), reflecting a greater need for oxygen supplementation. With the exception of PDGF-BB, the levels of all the biomarkers of innate immune activation were increased in SARS-CoV-2/HIV-co-infected and SARS-CoV-2/HIV-uninfected sub-groups relative to those of a control group of healthy participants. The magnitudes of the increases in the levels of these biomarkers were comparable between the SARS-CoV-2 -infected sub-groups, the one exception being RANTES, which was significantly higher in the sub-group without HIV. After adjusting for age, sex, and diabetes in the multivariable model, only the association between HIV status and VEGF was statistically significant (p=0.034). VEGF was significantly higher in PLWH with a CD4+ T-cell count >200 cells/μL (p=0.040) and those with a suppressed VL (p=0.0077). Discussion These findings suggest that HIV co-infection is not associated with increased intensity of the systemic innate inflammatory response during SARS-CoV-2 co-infection, which may underpin the equivalent durations of hospital stay, outcome and mortality rates in the SARS-CoV-2/HIV-infected and -uninfected sub-groups investigated in the current study. The apparent association of increased levels of plasma VEGF with SARS-CoV-2/HIV co-infection does, however, merit further investigation.
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Affiliation(s)
- Mieke A. van der Mescht
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Helen C. Steel
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Zelda de Beer
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Department of Family Medicine, Tshwane District Hospital, Pretoria, South Africa
| | - Fareed Abdullah
- Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria, South Africa
- Office of AIDS and TB Research, South African Medical Research Council, Pretoria, South Africa
| | - Veronica Ueckermann
- Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria, South Africa
| | - Ronald Anderson
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Theresa M. Rossouw
- Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Department of Family Medicine, Tshwane District Hospital, Pretoria, South Africa
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Zhao Y, Han X, Li C, Liu Y, Cheng J, Adhikari BK, Wang Y. COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability. Front Microbiol 2023; 14:1213111. [PMID: 37350790 PMCID: PMC10282193 DOI: 10.3389/fmicb.2023.1213111] [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: 04/27/2023] [Accepted: 05/18/2023] [Indexed: 06/24/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, of which cardiovascular system diseases are one of the main manifestations, such as myocarditis, myocardial infarction, and arrhythmia, which threaten the infected population worldwide. These diseases threaten the cardiovascular health of infected populations worldwide. Although the prevalence of coronavirus disease 2019 (COVID-19) has slightly improved with virus mutation and population vaccination, chronic infection, post-infection sequelae, and post-infection severe disease patients still exist, and it is still relevant to study the mechanisms linking COVID-19 to cardiovascular disease (CVD). This article introduces the pathophysiological mechanism of COVID-19-mediated cardiovascular disease and analyzes the mechanism and recent progress of the interaction between SARS-CoV-2 and the cardiovascular system from the roles of angiotensin-converting enzyme 2 (ACE2), cellular and molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, and psychosocial factors, respectively. We also discussed the differences and mechanisms involved in cardiovascular system diseases combined with neocoronavirus infection in different populations and provided a theoretical basis for better disease prevention and management.
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Affiliation(s)
- Yifan Zhao
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
| | - Xiaorong Han
- Department of Special Care Center, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Cheng Li
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
| | - Yucheng Liu
- Department of Family and Community Medicine, Feinberg School of Medicine, McGaw Medical Center of Northwestern University, Chicago, IL, United States
| | - Jiayu Cheng
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
| | | | - Yonggang Wang
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
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Adetunji JA, Fasae KD, Awe AI, Paimo OK, Adegoke AM, Akintunde JK, Sekhoacha MP. The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases. Heliyon 2023; 9:e17166. [PMID: 37484296 PMCID: PMC10361329 DOI: 10.1016/j.heliyon.2023.e17166] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/06/2023] [Accepted: 06/08/2023] [Indexed: 07/25/2023] Open
Abstract
The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.
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Affiliation(s)
- Joy A. Adetunji
- Nutritional and Industrial Biochemistry Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria
| | - Kehinde D. Fasae
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, USA
| | - Ayobami I. Awe
- Department of Biology, The Catholic University of America, Washington DC, USA
| | - Oluwatomiwa K. Paimo
- Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Ayodeji M. Adegoke
- Department of Pharmacology, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa
- Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, 200005, Nigeria
| | - Jacob K. Akintunde
- Department of Biochemistry, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Mamello P. Sekhoacha
- Department of Pharmacology, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa
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Vassiliou AG, Vrettou CS, Keskinidou C, Dimopoulou I, Kotanidou A, Orfanos SE. Endotheliopathy in Acute COVID-19 and Long COVID. Int J Mol Sci 2023; 24:8237. [PMID: 37175942 PMCID: PMC10179170 DOI: 10.3390/ijms24098237] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 04/28/2023] [Accepted: 04/30/2023] [Indexed: 05/15/2023] Open
Abstract
The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.
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Affiliation(s)
- Alice G. Vassiliou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 106 76 Athens, Greece; (C.S.V.); (C.K.); (I.D.); (A.K.)
| | | | | | | | | | - Stylianos E. Orfanos
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, 106 76 Athens, Greece; (C.S.V.); (C.K.); (I.D.); (A.K.)
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11
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Wadowski PP, Piechota-Polańczyk A, Andreas M, Kopp CW. Cardiovascular Disease Management in the Context of Global Crisis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 20:689. [PMID: 36613012 PMCID: PMC9819164 DOI: 10.3390/ijerph20010689] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 12/28/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) initiated a pandemic that has deteriorated health care access and thus disadvantaged vulnerable populations [...].
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Affiliation(s)
- Patricia P. Wadowski
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
| | - Aleksandra Piechota-Polańczyk
- Department of Medical Biotechnology, Faculty of Biophysics, Biochemistry and Biotechnology, Jagiellonian University, 30-387 Cracow, Poland
| | - Martin Andreas
- Department of Cardiac Surgery, Medical University of Vienna, 1090 Vienna, Austria
| | - Christoph W. Kopp
- Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
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12
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Aleksova A, Fluca AL, Gagno G, Pierri A, Padoan L, Derin A, Moretti R, Noveska EA, Azzalini E, D'Errico S, Beltrami AP, Zumla A, Ippolito G, Sinagra G, Janjusevic M. Long-term effect of SARS-CoV-2 infection on cardiovascular outcomes and all-cause mortality. Life Sci 2022; 310:121018. [PMID: 36183780 PMCID: PMC9561478 DOI: 10.1016/j.lfs.2022.121018] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/19/2022] [Accepted: 09/27/2022] [Indexed: 12/03/2022]
Abstract
Since the very beginning of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, it was evident that patients with cardiovascular disease (CVD) were at an increased risk of developing severe illness, and complications spanning cerebrovascular disorders, dysrhythmias, acute coronary syndrome, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, thromboembolic disease, stroke, and death. Underlying these was excessive systemic inflammation and coagulopathy due to SARS-COV-2 infection, the effects of which also continued long-term as evidenced by post-COVID-19 cardiovascular complications. The acute and chronic cardiovascular effects of COVID-19 occurred even among those who were not hospitalized and had no previous CVD or those with mild symptoms. This comprehensive review summarizes the current understanding of molecular mechanisms triggered by the SARS-CoV-2 virus on various cells that express the angiotensin-converting enzyme 2, leading to endothelial dysfunction, inflammation, myocarditis, impaired coagulation, myocardial infarction, arrhythmia and a multisystem inflammatory syndrome in children or Kawasaki-like disease.
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Affiliation(s)
- Aneta Aleksova
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy.
| | - Alessandra Lucia Fluca
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Giulia Gagno
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Alessandro Pierri
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Laura Padoan
- Department of Cardiology and Cardiovascular Physiopathology, Università degli Studi di Perugia, Perugia, Italy
| | - Agnese Derin
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy
| | - Rita Moretti
- Department of Internal Medicine and Neurology, Neurological Clinic, University of Trieste, Trieste, Italy
| | - Elena Aleksova Noveska
- Department of Pediatric and Preventive Dentistry, Faculty of Dental Medicine, Ss. Cyril and Methodius University, Skopje, Macedonia
| | - Eros Azzalini
- Department of Medical Sciences (DSM), University of Trieste, Trieste, Italy
| | - Stefano D'Errico
- Department of Medicine, Surgery and Health, University of Trieste, Trieste, Italy
| | | | - Alimuddin Zumla
- Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK; National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK
| | | | - Gianfranco Sinagra
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Milijana Janjusevic
- Azienda Sanitaria Universitaria Giuliano Isontina, Cardiothoracovascular Department, Trieste, Italy; Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
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Falcinelli E, Petito E, Gresele P. The role of platelets, neutrophils and endothelium in COVID-19 infection. Expert Rev Hematol 2022; 15:727-745. [PMID: 35930267 DOI: 10.1080/17474086.2022.2110061] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION COVID-19 is associated to an increased risk of thrombosis, as a result of a complex process that involves the activation of vascular and circulating cells, the release of soluble inflammatory and thrombotic mediators and blood clotting activation. AREAS COVERED This article reviews the pathophysiological role of platelets, neutrophils and the endothelium, and of their interactions, in the thrombotic complications of COVID-19 patients, and the current and future therapeutic approaches targeting these cell types. EXPERT OPINION Virus-induced platelet, neutrophil and endothelial cell changes are crucial triggers of the thrombotic complications and of the adverse evolution of COVID-19. Both the direct interaction with the virus and the associated cytokine storm concur to trigger cell activation in a classical thromboinflammatory vicious circle. Although heparin has proven to be an effective prophylactic and therapeutic weapon for the prevention and treatment of COVID-19-associated thrombosis, it acts downstream of the cascade of events triggered by SARS-CoV-2. The identification of specific molecular targets interrupting the thromboinflammatory cascade upstream, and more specifically acting either on the interaction of SARS-CoV-2 with blood and vascular cells or on the specific signalling mechanisms associated with their COVID-19-associated activation, might theoretically offer greater protection with potentially lesser side effects.
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Affiliation(s)
- E Falcinelli
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - E Petito
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - P Gresele
- Section of Internal and Cardiovascular Medicine, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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COVID-19 and Parkinsonism: A Critical Appraisal. Biomolecules 2022; 12:biom12070970. [PMID: 35883526 PMCID: PMC9313170 DOI: 10.3390/biom12070970] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 11/16/2022] Open
Abstract
A few cases of parkinsonism linked to COVID-19 infection have been reported so far, raising the possibility of a post-viral parkinsonian syndrome. The objective of this review is to summarize the clinical, biological, and neuroimaging features of published cases describing COVID-19-related parkinsonism and to discuss the possible pathophysiological mechanisms. A comprehensive literature search was performed using NCBI’s PubMed database and standardized search terms. Thirteen cases of COVID-19-related parkinsonism were included (7 males; mean age: 51 years ± 14.51, range 31–73). Patients were classified based on the possible mechanisms of post-COVID-19 parkinsonism: extensive inflammation or hypoxic brain injury within the context of encephalopathy (n = 5); unmasking of underlying still non-symptomatic Parkinson’s Disease (PD) (n = 5), and structural and functional basal ganglia damage (n = 3). The various clinical scenarios show different outcomes and responses to dopaminergic treatment. Different mechanisms may play a role, including vascular damage, neuroinflammation, SARS-CoV-2 neuroinvasive potential, and the impact of SARS-CoV-2 on α-synuclein. Our results confirm that the appearance of parkinsonism during or immediately after COVID-19 infection represents a very rare event. Future long-term observational studies are needed to evaluate the possible role of SARS-CoV-2 infection as a trigger for the development of PD in the long term.
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Batu ED, Sener S, Ozen S. COVID-19 associated pediatric vasculitis: A systematic review and detailed analysis of the pathogenesis. Semin Arthritis Rheum 2022; 55:152047. [PMID: 35709649 PMCID: PMC9183245 DOI: 10.1016/j.semarthrit.2022.152047] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/20/2022] [Accepted: 06/07/2022] [Indexed: 12/23/2022]
Abstract
Objectives Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, has opened a new era in the practice of pediatric rheumatology since it has been associated with inflammatory complications such as vasculitis and arthritis. In this review, we aimed to present a detailed analysis of COVID-19 associated pediatric vasculitis. Methods A systematic review of the English literature was performed through Pubmed/MEDLINE and Scopus up to January 1st, 2022. Articles including data about the patients with 1) onset of vasculitis <18 years of age, 2) evidence of SARS-CoV-2 exposure, 3) evidence of vasculitis diagnosis (imaging, histopathologic evidences or fulfilling the specific diagnostic/classification criteria) were included in the final analysis. Patients with Kawasaki disease-like vasculitis associated with multisystem inflammatory syndrome in children (MIS-C) were excluded. Results A total of 25 articles describing 36 patients with COVID-19 associated pediatric vasculitis (median age 13 years; M/F: 2.3) were included. The most frequent phenotype was IgA vasculitis (n=9) followed by chilblains (n=7) and ANCA associated vasculitis (AAV) (n=5). Skin (58.3%) and renal (30.5%) involvements were the most common manifestations of vasculitis. The majority of patients received corticosteroids (40%), while rituximab (14.2%) and cyclophosphamide (11.4%) were the most frequently used immunosuppressive drugs. Remission was achieved in 23 of 28 patients. Five patients (4 with central nervous system vasculitis; 1 with AAV) died. Conclusion Although COVID-19 associated pediatric vasculitis is very rare, awareness of this rare entity is important to secure earlier diagnosis and treatment. The clinical features of COVID-19 associated pediatric vasculitis subtypes look similar to those in pediatric vasculitis not associated with COVID-19. Whether COVID-19 is the reason of the vasculitis or only the trigger remains unknown.
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Affiliation(s)
- Ezgi Deniz Batu
- Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Rheumatology, Ankara, Turkey.
| | - Seher Sener
- Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Rheumatology, Ankara, Turkey
| | - Seza Ozen
- Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Rheumatology, Ankara, Turkey
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