{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:15:07Z","timestamp":1773332107297,"version":"3.50.1"},"reference-count":205,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL071837"],"award-info":[{"award-number":["HL071837"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL153270"],"award-info":[{"award-number":["HL153270"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM083016"],"award-info":[{"award-number":["GM083016"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM119197"],"award-info":[{"award-number":["GM119197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006514","name":"East Tennessee State University","doi-asserted-by":"publisher","award":["C06RR0306551"],"award-info":[{"award-number":["C06RR0306551"]}],"id":[{"id":"10.13039\/100006514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["916710"],"award-info":[{"award-number":["916710"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.<\/jats:p>","DOI":"10.3389\/fimmu.2022.868679","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T21:56:34Z","timestamp":1648504594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate"],"prefix":"10.3389","volume":"13","author":[{"given":"Kun","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Holt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuanzhu","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanfu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-020-00671-y","article-title":"Emerging Treatment Strategies for COVID-19 Infection","volume":"21","author":"Gavriatopoulou","year":"2021","journal-title":"Clin Exp Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25829","article-title":"Hematological Findings and Complications of COVID-19","volume":"95","author":"Terpos","year":"2020","journal-title":"Am J Hematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27487","article-title":"COVID-19 Vaccinations: The Unknowns, Challenges, and Hopes","volume":"94","author":"Mohamed","year":"2022","journal-title":"J Med Virol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40495-020-00239-0","article-title":"The Case Fatality Rate in COVID-19 Patients With Cardiovascular Disease: Global Health Challenge and Paradigm in the Current Pandemic","author":"Dan","year":"2020","journal-title":"Curr Pharmacol Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0413-9","article-title":"COVID-19 and Cardiovascular Disease: From Basic Mechanisms to Clinical Perspectives","author":"Nishiga","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2020.03.013","article-title":"Cardiovascular Disease and COVID-19","volume":"14","author":"Bansal","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2020.06.026","article-title":"COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors","volume":"17","author":"Mitrani","year":"2020","journal-title":"Heart Rhythm"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial Cell Infection and Endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"110320","DOI":"10.1016\/j.mehy.2020.110320","article-title":"SARS-CoV-2 Cell Entry Receptor ACE2 Mediated Endothelial Dysfunction Leads to Vascular Thrombosis in COVID-19 Patients","volume":"145","author":"Kumar","year":"2020","journal-title":"Med Hypotheses"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.587913","article-title":"Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-kappaB Activation via GPR81-Mediated Signaling","volume":"11","author":"Yang","year":"2020","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00841-9","article-title":"Lactate Promotes Macrophage HMGB1 Lactylation, Acetylation, and Exosomal Release in Polymicrobial Sepsis","volume":"29","author":"Yang","year":"2021","journal-title":"Cell Death Differ"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3547","DOI":"10.1038\/s41467-020-17402-2","article-title":"Lactate Released by Inflammatory Bone Marrow Neutrophils Induces Their Mobilization via Endothelial GPR81 Signaling","volume":"11","author":"Khatib-Massalha","year":"2020","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.06.004","article-title":"Itaconate Links Inhibition of Succinate Dehydrogenase With Macrophage Metabolic Remodeling and Regulation of Inflammation","volume":"24","author":"Lampropoulou","year":"2016","journal-title":"Cell Metab"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1161\/ATVBAHA.120.314037","article-title":"Metabolic Reprogramming in Immune Response and Tissue Inflammation","volume":"40","author":"Sun","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.11.010","article-title":"The Key Role of Warburg Effect in SARS-CoV-2 Replication and Associated Inflammatory Response","volume":"180","author":"Icard","year":"2021","journal-title":"Biochimie"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.302855","article-title":"Endothelial Cell Metabolism in Normal and Diseased Vasculature","volume":"116","author":"Eelen","year":"2015","journal-title":"Circ Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nri2802","article-title":"Immunity and Immunopathology to Viruses: What Decides the Outcome","volume":"10","author":"Rouse","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.038","article-title":"Viral Activation of Cellular Metabolism","author":"Sanchez","year":"2015","journal-title":"Virology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.cell.2019.05.003","article-title":"Lactate Is a Natural Suppressor of RLR Signaling by Targeting MAVS","volume":"178","author":"Zhang","year":"2019","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00227","article-title":"Aerobic Glycolysis: Beyond Proliferation","volume":"6","author":"Jones","year":"2015","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0243-4","article-title":"Lactate: The Ugly Duckling of Energy Metabolism","volume":"2","author":"Rabinowitz","year":"2020","journal-title":"Nat Metab"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama-Journal Am Med Assoc"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v7.i8.483","article-title":"Clinical Significance of Lactate in Acute Cardiac Patients","volume":"7","author":"Lazzeri","year":"2015","journal-title":"World J Cardiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1156","article-title":"Increased Blood Lactate is Prevalent and Identifies Poor Prognosis in Patients With Acute Heart Failure Without Overt Peripheral Hypoperfusion","volume":"20","author":"Zymlinski","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00231","article-title":"Lactate Beyond a Waste Metabolite: Metabolic Affairs and Signaling in Malignancy","volume":"10","author":"Baltazar","year":"2020","journal-title":"Front Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1186\/s13054-020-03161-5","article-title":"Lactate Dehydrogenase Elevations is Associated With Severity of COVID-19: A Meta-Analysis","volume":"24","author":"Chen","year":"2020","journal-title":"Crit Care"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.04.006","article-title":"Risk Factors for Severity and Mortality in Adult COVID-19 Inpatients in Wuhan","volume":"146","author":"Li","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12931-020-01427-8","article-title":"Clinical Evaluation of Potential Usefulness of Serum Lactate Dehydrogenase (LDH) in 2019 Novel Coronavirus (COVID-19) Pneumonia","volume":"21","author":"Wu","year":"2020","journal-title":"Respir Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103372","article-title":"Lactate Dehydrogenase, an Independent Risk Factor of Severe COVID-19 Patients: A Retrospective and Observational Study","volume":"12","author":"Han","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/metabo10100386","article-title":"Lactate Kinetics Reflect Organ Dysfunction and Are Associated With Adverse Outcomes in Intensive Care Unit Patients With COVID-19 Pneumonia: Preliminary Results From a GREEK Single-Centre Study","volume":"10","author":"Vassiliou","year":"2020","journal-title":"Metabolites"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.20-1282","article-title":"Longitudinal Monitoring of Lactate in Hospitalized and Ambulatory COVID-19 Patients","volume":"104","author":"Velavan","year":"2021","journal-title":"Am J Trop Med Hyg"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4743904","DOI":"10.1101\/2020.05.08.20095042","article-title":"Lactate Arterial-Central Venous Gradient Among COVID-19 Patients in ICU: A Potential Tool in the Clinical Practice","volume":"2020","author":"Nardi","year":"2020","journal-title":"Crit Care Res Pract"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1113\/EP089474","article-title":"The Role of Lactate in Sepsis and COVID-19: Perspective From Contracting Skeletal Muscle Metabolism","author":"Iepsen","year":"2021","journal-title":"Exp Physiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120236","article-title":"Metabolic Regulation of Immune Responses","volume":"32","author":"Ganeshan","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.012673","article-title":"Glucose Metabolism in Cardiac Hypertrophy and Heart Failure","volume":"8","author":"Tran","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.1286","article-title":"Potential Effects of Coronaviruses on the Cardiovascular System: A Review","volume":"5","author":"Madjid","year":"2020","journal-title":"JAMA Cardiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7","article-title":"A Pneumonia Outbreak Associated With a New Coronavirus of Probable Bat Origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/v12020244","article-title":"Systematic Comparison of Two Animal-To-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV","volume":"12","author":"Xu","year":"2020","journal-title":"Viruses"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4108","DOI":"10.1038\/s41598-021-83595-1","article-title":"Molecular Features Similarities Between SARS-CoV-2, SARS, MERS and Key Human Genes Could Favour the Viral Infections and Trigger Collateral Effects","volume":"11","author":"Maldonado","year":"2021","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"9110","DOI":"10.1038\/s41598-017-09536-z","article-title":"Altered Lipid Metabolism in Recovered SARS Patients Twelve Years After Infection","volume":"7","author":"Wu","year":"2017","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0243191","article-title":"Prevalence and Predictors of Death and Severe Disease in Patients Hospitalized Due to COVID-19: A Comprehensive Systematic Review and Meta-Analysis of 77 Studies and 38,000 Patients","volume":"15","author":"Dorjee","year":"2020","journal-title":"PloS One"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046941","article-title":"COVID-19 and Cardiovascular Disease","volume":"141","author":"Clerkin","year":"2020","journal-title":"Circulation"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.0950","article-title":"Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China","volume":"5","author":"Shi","year":"2020","journal-title":"JAMA Cardiol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4031","article-title":"Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy","volume":"323","author":"Grasselli","year":"2020","journal-title":"JAMA"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2010419","article-title":"Clinical Characteristics of Covid-19 in New York City","volume":"382","author":"Goyal","year":"2020","journal-title":"N Engl J Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2020.10.022","article-title":"Cardiovascular Diseases Burden in COVID-19: Systematic Review and Meta-Analysis","volume":"46","author":"Hessami","year":"2021","journal-title":"Am J Emerg Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-020-01626-9","article-title":"Prevalence and Impact of Cardiovascular Metabolic Diseases on COVID-19 in China","volume":"109","author":"Li","year":"2020","journal-title":"Clin Res Cardiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0360-5","article-title":"COVID-19 and the Cardiovascular System","volume":"17","author":"Zheng","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.carrev.2021.04.007","article-title":"Systemic Inflammation may Induce Cardiac Injury in COVID-19 Patients Including Children and Adolescents Without Underlying Cardiovascular Diseases: A Systematic Review","volume":"35","author":"Saed Aldien","year":"2021","journal-title":"Cardiovasc Revasc Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"155496","DOI":"10.1016\/j.cyto.2021.155496","article-title":"Glycyrrhizin Prevents SARS-CoV-2 S1 and Orf3a Induced High Mobility Group Box 1 (HMGB1) Release and Inhibits Viral Replication","volume":"142","author":"Gowda","year":"2021","journal-title":"Cytokine"},{"key":"B53","doi-asserted-by":"publisher","first-page":"100052","DOI":"10.1016\/j.xcrm.2020.100052","article-title":"Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection","volume":"1","author":"Sharma","year":"2020","journal-title":"Cell Rep Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2020.09.060","article-title":"Usefulness of Elevated Troponin to Predict Death in Patients With COVID-19 and Myocardial Injury","volume":"138","author":"Majure","year":"2021","journal-title":"Am J Cardiol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018477","article-title":"Troponin and Other Biomarker Levels and Outcomes Among Patients Hospitalized With COVID-19: Derivation and Validation of the HA2T2 COVID-19 Mortality Risk Score","volume":"10","author":"Manocha","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.3538","article-title":"Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019: Results of a Multicenter Study","volume":"5","author":"Lombardi","year":"2020","journal-title":"JAMA Cardiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.3551","article-title":"Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases","volume":"5","author":"Lindner","year":"2020","journal-title":"JAMA Cardiol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14768","article-title":"Abnormal Coagulation Parameters are Associated With Poor Prognosis in Patients With Novel Coronavirus Pneumonia","volume":"18","author":"Tang","year":"2020","journal-title":"J Thromb Haemost"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.04.013","article-title":"Incidence of Thrombotic Complications in Critically Ill ICU Patients With COVID-19","volume":"191","author":"Klok","year":"2020","journal-title":"Thromb Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15029","article-title":"Hypoxia - an Overlooked Trigger for Thrombosis in COVID-19 and Other Critically Ill Patients","volume":"18","author":"Thachil","year":"2020","journal-title":"J Thromb Haemost"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2020","article-title":"Inflammation and Thrombosis in COVID-19 Pathophysiology: Proteinase-Activated and Purinergic Receptors as Drivers and Candidate Therapeutic Targets","volume":"101","author":"Sriram","year":"2021","journal-title":"Physiol Rev"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14817","article-title":"Anticoagulant Treatment is Associated With Decreased Mortality in Severe Coronavirus Disease 2019 Patients With Coagulopathy","volume":"18","author":"Tang","year":"2020","journal-title":"J Thromb Haemost"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-020-00541-w","article-title":"Blood Pressure Control and Adverse Outcomes of COVID-19 Infection in Patients With Concomitant Hypertension in Wuhan, China","volume":"43","author":"Ran","year":"2020","journal-title":"Hypertens Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/nri2171","article-title":"Evolving Functions of Endothelial Cells in Inflammation","volume":"7","author":"Pober","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01568","article-title":"Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide","volume":"10","author":"Sun","year":"2019","journal-title":"Front Pharmacol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1186\/cc1864","article-title":"Bench-To-Bedside Review: Endothelial Cell Dysfunction in Severe Sepsis: A Role in Organ Dysfunction","volume":"7","author":"Vallet","year":"2003","journal-title":"Crit Care"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.687783","article-title":"SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity","volume":"8","author":"Raghavan","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253347","article-title":"SARS-CoV-2 Uses Major Endothelial Integrin Alphavbeta3 to Cause Vascular Dysregulation in-Vitro During COVID-19","volume":"16","author":"Nader","year":"2021","journal-title":"PloS One"},{"key":"B70","doi-asserted-by":"publisher","first-page":"2001634","DOI":"10.1183\/13993003.01634-2020","article-title":"Endothelial Cell Dysfunction: A Major Player in SARS-CoV-2 Infection (COVID-19)","volume":"56","author":"Huertas","year":"2020","journal-title":"Eur Respir J"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N Engl J Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1101\/2021.08.01.454605","article-title":"The Spike Protein of SARS-CoV-2 Induces Endothelial Inflammation Through Integrin \u03b15\u03b21 and NF-\u03baB","volume":"298","author":"Robles","year":"2021","journal-title":"bioRxiv"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.16.5912-5922.2002","article-title":"Alpha 5 Beta 1 Integrin Activates an NF-Kappa B-Dependent Program of Gene Expression Important for Angiogenesis and Inflammation","volume":"22","author":"Klein","year":"2002","journal-title":"Mol Cell Biol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e69314","DOI":"10.7554\/eLife.69314","article-title":"Effect of SARS-CoV-2 Proteins on Vascular Permeability","volume":"10","author":"Rauti","year":"2021","journal-title":"bioRxiv"},{"key":"B75","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41392-021-00747-5","article-title":"SARS-CoV-2 Leads to Myocardial Injury in Rhesus Macaque","volume":"6","author":"Feng","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20209610","article-title":"The Protein Expression Profile of ACE2 in Human Tissues","volume":"16","author":"Hikmet","year":"2020","journal-title":"Mol Syst Biol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.06.003","article-title":"Trilogy of ACE2: A Peptidase in the Renin-Angiotensin System, a SARS Receptor, and a Partner for Amino Acid Transporters","volume":"128","author":"Kuba","year":"2010","journal-title":"Pharmacol Ther"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002615200","article-title":"A Human Homolog of Angiotensin-Converting Enzyme. Cloning and Functional Expression as a Captopril-Insensitive Carboxypeptidase","volume":"275","author":"Tipnis","year":"2000","journal-title":"J Biol Chem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145","article-title":"Angiotensin-Converting Enzyme 2 is a Functional Receptor for the SARS Coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nm1267","article-title":"A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-Induced Lung Injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat Med"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570","article-title":"Tissue Distribution of ACE2 Protein, the Functional Receptor for SARS Coronavirus. A First Step in Understanding SARS Pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J Pathol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e61390","DOI":"10.7554\/eLife.61390","article-title":"ACE2: Evidence of Role as Entry Receptor for SARS-CoV-2 and Implications in Comorbidities","volume":"9","author":"Zamorano Cuervo","year":"2020","journal-title":"Elife"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003138117","article-title":"Cell Entry Mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B84","article-title":"The Vascular Endothelium: The Cornerstone of Organ Dysfunction in Severe SARS-CoV-2 Infection","volume-title":"Critical Care","author":"Pons","year":"2020"},{"key":"B85","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0343-0","article-title":"Covid-19: The Vasculature Unleashed","volume":"20","author":"Teuwen","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137244","article-title":"Clinical and Immunological Features of Severe and Moderate Coronavirus Disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J Clin Invest"},{"key":"B89","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.cell.2020.04.004","article-title":"Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human Ace2","volume":"181","author":"Monteil","year":"2020","journal-title":"Cell"},{"key":"B90","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12915-019-0678-9","article-title":"Viral Hijacking of Cellular Metabolism","volume":"17","author":"Thaker","year":"2019","journal-title":"BMC Biol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"e140327","DOI":"10.1172\/jci.insight.140327","article-title":"COVID-19 Infection Alters Kynurenine and Fatty Acid Metabolism, Correlating With IL-6 Levels and Renal Status","volume":"5","author":"Thomas","year":"2020","journal-title":"JCI Insight"},{"key":"B92","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cell.2020.05.032","article-title":"Proteomic and Metabolomic Characterization of COVID-19 Patient Sera","volume":"182","author":"Shen","year":"2020","journal-title":"Cell"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2020.06.016","article-title":"Metabolic Syndrome and COVID-19: An Update on the Associated Comorbidities and Proposed Therapies","volume":"14","author":"Costa","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3319","article-title":"Diabetes is a Risk Factor for the Progression and Prognosis of COVID-19","author":"Guo","year":"2020","journal-title":"Diabetes Metab Res Rev"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3606770","article-title":"Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response Through a HIF-1alpha\/Glycolysis-Dependent Axis","volume":"32","author":"Codo","year":"2020","journal-title":"Cell Metab"},{"key":"B96","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12890-021-01413-w","article-title":"Elevated Glucose Level Leads to Rapid COVID-19 Progression and High Fatality","volume":"21","author":"Wang","year":"2021","journal-title":"BMC Pulm Med"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02075","article-title":"The Metabolic Changes and Immune Profiles in Patients With COVID-19","volume":"11","author":"He","year":"2020","journal-title":"Front Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.07.027","article-title":"Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis","volume":"430","author":"Yu","year":"2018","journal-title":"J Mol Biol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.07.008","article-title":"The Evolving Role of Mitochondria in Metabolism","volume":"23","author":"Tzameli","year":"2012","journal-title":"Trends Endocrinol Metab"},{"key":"B100","doi-asserted-by":"publisher","first-page":"101631","DOI":"10.1016\/j.isci.2020.101631","article-title":"Mitochondria: In the Cross Fire of SARS-CoV-2 and Immunity","volume":"23","author":"Burtscher","year":"2020","journal-title":"iScience"},{"key":"B101","doi-asserted-by":"publisher","first-page":"105114","DOI":"10.1016\/j.micpath.2021.105114","article-title":"Host Metabolic Reprogramming in Response to SARS-CoV-2 Infection: A Systems Biology Approach","volume":"158","author":"Moolamalla","year":"2021","journal-title":"Microb Pathog"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.614650","article-title":"Impact of COVID-19 on Mitochondrial-Based Immunity in Aging and Age-Related Diseases","volume":"12","author":"Ganji","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B103","doi-asserted-by":"publisher","first-page":"41","DOI":"10.12703\/P7-41","article-title":"Chicken or the Egg: Warburg Effect and Mitochondrial Dysfunction","volume":"7","author":"Senyilmaz","year":"2015","journal-title":"F1000Prime Rep"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1113\/JP278810","article-title":"Revisiting the Warburg Effect: Historical Dogma Versus Current Understanding","volume":"599","author":"Vaupel","year":"2021","journal-title":"J Physiol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00426.2020","article-title":"Mitochondrial Metabolic Manipulation by SARS-CoV-2 in Peripheral Blood Mononuclear Cells of Patients With COVID-19","volume":"320","author":"Ajaz","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12950-020-00263-3","article-title":"Hypoxia: A Key Feature of COVID-19 Launching Activation of HIF-1 and Cytokine Storm","volume":"17","author":"Jahani","year":"2020","journal-title":"J\u00a0Inflamm (Lond)"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314515","article-title":"COVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions","volume":"40","author":"Brosnahan","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15327","article-title":"Glycolysis - a Key Player in the Inflammatory Response","volume":"287","author":"Soto-Heredero","year":"2020","journal-title":"FEBS J"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.602848","article-title":"Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19","volume":"12","author":"Olwal","year":"2021","journal-title":"Front Immunol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30920-X","article-title":"Sars-Cov-2 and Viral Sepsis: Observations and Hypotheses","volume":"395","author":"Li","year":"2020","journal-title":"Lancet"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050543","article-title":"Myocardial Injury in Severe COVID-19 Compared With Non-COVID-19 Acute Respiratory Distress Syndrome","volume":"143","author":"Metkus","year":"2021","journal-title":"Circulation"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2020.05.073","article-title":"Lactate Dehydrogenase Levels Predict Coronavirus Disease 2019 (COVID-19) Severity and Mortality: A Pooled Analysis","volume":"38","author":"Henry","year":"2020","journal-title":"Am J Emerg Med"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490","article-title":"Functional Polarization of Tumour-Associated Macrophages by Tumour-Derived Lactic Acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000958","article-title":"Lactate and Immunosuppression in Sepsis","volume":"49","author":"Nolt","year":"2018","journal-title":"Shock"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0688-7","article-title":"Lactate Modulates CD4(+) T-Cell Polarization and Induces an Immunosuppressive Environment, Which Sustains Prostate Carcinoma Progression via TLR8\/miR21 Axis","volume":"38","author":"Comito","year":"2019","journal-title":"Oncogene"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13800","article-title":"Lactate Administration Activates the ERK1\/2, Mtorc1, and AMPK Pathways Differentially According to Skeletal Muscle Type in Mouse","volume":"6","author":"Cerda-Kohler","year":"2018","journal-title":"Physiol Rep"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks066","article-title":"Lactate, a Product of Glycolytic Metabolism, Inhibits Histone Deacetylase Activity and Promotes Changes in Gene Expression","volume":"40","author":"Latham","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.8164","article-title":"Macrophage Transcriptome Modification Induced by Hypoxia and Lactate","volume":"18","author":"Zhao","year":"2019","journal-title":"Exp Ther Med"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic Regulation of Gene Expression by Histone Lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.2174\/1874192401004010302","article-title":"The Endothelium and its Role in Regulating Vascular Tone","volume":"4","author":"Sandoo","year":"2010","journal-title":"Open Cardiovasc Med J"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.701278","article-title":"SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro","volume":"11","author":"Liu","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3390\/v13010029","article-title":"Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19","volume":"13","author":"Bernard","year":"2020","journal-title":"Viruses"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049465","article-title":"Unexpected Features of Cardiac Pathology in COVID-19 Infection","volume":"142","author":"Fox","year":"2020","journal-title":"Circulation"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1971","article-title":"The Multifaceted Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification","volume":"6","author":"Bertolini","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"B125","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/rth2.12158","article-title":"Circulating Endothelial Cells as Biomarker for Cardiovascular Diseases","volume":"3","author":"Farinacci","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2014.1001999","article-title":"Clinical Significance of Circulating Endothelial Cells in Patients With Severe Sepsis or Septic Shock","volume":"47","author":"Yoo","year":"2015","journal-title":"Infect Dis (Lond)"},{"key":"B127","doi-asserted-by":"publisher","first-page":"e64909","DOI":"10.7554\/eLife.64909","article-title":"Convalescent COVID-19 Patients are Susceptible to Endothelial Dysfunction Due to Persistent Immune Activation","volume":"10","author":"Chioh","year":"2021","journal-title":"Elife"},{"key":"B128","doi-asserted-by":"publisher","first-page":"e72873","DOI":"10.7554\/eLife.72873","article-title":"HIF1alpha Stabilization in Hypoxia is Not Oxidant-Initiated","volume":"10","author":"Kumar","year":"2021","journal-title":"Elife"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.651656","article-title":"Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019","volume":"12","author":"Qi","year":"2021","journal-title":"Front Immunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00440-07","article-title":"Hypoxia-Inducible Factor 1 and Dysregulated C-Myc Cooperatively Induce Vascular Endothelial Growth Factor and Metabolic Switches Hexokinase 2 and Pyruvate Dehydrogenase Kinase 1","volume":"27","author":"Kim","year":"2007","journal-title":"Mol Cell Biol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1529107","article-title":"The Transcription Factor HIF-1alpha Plays a Critical Role in the Growth Factor-Dependent Regulation of Both Aerobic and Anaerobic Glycolysis","volume":"21","author":"Lum","year":"2007","journal-title":"Genes Dev"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046571","article-title":"Lactate Activates HIF-1 in Oxidative But Not in Warburg-Phenotype Human Tumor Cells","volume":"7","author":"De Saedeleer","year":"2012","journal-title":"PloS One"},{"key":"B133","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/s41392-021-00726-w","article-title":"HIF-1alpha Promotes SARS-CoV-2 Infection and Aggravates Inflammatory Responses to COVID-19","volume":"6","author":"Tian","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00274.2009","article-title":"Critical Role for Lactate Dehydrogenase A in Aerobic Glycolysis That Sustains Pulmonary Microvascular Endothelial Cell Proliferation","volume":"299","author":"Parra-Bonilla","year":"2010","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075984","article-title":"Lactate Dehydrogenase a Expression is Necessary to Sustain Rapid Angiogenesis of Pulmonary Microvascular Endothelium","volume":"8","author":"Parra-Bonilla","year":"2013","journal-title":"PloS One"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e328344b446","article-title":"Multiple Organ Failure in Sepsis: Prognosis and Role of Systemic Inflammatory Response","volume":"17","author":"Gustot","year":"2011","journal-title":"Curr Opin Crit Care"},{"key":"B137","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s13054-020-02995-3","article-title":"The Association of Low Serum Albumin Level With Severe COVID-19: A Systematic Review and Meta-Analysis","volume":"24","author":"Aziz","year":"2020","journal-title":"Crit Care"},{"key":"B138","first-page":"2020.05.17.20104877","article-title":"COVID-19: The Key Role of Pulmonary Capillary Leakage. An Observational Cohort Study","author":"Wu","year":"2020","journal-title":"medRxiv"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00519","article-title":"Mechanisms Ensuring Endothelial Junction Integrity Beyond VE-Cadherin","volume":"11","author":"Duong","year":"2020","journal-title":"Front Physiol"},{"key":"B140","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.bbamem.2007.09.003","article-title":"Endothelial Adherens and Tight Junctions in Vascular Homeostasis, Inflammation and Angiogenesis","volume":"1778","author":"Wallez","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.4161\/cam.29026","article-title":"Endothelial Permeability and VE-Cadherin: A Wacky Comradeship","volume":"8","author":"Gavard","year":"2014","journal-title":"Cell Adh Migr"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020364","article-title":"Molecular Insights Into the Thrombotic and Microvascular Injury in Placental Endothelium of Women With Mild or Severe COVID-19","volume":"10","author":"Flores-Pliego","year":"2021","journal-title":"Cells"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.074500","article-title":"Study of GPR81, the Lactate Receptor, From Distant Species Identifies Residues and Motifs Critical for GPR81 Functions","volume":"80","author":"Kuei","year":"2011","journal-title":"Mol Pharmacol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.316925","article-title":"Interleukin-1ra Mitigates SARS-CoV-2-Induced Inflammatory Lung Vascular Leakage and Mortality in Humanized K18-hACE-2 Mice","volume":"41","author":"Xiong","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136908","article-title":"IL-1beta Suppression of VE-Cadherin Transcription Underlies Sepsis-Induced Inflammatory Lung Injury","volume":"130","author":"Xiong","year":"2020","journal-title":"J Clin Invest"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.019650","article-title":"Coronavirus Disease 2019-Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management","volume":"10","author":"Ortega-Paz","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.7326\/L20-1206","article-title":"Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study","volume":"173","author":"Wichmann","year":"2020","journal-title":"Ann Intern Med"},{"key":"B148","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1001\/jama.2020.13372","article-title":"Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System","volume":"324","author":"Bilaloglu","year":"2020","journal-title":"JAMA"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v8.i19.4370","article-title":"Prolonged Prothrombin Time at Admission Predicts Poor Clinical Outcome in COVID-19 Patients","volume":"8","author":"Wang","year":"2020","journal-title":"World J Clin Cases"},{"key":"B150","doi-asserted-by":"publisher","first-page":"6159720","DOI":"10.1155\/2020\/6159720","article-title":"D-Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID-19 and Poor Prognosis","volume":"2020","author":"Long","year":"2020","journal-title":"BioMed Res Int"},{"key":"B151","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13045-020-00954-7","article-title":"SARS-CoV-2 Binds Platelet ACE2 to Enhance Thrombosis in COVID-19","volume":"13","author":"Zhang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319117","article-title":"SARS-CoV-2 Initiates Programmed Cell Death in Platelets","volume":"129","author":"Koupenova","year":"2021","journal-title":"Circ Res"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006000","article-title":"COVID-19 and its Implications for Thrombosis and Anticoagulation","volume":"135","author":"Connors","year":"2020","journal-title":"Blood"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2103417","article-title":"Therapeutic Anticoagulation With Heparin in Critically Ill Patients With Covid-19","volume":"385","author":"Goligher","year":"2021","journal-title":"N\u00a0Engl J Med"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.08.010","article-title":"Heparin Failure and COVID-19: Should We Explore Other Anticoagulants? An Observational Report Regarding in-Vitro Recovery of Anticoagulant Action in COVID-19 Patients in Intensive Care","volume":"195","author":"Thomas","year":"2020","journal-title":"Thromb Res"},{"key":"B156","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1007\/s11239-020-02196-3","article-title":"Correction to: Heparin Resistance in COVID19 Patients in the Intensive Care Unit","volume":"50","author":"White","year":"2020","journal-title":"J Thromb Thrombolysis"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2020.09.012","article-title":"Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients","volume":"136","author":"Daniels","year":"2020","journal-title":"Am J Cardiol"},{"key":"B158","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.jamda.2020.06.018","article-title":"The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents","volume":"21","author":"De Spiegeleer","year":"2020","journal-title":"J Am Med Dir Assoc"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.3594","article-title":"Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-Analysis","volume":"4","author":"Baral","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.9.2029","article-title":"Hypoxia\/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis","volume":"19","author":"Yan","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11080495","article-title":"Metabolomic Profile in Venous Thromboembolism (VTE)","volume":"11","author":"Franczyk","year":"2021","journal-title":"Metabolites"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.03.011","article-title":"Higher Lactate and Purine Metabolite Levels in Erythrocyte-Rich Fresh Venous Thrombus: Potential Markers for Early Deep Vein Thrombosis","volume":"177","author":"Maekawa","year":"2019","journal-title":"Thromb Res"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw550","article-title":"Thrombosis and Platelets: An Update","volume":"38","author":"Koupenova","year":"2017","journal-title":"Eur Heart J"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2005.09.008","article-title":"Lactate Production by Thrombin-Activated Platelets of Patients With Primary Thrombocythemia","volume":"118","author":"Cesar","year":"2006","journal-title":"Thromb Res"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.205724","article-title":"Aerobic Glycolysis Fuels Platelet Activation: Small-Molecule Modulators of Platelet Metabolism as Anti-Thrombotic Agents","volume":"104","author":"Kulkarni","year":"2019","journal-title":"Haematologica"},{"key":"B166","doi-asserted-by":"publisher","first-page":"1076029620933945","DOI":"10.1177\/1076029620933945","article-title":"COVID-19 May Predispose to Thrombosis by Affecting Both Vascular Endothelium and Platelets","volume":"26","author":"Cure","year":"2020","journal-title":"Clin Appl Thromb Hemost"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.12.023","article-title":"Na(+)\/H(+) Exchanger in the Regulation of Platelet Activation and Paradoxical Effects of Cariporide","volume":"272","author":"Chang","year":"2015","journal-title":"Exp Neurol"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9040953","article-title":"Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated With Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation","volume":"9","author":"Zabczyk","year":"2020","journal-title":"J Clin Med"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76344","article-title":"Cytosolic HMGB1 Controls the Cellular Autophagy\/Apoptosis Checkpoint During Inflammation","volume":"125","author":"Zhu","year":"2015","journal-title":"J Clin Invest"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1134\/S0026893318050096","article-title":"[HMGB Proteins as DNA Chaperones That Modulate Chromatin Activity]","volume":"52","author":"Kozlova","year":"2018","journal-title":"Mol Biol (Mosk)"},{"key":"B171","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbagrm.2009.09.001","article-title":"Nuclear Functions of the HMG Proteins","volume":"1799","author":"Reeves","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"B172","doi-asserted-by":"publisher","DOI":"10.1080\/00365540310016286","article-title":"HMGB1 in Sepsis","volume":"35","author":"Andersson","year":"2003","journal-title":"Scand J Infect Dis"},{"key":"B173","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0495","article-title":"HMGB1 in Cancer: Good, Bad, or Both","volume":"19","author":"Kang","year":"2013","journal-title":"Clin Cancer Res"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.10.010","article-title":"Role of HMGB1 in Cardiovascular Diseases","volume":"6","author":"Li","year":"2006","journal-title":"Curr Opin Pharmacol"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e05672","article-title":"HMGB1 as a Potential Biomarker and Therapeutic Target for Severe COVID-19","volume":"6","author":"Chen","year":"2020","journal-title":"Heliyon"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0492-x","article-title":"Elevated Serum Levels of S100A8\/A9 and HMGB1 at Hospital Admission are Correlated With Inferior Clinical Outcomes in COVID-19 Patients","volume":"17","author":"Chen","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B177","doi-asserted-by":"publisher","first-page":"4436","DOI":"10.1038\/ncomms5436","article-title":"PKM2 Regulates the Warburg Effect and Promotes HMGB1 Release in Sepsis","volume":"5","author":"Yang","year":"2014","journal-title":"Nat Commun"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316925111","article-title":"JAK\/STAT1 Signaling Promotes HMGB1 Hyperacetylation and Nuclear Translocation","volume":"111","author":"Lu","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400359","article-title":"PARP-1 Mediates LPS-Induced HMGB1 Release by Macrophages Through Regulation of HMGB1 Acetylation","volume":"193","author":"Yang","year":"2014","journal-title":"J Immunol"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701465200","article-title":"Activation of Poly(ADP)-Ribose Polymerase (PARP-1) Induces Release of the Pro-Inflammatory Mediator HMGB1 From the Nucleus","volume":"282","author":"Ditsworth","year":"2007","journal-title":"J Biol Chem"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg516","article-title":"Monocytic Cells Hyperacetylate Chromatin Protein HMGB1 to Redirect it Towards Secretion","volume":"22","author":"Bonaldi","year":"2003","journal-title":"EMBO J"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00854","article-title":"Evidence for Sirt1 Mediated Hmgb1 Release from Kidney Cells in the Early Stages of Hemorrhagic Shock","volume":"10","author":"Xu","year":"2019","journal-title":"Front Physiol"},{"key":"B183","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.molimm.2019.02.008","article-title":"Heat Shock Protein 27 Inhibits HMGB1 Translocation by Regulating CBP Acetyltransferase Activity and Ubiquitination","volume":"108","author":"Bi","year":"2019","journal-title":"Mol Immunol"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26341","article-title":"HMGB1 Contributes to the Irradiation-Induced Endothelial Barrier Injury Through Receptor for Advanced Glycation Endproducts (RAGE)","volume":"233","author":"Zhou","year":"2018","journal-title":"J Cell Physiol"},{"key":"B185","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1016\/j.cmet.2021.09.009","article-title":"Hyperglycemia in Acute COVID-19 is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2","volume":"33","author":"Reiterer","year":"2021","journal-title":"Cell Metab"},{"key":"B186","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.eprac.2020.12.015","article-title":"Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19","volume":"27","author":"Mazori","year":"2021","journal-title":"Endocr Pract"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.3390\/nu13072199","article-title":"Association Between Hyperglycemia at Hospital Presentation and Hospital Outcomes in COVID-19 Patients With and Without Type 2 Diabetes: A Retrospective Cohort Study of Hospitalized Inner-City COVID-19 Patients","volume":"13","author":"Charoenngam","year":"2021","journal-title":"Nutrients"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27556","article-title":"Hyperglycemia and Blood Glucose Deterioration are Risk Factors for Severe COVID-19 With Diabetes: A Two-Center Cohort Study","author":"Xiao","year":"2021","journal-title":"J Med Virol"},{"key":"B189","doi-asserted-by":"publisher","first-page":"3896147","DOI":"10.1155\/2016\/3896147","article-title":"High Mobility Group Box-1: A Missing Link Between Diabetes and Its Complications","volume":"2016","author":"Wu","year":"2016","journal-title":"Mediators Inflamm"},{"key":"B190","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1038\/s41598-018-20479-x","article-title":"Deep Vein Thrombosis in Mice is Regulated by Platelet HMGB1 Through Release of Neutrophil-Extracellular Traps and DNA","volume":"8","author":"Dyer","year":"2018","journal-title":"Sci Rep"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-710632","article-title":"Disulfide HMGB1 Derived From Platelets Coordinates Venous Thrombosis in Mice","volume":"128","author":"Stark","year":"2016","journal-title":"Blood"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81660","article-title":"Platelet-Derived HMGB1 is a Critical Mediator of Thrombosis","volume":"125","author":"Vogel","year":"2015","journal-title":"J Clin Invest"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-11-0759","article-title":"High-Mobility Group Box 1 Protein Induces Tissue Factor Expression in Vascular Endothelial Cells via Activation of NF-kappaB and Egr-1","volume":"102","author":"Lv","year":"2009","journal-title":"Thromb Haemost"},{"key":"B194","doi-asserted-by":"publisher","first-page":"110520","DOI":"10.1016\/j.mehy.2021.110520","article-title":"The Potential Use of Lactate Blockers for the Prevention of COVID-19 Worst Outcome, Insights From Exercise Immunology","volume":"148","author":"AbdelMassih","year":"2021","journal-title":"Med Hypotheses"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21010234","article-title":"2-Deoxy-D-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents","volume":"21","author":"Pajak","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix138","article-title":"Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis","volume":"215","author":"Zheng","year":"2017","journal-title":"J\u00a0Infect Dis"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_1338_21","article-title":"Role of 2-Deoxy-D-Glucose (2-DG) in COVID-19 Disease: A Potential Game-Changer","volume":"10","author":"Sahu","year":"2021","journal-title":"J Family Med Prim Care"},{"key":"B198","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.271.1.E143","article-title":"Role of the Lactate Transporter (MCT1) in Skeletal Muscles","volume":"271","author":"McCullagh","year":"1996","journal-title":"Am J Physiol"},{"key":"B199","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2003.09.007","article-title":"Modulating Toll-Like Receptor Mediated Signaling by (1\u2013>3)-Beta-D-Glucan Rapidly Induces Cardioprotection","volume":"61","author":"Li","year":"2004","journal-title":"Cardiovasc Res"},{"key":"B200","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01007.2010","article-title":"Glucan Phosphate Attenuates Myocardial HMGB1 Translocation in Severe Sepsis Through Inhibiting NF-kappaB Activation","volume":"301","author":"Ha","year":"2011","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B201","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.cell.2022.01.009","article-title":"An Adjuvant Strategy Enabled by Modulation of the Physical Properties of Microbial Ligands Expands Antigen Immunogenicity","volume":"185","author":"Borriello","year":"2022","journal-title":"Cell"},{"key":"B202","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging Concepts in the Science of Vaccine Adjuvants","volume":"20","author":"Pulendran","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B203","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182312636","article-title":"Beta-Glucans Could Be Adjuvants for SARS-CoV-2 Virus Vaccines (COVID-19)","volume":"18","author":"Cordova-Martinez","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"B204","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.624698","article-title":"Metabolic Alterations in SARS-CoV-2 Infection and Its Implication in Kidney Dysfunction","volume":"12","author":"Andrade Silva","year":"2021","journal-title":"Front Physiol"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0237-2","article-title":"A Metabolic Handbook for the COVID-19 Pandemic","volume":"2","author":"Ayres","year":"2020","journal-title":"Nat Metab"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.868679\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T21:56:43Z","timestamp":1648504603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.868679\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,23]]},"references-count":205,"alternative-id":["10.3389\/fimmu.2022.868679"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.868679","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,23]]},"article-number":"868679"}}