Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
Raffaele Izzo, Valentina Trimarco, Pasquale Mone, Massimo Teresita Aloè, Massimo Capra Marzani, Antonio Diana, Giovanni Fazio, Mario Mallardo, Mauro Maniscalco, Giuseppe Marazzi, Nunzia Messina, Simone Mininni, Chiara Mussi, Girolamo Pelaia, Alfio Pennisi, Pierachille Santus, Francesco Scarpelli, Francesco Tursi, Alessandro Zanforlin, Gaetano Santulli, Bruno Trimarco
Pharmacological Research, doi:10.1016/j.phrs.2022.106360
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Flow chart of the study. J o u r n a l P r e -p r o o f
References
Ahmetaj-Shala, Cardiorenal Tissues Express SARS-CoV-2 Entry Genes and Basigin (BSG/CD147) Increases With Age in Endothelial Cells, JACC Basic Transl Sci,
doi:10.1016/j.jacbts.2020.09.010Amraei, Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells, Proc Natl Acad Sci U S A,
doi:10.1073/pnas.2113874119Azizi, Azizi, Neurological injuries in COVID-19 patients: direct viral invasion or a bystander injury after infection of epithelial/endothelial cells, J Neurovirol,
doi:10.1007/s13365-020-00903-7Boggiano, Update on and Future Directions for Use of Anti-SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19, Ann Intern Med,
doi:10.7326/M21-3669Bronte, Zanovello, Regulation of immune responses by L-arginine metabolism, Nat Rev Immunol,
doi:10.1038/nri1668Budinger, Misharin, Ridge, Singer, Wunderink, Distinctive features of severe SARS-CoV-2 pneumonia, J Clin Invest,
doi:10.1172/JCI149412Burkhard-Koren, Higher prevalence of pulmonary macrothrombi in SARS-CoV-2 than in influenza A: autopsy results from 'Spanish flu' 1918/1919 in Switzerland to Coronavirus disease 2019, J Pathol Clin Res,
doi:10.1002/cjp2.189Carr, Rowe, The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19, Nutrients,
doi:10.3390/nu12113286Ceriello, Combined effect of metformin with ascorbic acid versus acetyl salicylic acid on diabetes-related cardiovascular complication; a 12-month single blind multicenter randomized control trial, Cardiovasc Diabetol,
doi:10.2337/dc13-0750Charfeddine, Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study, Front Cardiovasc Med,
doi:10.3389/fcvm.2021.745758Chavarria, Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19, Comput Struct Biotechnol J,
doi:10.1016/j.csbj.2021.02.009Chioh, Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation, Elife,
doi:10.7554/eLife.64909Cinar, Iyer, Kunos, Dual inhibition of CB1 receptors and iNOS, as a potential novel approach to the pharmacological management of acute and long COVID-19
Crook, Raza, Nowell, Young, Edison, Long covid-mechanisms, risk factors, and management, BMJ,
doi:10.1136/bmj.n1648Dean, Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19, medRxiv,
doi:10.1101/2021.03.26.21254441Fauci, Lane, Redfield, Covid-19 -Navigating the Uncharted, The New England journal of medicine,
doi:10.1056/NEJMe2002387Fiorentino, Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of J o u r n a l P r e -p r o o f the first interim analysis, EClinicalMedicine,
doi:10.1016/j.eclinm.2021.101125Fogarty, Persistent endotheliopathy in the pathogenesis of long COVID syndrome, J Thromb Haemost,
doi:10.1111/jth.15490Gambardella, Santulli, What is linking COVID-19 and endothelial dysfunction? Updates on nanomedicine and bioengineering from the 2020 AHA Scientific Sessions, European Heart Journal (Cardiovascular Pharmacotherapy)
Garcia, Immune Response, Inflammation, and the Clinical Spectrum of COVID-19
Gelzo, Inducible Nitric Oxide Synthase (iNOS): Why a Different Production in COVID-19 Patients of the Two Waves?, Viruses,
doi:10.3390/v14030534Guervilly, Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19, J Infect Dis,
doi:10.1093/infdis/jiaa528Hoehl, Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China, The New England journal of medicine,
doi:10.1056/NEJMc2001899Isidori, Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection. The DEDALO project, Andrology,
doi:10.1111/andr.12837J O U R N A L P R E -P R O O F Castanares-Zapatero, Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates, Nat Commun,
doi:10.1080/07853890.2022.2076901J O U R N A L P R E -P R O O F Datta, Talwar, Lee, A Proposed Framework and Timeline of the Spectrum of Disease Due to SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health Implications, JAMA,
doi:10.1001/jama.2020.22717J O U R N A L P R E -P R O O F Dormanns, Brown, David, The role of nitric oxide in neurovascular coupling, J Theor Biol,
doi:10.1016/j.jtbi.2016.01.009J O U R N A L P R E -P R O O F Perea Polak, Complement-mediated thrombogenic vasculopathy in COVID-19, Int J Dermatol,
doi:10.1111/ijd.15267J O U R N A L P R E -P R O O F Srivastava, Garg, Hembrom, Kumar, Assessment of nitric oxide (NO) potential to mitigate COVID-19 severity, Virusdisease,
doi:10.1007/s13337-021-00702-6J O U R N A L P R E -P R O O F Varzideh, Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress, J Clin Invest,
doi:10.1172/JCI156624Johansson, The effect of prostacyclin (Iloprost) infusion at a dose of 1 ng/kg/min for 72 hours compared to placebo in mechanically ventilated patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial, Trials,
doi:10.1186/s13063-020-04696-2Jorens, Vermeire, Herman, L-arginine-dependent nitric oxide synthase: a new metabolic pathway in the lung and airways, Eur Respir J
Kelliher, Non-severe COVID-19 is associated with endothelial damage and hypercoagulability despite pharmacological thromboprophylaxis, J Thromb Haemost,
doi:10.1111/jth.15660Kuck, Effects of L-arginine on cerebral blood flow, microvascular permeability, number of perfused capillaries, and brain water content in the traumatized mouse brain, Biochem Biophys Res Commun,
doi:10.1016/j.bbrc.2017.11.058Lavine, Bjornstad, Antia, Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury, Front Immunol,
doi:10.1126/science.abe6522Leucker, Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial, JACC Basic Transl Sci,
doi:10.1016/j.jacbts.2021.09.013Liu, Zhu, Zhang, Li, Peng, Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial, BMJ Open,
doi:10.1136/bmjopen-2020-039519Ma, Yang, Huang, Lui, Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications, J Mol Cell Cardiol,
doi:10.1016/j.yjmcc.2021.11.010Manson, COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study, Lancet Rheumatol,
doi:10.1016/S2665-9913(20)30275-7Matarese, Gambardella, Sardu, Santulli, miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key Implications for COVID-19, Biomedicines,
doi:10.3390/biomedicines8110462May, Qu, Maggini, Nitric oxide mediates tightening of the endothelial barrier by ascorbic acid, Vitamin C and Immune Function,
doi:10.1016/j.bbrc.2010.12.046Mesquida, Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units, Crit Care,
doi:10.1186/s13054-021-03803-2Mone, L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19
Mone, miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells, Front Cardiovasc Med,
doi:10.3390/ncrna7010009Morelli, Gambardella, Castellanos, Trimarco, Santulli, Vitamin C and Cardiovascular Disease: An Update, Antioxidants,
doi:10.3390/antiox9121227Nagashima, Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report, Arterioscler Thromb Vasc Biol,
doi:10.1161/ATVBAHA.120.314860Oikonomou, Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study, Vascul Pharmacol,
doi:10.1016/j.vph.2022.106975Ortiz, The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells, EBioMedicine,
doi:10.1016/j.ebiom.2020.102976Page, Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: an observational cohort study, BMJ Open,
doi:10.1136/bmjopen-2021-055137Qin, Endothelial cell infection and dysfunction, immune activation in severe COVID-19, Theranostics,
doi:10.7150/thno.61810Rath, Muller, Kropf, Closs, Munder, Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages, Front Immunol,
doi:10.3389/fimmu.2014.00532Raveendran, Misra, Post COVID-19 Syndrome ("Long COVID") and Diabetes: Challenges in Diagnosis and Management, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2021.102235Reizine, SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage, J Clin Immunol,
doi:10.1007/s10875-020-00920-5Sacchi, Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection, Cells,
doi:10.3390/cells10082111Santulli, Morelli, Gambardella, Is Endothelial Dysfunction the Concealed Cornerstone of COVID-19?, BMJ
Sardu, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence, J Clin Med,
doi:10.3390/jcm9051417Sardu, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence, J Clin Med,
doi:10.3390/jcm9051417Sharma, A randomized open-label trial to evaluate the efficacy and safety of triple therapy with aspirin, atorvastatin, and nicorandil in hospitalised patients with SARS Cov-2 infection: A structured summary of a study protocol for a randomized controlled trial, Trials,
doi:10.1186/s13063-021-05361-ySheahan, Frieman, The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health, Curr Opin Virol,
doi:10.1016/j.coviro.2020.05.010Sievers, Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses, Sci Transl Med,
doi:10.1126/scitranslmed.abn7842Soto, Guarner-Lans, Soria-Castro, Manzano Pech, Perez-Torres et al., Is Antioxidant Therapy a Useful Complementary Measure for Covid-19 Treatment? An Algorithm for Its Application, Medicina,
doi:10.3390/medicina56080386Stephenson, Levin, Spector, Lis, Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer, Cancer Chemother Pharmacol,
doi:10.1007/s00280-013-2179-9Ströhle, Von Bibra, Hahn, L-Arginine and vascular health
Suh, Intravenous vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial, Nutr J,
doi:10.1186/1475-2891-11-7Tousoulis, Kampoli, Tentolouris, Papageorgiou, Stefanadis, The role of nitric oxide on endothelial function, Curr Vasc Pharmacol,
doi:10.2174/157016112798829760Vollenberg, Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 Patients: A Prospective Multicenter Study and Hypothesis, Viruses,
doi:10.3390/v13112324Wang, Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2022.861703Wijnands, Castermans, Hommen, Meesters, Poeze, Arginine and citrulline and the immune response in sepsis, Nutrients,
doi:10.3390/nu7031426Yan, Tie, Messina, Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to decrease oxidative stress, increase nitricoxide and improve blood flow after induction of hindlimbischemia in the rat, Mol Med,
doi:10.2119/molmed.2011.00103Zou, SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients, The New England journal of medicine,
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'doi-asserted-by': 'crossref',
'first-page': 'C1',
'DOI': '10.1152/ajpcell.00375.2021',
'article-title': 'Long-term complications of COVID-19',
'volume': '322',
'author': 'Desai',
'year': '2022',
'journal-title': 'Am J Physiol Cell Physiol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib8',
'doi-asserted-by': 'crossref',
'article-title': 'Long-term Health Consequences of COVID-19',
'author': 'Del Rio',
'year': '2020',
'journal-title': 'JAMA',
'DOI': '10.1001/jama.2020.19719'},
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'doi-asserted-by': 'crossref',
'first-page': '5',
'DOI': '10.1016/j.amjmed.2021.07.037',
'article-title': 'The Long COVID Conundrum',
'volume': '135',
'author': 'Gaffney',
'year': '2022',
'journal-title': 'Am J Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib10',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.dsx.2021.102235',
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'Diagnosis and Management',
'volume': '15',
'author': 'Raveendran',
'year': '2021',
'journal-title': 'Diabetes Metab Syndr'},
{ 'key': '10.1016/j.phrs.2022.106360_bib11',
'doi-asserted-by': 'crossref',
'first-page': 'o143',
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'doi-asserted-by': 'crossref',
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'author': 'Nalbandian',
'year': '2021',
'journal-title': 'Nat Med'},
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'doi-asserted-by': 'crossref',
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'DOI': '10.1001/jama.2020.22130',
'article-title': 'Reflections of a COVID-19 Long Hauler',
'volume': '324',
'author': 'Siegelman',
'year': '2020',
'journal-title': 'JAMA'},
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'doi-asserted-by': 'crossref',
'first-page': '2549',
'DOI': '10.2337/dbi20-0032',
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'author': 'Feldman',
'year': '2020',
'journal-title': 'Diabetes'},
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'volume': '15',
'author': 'Raveendran',
'year': '2021',
'journal-title': 'Diabetes Metab Syndr'},
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'DOI': '10.1371/journal.pmed.1003571',
'article-title': 'COVID-19 and excess mortality in the United States: A county-level '
'analysis',
'volume': '18',
'author': 'Stokes',
'year': '2021',
'journal-title': 'PLoS Med'},
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'first-page': '693',
'DOI': '10.1111/1753-0407.13187',
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'author': 'Sathish',
'year': '2021',
'journal-title': 'J Diabetes'},
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'doi-asserted-by': 'crossref',
'article-title': 'Acute and long-term disruption of glycometabolic control after '
'SARS-CoV-2 infection',
'author': 'Montefusco',
'year': '2021',
'journal-title': 'Nat Metab',
'DOI': '10.1038/s42255-021-00407-6'},
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'doi-asserted-by': 'crossref',
'first-page': '1268',
'DOI': '10.1056/NEJMe2002387',
'article-title': 'Covid-19 - Navigating the Uncharted',
'volume': '382',
'author': 'Fauci',
'year': '2020',
'journal-title': 'The New England journal of medicine'},
{ 'key': '10.1016/j.phrs.2022.106360_bib20',
'first-page': '493',
'article-title': 'COVID-19: The therapeutic landscape',
'volume': '2',
'author': 'Paules',
'year': '2021',
'journal-title': 'Med (N Y)'},
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'doi-asserted-by': 'crossref',
'first-page': '1278',
'DOI': '10.1056/NEJMc2001899',
'article-title': 'Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, '
'China',
'volume': '382',
'author': 'Hoehl',
'year': '2020',
'journal-title': 'The New England journal of medicine'},
{ 'key': '10.1016/j.phrs.2022.106360_bib22',
'doi-asserted-by': 'crossref',
'first-page': '1177',
'DOI': '10.1056/NEJMc2001737',
'article-title': 'SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected '
'Patients',
'volume': '382',
'author': 'Zou',
'year': '2020',
'journal-title': 'The New England journal of medicine'},
{ 'key': '10.1016/j.phrs.2022.106360_bib23',
'doi-asserted-by': 'crossref',
'first-page': '37',
'DOI': '10.1016/j.coviro.2020.05.010',
'article-title': 'The continued epidemic threat of SARS-CoV-2 and implications for the '
'future of global public health',
'volume': '40',
'author': 'Sheahan',
'year': '2020',
'journal-title': 'Curr Opin Virol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib24',
'doi-asserted-by': 'crossref',
'first-page': '141',
'DOI': '10.1038/s41579-020-00459-7',
'article-title': 'Characteristics of SARS-CoV-2 and COVID-19',
'volume': '19',
'author': 'Hu',
'year': '2021',
'journal-title': 'Nat Rev Microbiol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib25',
'doi-asserted-by': 'crossref',
'first-page': '123',
'DOI': '10.1038/s42255-020-00339-7',
'article-title': 'Can COVID-19 cause diabetes',
'volume': '3',
'author': 'Accili',
'year': '2021',
'journal-title': 'Nat Metab'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1001/jamanetworkopen.2021.40568',
'article-title': 'Metabolic Syndrome and Acute Respiratory Distress Syndrome in '
'Hospitalized Patients With COVID-19',
'volume': '4',
'author': 'Denson',
'year': '2021',
'journal-title': 'JAMA Netw Open'},
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'doi-asserted-by': 'crossref',
'first-page': '1017',
'DOI': '10.1038/s41591-020-0968-3',
'article-title': 'Extrapulmonary manifestations of COVID-19',
'volume': '26',
'author': 'Gupta',
'year': '2020',
'journal-title': 'Nat Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib28',
'doi-asserted-by': 'crossref',
'first-page': '1417',
'DOI': '10.3390/jcm9051417',
'article-title': 'Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an '
'Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic '
'Evidence',
'volume': '9',
'author': 'Sardu',
'year': '2020',
'journal-title': 'J Clin Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib29',
'article-title': 'Is Endothelial Dysfunction the Concealed Cornerstone of COVID-19?',
'volume': '368',
'author': 'Santulli',
'year': '2020',
'journal-title': 'BMJ'},
{ 'key': '10.1016/j.phrs.2022.106360_bib30',
'doi-asserted-by': 'crossref',
'first-page': '8076',
'DOI': '10.7150/thno.61810',
'article-title': 'Endothelial cell infection and dysfunction, immune activation in severe '
'COVID-19',
'volume': '11',
'author': 'Qin',
'year': '2021',
'journal-title': 'Theranostics'},
{ 'key': '10.1016/j.phrs.2022.106360_bib31',
'doi-asserted-by': 'crossref',
'first-page': '3038',
'DOI': '10.1093/eurheartj/ehaa623',
'article-title': 'COVID-19 is, in the end, an endothelial disease',
'volume': '41',
'author': 'Libby',
'year': '2020',
'journal-title': 'Eur Heart J'},
{ 'key': '10.1016/j.phrs.2022.106360_bib32',
'article-title': 'Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 '
'thromboinflammation',
'author': 'Gu',
'year': '2020',
'journal-title': 'Nat Rev Cardiol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib33',
'article-title': 'Complement-mediated thrombogenic vasculopathy in COVID-19',
'author': 'Perea Polak',
'year': '2020',
'journal-title': 'Int J Dermatol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib34',
'doi-asserted-by': 'crossref',
'first-page': '389',
'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': '10.1016/j.phrs.2022.106360_bib35',
'doi-asserted-by': 'crossref',
'first-page': '381',
'DOI': '10.1186/s13054-021-03803-2',
'article-title': 'Peripheral microcirculatory alterations are associated with the '
'severity of acute respiratory distress syndrome in COVID-19 patients '
'admitted to intermediate respiratory and intensive care units',
'volume': '25',
'author': 'Mesquida',
'year': '2021',
'journal-title': 'Crit Care'},
{ 'key': '10.1016/j.phrs.2022.106360_bib36',
'doi-asserted-by': 'crossref',
'DOI': '10.1172/jci.insight.151527',
'article-title': 'Tie2 activation protects against prothrombotic endothelial dysfunction '
'in COVID-19',
'volume': '6',
'author': 'Schmaier',
'year': '2021',
'journal-title': 'JCI Insight'},
{ 'key': '10.1016/j.phrs.2022.106360_bib37',
'doi-asserted-by': 'crossref',
'article-title': 'Endothelial Dysfunction in Covid-19',
'author': 'Otifi',
'year': '2022',
'journal-title': 'Am J Med Sci',
'DOI': '10.1016/j.amjms.2021.12.010'},
{ 'key': '10.1016/j.phrs.2022.106360_bib38',
'doi-asserted-by': 'crossref',
'article-title': 'Non-severe COVID-19 is associated with endothelial damage and '
'hypercoagulability despite pharmacological thromboprophylaxis',
'author': 'Kelliher',
'year': '2022',
'journal-title': 'J Thromb Haemost',
'DOI': '10.1111/jth.15660'},
{ 'key': '10.1016/j.phrs.2022.106360_bib39',
'doi-asserted-by': 'crossref',
'DOI': '10.1073/pnas.2113874119',
'article-title': 'Extracellular vimentin is an attachment factor that facilitates '
'SARS-CoV-2 entry into human endothelial cells',
'volume': '119',
'author': 'Amraei',
'year': '2022',
'journal-title': 'Proc Natl Acad Sci U S A'},
{ 'key': '10.1016/j.phrs.2022.106360_bib40',
'doi-asserted-by': 'crossref',
'unstructured': 'Gambardella, J. & Santulli, G. What is linking COVID-19 and endothelial '
'dysfunction? Updates on nanomedicine and bioengineering from the 2020 '
'AHA Scientific Sessions. European Heart Journal (Cardiovascular '
'Pharmacotherapy), In press (2020).',
'DOI': '10.1093/ehjcvp/pvaa145'},
{ 'key': '10.1016/j.phrs.2022.106360_bib41',
'doi-asserted-by': 'crossref',
'first-page': '989',
'DOI': '10.3389/fphys.2020.00989',
'article-title': 'The Enigma of Endothelium in COVID-19',
'volume': '11',
'author': 'Kaur',
'year': '2020',
'journal-title': 'Front Physiol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib42',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/biomedicines8110462',
'article-title': 'miR-98 Regulates TMPRSS2 Expression in Human Endothelial Cells: Key '
'Implications for COVID-19',
'volume': '8',
'author': 'Matarese',
'year': '2020',
'journal-title': 'Biomedicines'},
{ 'key': '10.1016/j.phrs.2022.106360_bib43',
'doi-asserted-by': 'crossref',
'first-page': '1111',
'DOI': '10.1016/j.jacbts.2020.09.010',
'article-title': 'Cardiorenal Tissues Express SARS-CoV-2 Entry Genes and Basigin '
'(BSG/CD147) Increases With Age in Endothelial Cells',
'volume': '5',
'author': 'Ahmetaj-Shala',
'year': '2020',
'journal-title': 'JACC Basic Transl Sci'},
{ 'key': '10.1016/j.phrs.2022.106360_bib44',
'article-title': 'miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human '
'Brain Microvascular Endothelial Cells',
'volume': '7',
'author': 'Mone',
'year': '2021',
'journal-title': 'Noncoding RNA'},
{ 'key': '10.1016/j.phrs.2022.106360_bib45',
'doi-asserted-by': 'crossref',
'DOI': '10.3389/fcvm.2020.598400',
'article-title': 'Vascular Manifestations of COVID-19 - Thromboembolism and Microvascular '
'Dysfunction',
'volume': '7',
'author': 'Roberts',
'year': '2020',
'journal-title': 'Front Cardiovasc Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib46',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.ebiom.2020.102976',
'article-title': 'Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the '
'human respiratory tract',
'volume': '60',
'author': 'Ortiz',
'year': '2020',
'journal-title': 'EBioMedicine'},
{ 'key': '10.1016/j.phrs.2022.106360_bib47',
'doi-asserted-by': 'crossref',
'first-page': '2214',
'DOI': '10.1080/21505594.2021.1964329',
'article-title': 'The ApoA-I mimetic peptide 4F attenuates in vitro replication of '
'SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in '
'epithelial cells',
'volume': '12',
'author': 'Kelesidis',
'year': '2021',
'journal-title': 'Virulence'},
{ 'key': '10.1016/j.phrs.2022.106360_bib48',
'doi-asserted-by': 'crossref',
'DOI': '10.1172/JCI156624',
'article-title': 'Sortilin drives hypertension by modulating sphingolipid/ceramide '
'homeostasis and by triggering oxidative stress',
'volume': '132',
'author': 'Varzideh',
'year': '2022',
'journal-title': 'J Clin Invest'},
{ 'key': '10.1016/j.phrs.2022.106360_bib49',
'doi-asserted-by': 'crossref',
'first-page': '1625',
'DOI': '10.1161/HYPERTENSIONAHA.120.15130',
'article-title': 'Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema',
'volume': '76',
'author': 'Gambardella',
'year': '2020',
'journal-title': 'Hypertension'},
{ 'key': '10.1016/j.phrs.2022.106360_bib50',
'doi-asserted-by': 'crossref',
'first-page': '477',
'DOI': '10.1161/CIRCRESAHA.118.313237',
'article-title': 'Emerging Roles of Vascular Endothelium in Metabolic Homeostasis',
'volume': '123',
'author': 'Pi',
'year': '2018',
'journal-title': 'Circ Res'},
{ 'key': '10.1016/j.phrs.2022.106360_bib51',
'doi-asserted-by': 'crossref',
'first-page': '114',
'DOI': '10.1161/CIRCULATIONAHA.120.046702',
'article-title': 'Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, '
'China: Prevalence, Risk Factors, and Outcome',
'volume': '142',
'author': 'Zhang',
'year': '2020',
'journal-title': 'Circulation'},
{ 'key': '10.1016/j.phrs.2022.106360_bib52',
'doi-asserted-by': 'crossref',
'first-page': '2404',
'DOI': '10.1161/ATVBAHA.120.314860',
'article-title': 'Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief '
'Report',
'volume': '40',
'author': 'Nagashima',
'year': '2020',
'journal-title': 'Arterioscler Thromb Vasc Biol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib53',
'article-title': 'Higher prevalence of pulmonary macrothrombi in SARS-CoV-2 than in '
"influenza A: autopsy results from 'Spanish flu' 1918/1919 in "
'Switzerland to Coronavirus disease 2019',
'author': 'Burkhard-Koren',
'year': '2020',
'journal-title': 'J Pathol Clin Res'},
{ 'key': '10.1016/j.phrs.2022.106360_bib54',
'doi-asserted-by': 'crossref',
'DOI': '10.1371/journal.pone.0241955',
'article-title': 'Prognostic factors for severity and mortality in patients infected with '
'COVID-19: A systematic review',
'volume': '15',
'author': 'Izcovich',
'year': '2020',
'journal-title': 'PLoS One'},
{ 'key': '10.1016/j.phrs.2022.106360_bib55',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.eclinm.2021.101125',
'article-title': 'Effects of adding L-arginine orally to standard therapy in patients '
'with COVID-19: A randomized, double-blind, placebo-controlled, '
'parallel-group trial. Results of the first interim analysis',
'volume': '40',
'author': 'Fiorentino',
'year': '2021',
'journal-title': 'EClinicalMedicine'},
{ 'key': '10.1016/j.phrs.2022.106360_bib56',
'doi-asserted-by': 'crossref',
'first-page': '746',
'DOI': '10.1186/s13063-020-04696-2',
'article-title': 'The effect of prostacyclin (Iloprost) infusion at a dose of 1 ng/kg/min '
'for 72 hours compared to placebo in mechanically ventilated patients '
'with COVID-19: A structured summary of a study protocol for a '
'randomized controlled trial',
'volume': '21',
'author': 'Johansson',
'year': '2020',
'journal-title': 'Trials'},
{ 'key': '10.1016/j.phrs.2022.106360_bib57',
'article-title': 'Intravenous high-dose vitamin C for the treatment of severe COVID-19: '
'study protocol for a multicentre randomised controlled trial',
'volume': '10',
'author': 'Liu',
'year': '2020',
'journal-title': 'BMJ Open'},
{ 'key': '10.1016/j.phrs.2022.106360_bib58',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/nu13113951',
'article-title': 'l-Arginine and COVID-19: An Update',
'volume': '13',
'author': 'Adebayo',
'year': '2021',
'journal-title': 'Nutrients'},
{ 'key': '10.1016/j.phrs.2022.106360_bib59',
'doi-asserted-by': 'crossref',
'first-page': '935',
'DOI': '10.1016/j.jacbts.2021.09.013',
'article-title': 'Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A '
'Placebo-Controlled, Randomized Trial',
'volume': '6',
'author': 'Leucker',
'year': '2021',
'journal-title': 'JACC Basic Transl Sci'},
{ 'key': '10.1016/j.phrs.2022.106360_bib60',
'doi-asserted-by': 'crossref',
'first-page': '69',
'DOI': '10.1016/j.yjmcc.2021.11.010',
'article-title': 'Endothelial contribution to COVID-19: an update on mechanisms and '
'therapeutic implications',
'volume': '164',
'author': 'Ma',
'year': '2021',
'journal-title': 'J Mol Cell Cardiol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib61',
'doi-asserted-by': 'crossref',
'first-page': '451',
'DOI': '10.1186/s13063-021-05361-y',
'article-title': 'A randomized open-label trial to evaluate the efficacy and safety of '
'triple therapy with aspirin, atorvastatin, and nicorandil in '
'hospitalised patients with SARS Cov-2 infection: A structured summary '
'of a study protocol for a randomized controlled trial',
'volume': '22',
'author': 'Sharma',
'year': '2021',
'journal-title': 'Trials'},
{ 'key': '10.1016/j.phrs.2022.106360_bib62',
'doi-asserted-by': 'crossref',
'first-page': '589',
'DOI': '10.1007/s13337-021-00702-6',
'article-title': 'Assessment of nitric oxide (NO) potential to mitigate COVID-19 severity',
'volume': '32',
'author': 'Srivastava',
'year': '2021',
'journal-title': 'Virusdisease'},
{ 'key': '10.1016/j.phrs.2022.106360_bib63',
'doi-asserted-by': 'crossref',
'first-page': '33',
'DOI': '10.1111/andr.12837',
'article-title': 'Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection. The DEDALO '
'project',
'volume': '9',
'author': 'Isidori',
'year': '2021',
'journal-title': 'Andrology'},
{ 'issue': '2791S-2795S',
'key': '10.1016/j.phrs.2022.106360_bib64',
'first-page': '2796S',
'article-title': 'Renal arginine metabolism',
'volume': '134',
'author': 'Brosnan',
'year': '2004',
'journal-title': 'J Nutr'},
{ 'key': '10.1016/j.phrs.2022.106360_bib65',
'doi-asserted-by': 'crossref',
'first-page': '167',
'DOI': '10.1007/978-3-030-74180-8_10',
'article-title': 'Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans',
'volume': '1332',
'author': 'Wu',
'year': '2021',
'journal-title': 'Adv Exp Med Biol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib66',
'doi-asserted-by': 'crossref',
'first-page': '532',
'DOI': '10.3389/fimmu.2014.00532',
'article-title': 'Metabolism via Arginase or Nitric Oxide Synthase: Two Competing '
'Arginine Pathways in Macrophages',
'volume': '5',
'author': 'Rath',
'year': '2014',
'journal-title': 'Front Immunol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib67',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/biomedicines8080277',
'article-title': 'Arginine and Endothelial Function',
'volume': '8',
'author': 'Gambardella',
'year': '2020',
'journal-title': 'Biomedicines'},
{ 'key': '10.1016/j.phrs.2022.106360_bib68',
'doi-asserted-by': 'crossref',
'first-page': '521',
'DOI': '10.1016/S0008-6363(99)00115-7',
'article-title': 'Enzymatic function of nitric oxide synthases',
'volume': '43',
'author': 'Andrew',
'year': '1999',
'journal-title': 'Cardiovasc Res'},
{ 'key': '10.1016/j.phrs.2022.106360_bib69',
'first-page': '258',
'article-title': 'L-arginine-dependent nitric oxide synthase: a new metabolic pathway in '
'the lung and airways',
'volume': '6',
'author': 'Jorens',
'year': '1993',
'journal-title': 'Eur Respir J'},
{ 'key': '10.1016/j.phrs.2022.106360_bib70',
'doi-asserted-by': 'crossref',
'first-page': '4',
'DOI': '10.2174/157016112798829760',
'article-title': 'The role of nitric oxide on endothelial function',
'volume': '10',
'author': 'Tousoulis',
'year': '2012',
'journal-title': 'Curr Vasc Pharmacol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib71',
'doi-asserted-by': 'crossref',
'first-page': '1',
'DOI': '10.1016/j.jtbi.2016.01.009',
'article-title': 'The role of nitric oxide in neurovascular coupling',
'volume': '394',
'author': 'Dormanns',
'year': '2016',
'journal-title': 'J Theor Biol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib72',
'first-page': '515',
'article-title': '[L-Arginine and vascular health]',
'volume': '39',
'author': 'Ströhle',
'year': '2016',
'journal-title': 'Med Monatsschr Pharm'},
{ 'key': '10.1016/j.phrs.2022.106360_bib73',
'doi-asserted-by': 'crossref',
'first-page': '641',
'DOI': '10.1038/nri1668',
'article-title': 'Regulation of immune responses by L-arginine metabolism',
'volume': '5',
'author': 'Bronte',
'year': '2005',
'journal-title': 'Nat Rev Immunol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib74',
'doi-asserted-by': 'crossref',
'first-page': '1426',
'DOI': '10.3390/nu7031426',
'article-title': 'Arginine and citrulline and the immune response in sepsis',
'volume': '7',
'author': 'Wijnands',
'year': '2015',
'journal-title': 'Nutrients'},
{ 'key': '10.1016/j.phrs.2022.106360_bib75',
'article-title': 'Vitamin C and Cardiovascular Disease: An Update',
'volume': '9',
'author': 'Morelli',
'year': '2020',
'journal-title': 'Antioxidants (Basel)'},
{ 'key': '10.1016/j.phrs.2022.106360_bib76',
'article-title': 'Is Antioxidant Therapy a Useful Complementary Measure for Covid-19 '
'Treatment? An Algorithm for Its Application',
'author': 'Soto',
'year': '2020',
'journal-title': 'Medicina (Kaunas) 56, doi:10.3390/medicina56080386'},
{ 'key': '10.1016/j.phrs.2022.106360_bib77',
'doi-asserted-by': 'crossref',
'first-page': '1039',
'DOI': '10.1016/j.cell.2008.01.042',
'article-title': 'Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals '
'unable to synthesize vitamin C',
'volume': '132',
'author': 'Montel-Hagen',
'year': '2008',
'journal-title': 'Cell'},
{ 'key': '10.1016/j.phrs.2022.106360_bib78',
'doi-asserted-by': 'crossref',
'first-page': '13816',
'DOI': '10.1073/pnas.94.25.13816',
'article-title': 'Ascorbate recycling in human neutrophils: induction by bacteria',
'volume': '94',
'author': 'Wang',
'year': '1997',
'journal-title': 'Proc Natl Acad Sci U S A'},
{ 'key': '10.1016/j.phrs.2022.106360_bib79',
'doi-asserted-by': 'crossref',
'article-title': 'What is the role of supplementation with ascorbic acid, zinc, vitamin '
'D, or N-acetylcysteine for prevention or treatment of COVID-19?',
'author': 'Bauer',
'year': '2020',
'journal-title': 'Cleve Clin J Med',
'DOI': '10.3949/ccjm.87a.ccc046'},
{ 'key': '10.1016/j.phrs.2022.106360_bib80',
'doi-asserted-by': 'crossref',
'first-page': '1379',
'DOI': '10.1016/j.csbj.2021.02.009',
'article-title': 'Antioxidants and pentoxifylline as coadjuvant measures to standard '
'therapy to improve prognosis of patients with pneumonia by COVID-19',
'volume': '19',
'author': 'Chavarria',
'year': '2021',
'journal-title': 'Comput Struct Biotechnol J'},
{ 'key': '10.1016/j.phrs.2022.106360_bib81',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/nu12113286',
'article-title': 'The Emerging Role of Vitamin C in the Prevention and Treatment of '
'COVID-19',
'volume': '12',
'author': 'Carr',
'year': '2020',
'journal-title': 'Nutrients'},
{ 'key': '10.1016/j.phrs.2022.106360_bib82',
'doi-asserted-by': 'crossref',
'first-page': '676',
'DOI': '10.2119/molmed.2011.00103',
'article-title': 'Tetrahydrobiopterin, L-arginine and vitamin C act synergistically to '
'decrease oxidative stress, increase nitricoxide and improve blood flow '
'after induction of hindlimbischemia in the rat',
'volume': '18',
'author': 'Yan',
'year': '2012',
'journal-title': 'Mol Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib83',
'doi-asserted-by': 'crossref',
'first-page': '433',
'DOI': '10.1016/j.bbrc.2017.11.058',
'article-title': 'Ascorbic acid attenuates endothelial permeability triggered by '
'cell-free hemoglobin',
'volume': '495',
'author': 'Kuck',
'year': '2018',
'journal-title': 'Biochem Biophys Res Commun'},
{ 'key': '10.1016/j.phrs.2022.106360_bib84',
'doi-asserted-by': 'crossref',
'first-page': '1',
'DOI': '10.1016/j.mvr.2007.03.001',
'article-title': 'Effects of L-arginine on cerebral blood flow, microvascular '
'permeability, number of perfused capillaries, and brain water content '
'in the traumatized mouse brain',
'volume': '74',
'author': 'Lundblad',
'year': '2007',
'journal-title': 'Microvasc Res'},
{ 'key': '10.1016/j.phrs.2022.106360_bib85',
'doi-asserted-by': 'crossref',
'first-page': '701',
'DOI': '10.1016/j.bbrc.2010.12.046',
'article-title': 'Nitric oxide mediates tightening of the endothelial barrier by ascorbic '
'acid',
'volume': '404',
'author': 'May',
'year': '2011',
'journal-title': 'Biochem Biophys Res Commun'},
{ 'key': '10.1016/j.phrs.2022.106360_bib86',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/nu9111211',
'article-title': 'Vitamin C and Immune Function',
'volume': '9',
'author': 'Carr',
'year': '2017',
'journal-title': 'Nutrients'},
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'article-title': 'Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity '
'of Early Anticoagulation',
'volume': '12',
'author': 'Wang',
'year': '2022',
'journal-title': 'Front Cell Infect Microbiol'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3389/fcell.2022.824851',
'article-title': 'COVID-19 and the Vasculature: Current Aspects and Long-Term '
'Consequences',
'volume': '10',
'author': 'Martinez-Salazar',
'year': '2022',
'journal-title': 'Front Cell Dev Biol'},
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'doi-asserted-by': 'crossref',
'first-page': '626',
'DOI': '10.1038/s41591-021-01292-y',
'article-title': 'Attributes and predictors of long COVID',
'volume': '27',
'author': 'Sudre',
'year': '2021',
'journal-title': 'Nat Med'},
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'doi-asserted-by': 'crossref',
'article-title': 'L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical '
'Performance: New Insights for Managing Cardiovascular Patients During '
'the COVID-19 Pandemic',
'author': 'Mone',
'year': '2022',
'journal-title': 'J Pharmacol Exp Ther',
'DOI': '10.1124/jpet.122.001149'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3390/ijms21083004',
'article-title': 'RT-qPCR Testing of SARS-CoV-2: A Primer',
'volume': '21',
'author': 'Bustin',
'year': '2020',
'journal-title': 'Int J Mol Sci'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3390/jcm9051417',
'article-title': 'Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an '
'Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic '
'Evidence',
'volume': '9',
'author': 'Sardu',
'year': '2020',
'journal-title': 'J Clin Med'},
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'doi-asserted-by': 'crossref',
'first-page': '306',
'DOI': '10.1186/s13054-021-03731-1',
'article-title': 'Role of endothelial miR-24 in COVID-19 cerebrovascular events',
'volume': '25',
'author': 'Gambardella',
'year': '2021',
'journal-title': 'Crit Care'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3390/biomedicines10040812',
'article-title': 'Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a '
'Potential Therapeutic Target',
'volume': '10',
'author': 'Ambrosino',
'year': '2022',
'journal-title': 'Biomedicines'},
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'article-title': 'Exosomal miR-145 and miR-885 regulate thrombosis in COVID-19',
'author': 'Gambardella',
'year': '2022',
'journal-title': 'J Pharmacol Exp Ther',
'DOI': '10.1124/jpet.122.001209'},
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'doi-asserted-by': 'crossref',
'first-page': '155',
'DOI': '10.1016/j.ijcard.2021.11.051',
'article-title': 'Endothelial dysfunction in COVID-19: A potential predictor of '
'long-COVID',
'volume': '349',
'author': 'Seitz',
'year': '2022',
'journal-title': 'Int J Cardiol'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.vph.2022.106975',
'article-title': 'Endothelial dysfunction in acute and long standing COVID-19: A '
'prospective cohort study',
'volume': '144',
'author': 'Oikonomou',
'year': '2022',
'journal-title': 'Vascul Pharmacol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib98',
'first-page': '228',
'article-title': 'Circulating endothelial cells',
'volume': '93',
'author': 'Blann',
'year': '2005',
'journal-title': 'Biomarker of vascular disease. Thromb Haemost'},
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'doi-asserted-by': 'crossref',
'first-page': '1789',
'DOI': '10.1093/infdis/jiaa528',
'article-title': 'Circulating Endothelial Cells as a Marker of Endothelial Injury in '
'Severe COVID -19',
'volume': '222',
'author': 'Guervilly',
'year': '2020',
'journal-title': 'J Infect Dis'},
{ 'key': '10.1016/j.phrs.2022.106360_bib100',
'doi-asserted-by': 'crossref',
'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': '10.1016/j.phrs.2022.106360_bib101',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/v13112324',
'article-title': 'Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 '
'Patients: A Prospective Multicenter Study and Hypothesis',
'volume': '13',
'author': 'Vollenberg',
'year': '2021',
'journal-title': 'Viruses'},
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'doi-asserted-by': 'crossref',
'first-page': '2546',
'DOI': '10.1111/jth.15490',
'article-title': 'Persistent endotheliopathy in the pathogenesis of long COVID syndrome',
'volume': '19',
'author': 'Fogarty',
'year': '2021',
'journal-title': 'J Thromb Haemost'},
{ 'key': '10.1016/j.phrs.2022.106360_bib103',
'doi-asserted-by': 'crossref',
'DOI': '10.3389/fcvm.2021.745758',
'article-title': 'Long COVID 19 Syndrome: Is It Related to Microcirculation and '
'Endothelial Dysfunction? Insights From TUN-EndCOV Study',
'volume': '8',
'author': 'Charfeddine',
'year': '2021',
'journal-title': 'Front Cardiovasc Med'},
{ 'key': '10.1016/j.phrs.2022.106360_bib104',
'doi-asserted-by': 'crossref',
'first-page': '2251',
'DOI': '10.1001/jama.2020.22717',
'article-title': 'A Proposed Framework and Timeline of the Spectrum of Disease Due to '
'SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health '
'Implications',
'volume': '324',
'author': 'Datta',
'year': '2020',
'journal-title': 'JAMA'},
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'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.jclinane.2020.109926',
'article-title': 'Corticosteroids and the hyper-inflammatory phase of the COVID-19 '
'disease',
'volume': '66',
'author': 'Taboada',
'year': '2020',
'journal-title': 'J Clin Anesth'},
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'doi-asserted-by': 'crossref',
'first-page': '1441',
'DOI': '10.3389/fimmu.2020.01441',
'article-title': 'Immune Response, Inflammation, and the Clinical Spectrum of COVID-19',
'volume': '11',
'author': 'Garcia',
'year': '2020',
'journal-title': 'Front Immunol'},
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'doi-asserted-by': 'crossref',
'first-page': 'e594',
'DOI': '10.1016/S2665-9913(20)30275-7',
'article-title': 'COVID-19-associated hyperinflammation and escalation of patient care: a '
'retrospective longitudinal cohort study',
'volume': '2',
'author': 'Manson',
'year': '2020',
'journal-title': 'Lancet Rheumatol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib108',
'doi-asserted-by': 'crossref',
'first-page': '363',
'DOI': '10.1038/s41577-020-0311-8',
'article-title': 'The trinity of COVID-19: immunity, inflammation and intervention',
'volume': '20',
'author': 'Tay',
'year': '2020',
'journal-title': 'Nat Rev Immunol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib109',
'doi-asserted-by': 'crossref',
'DOI': '10.1172/JCI149412',
'article-title': 'Distinctive features of severe SARS-CoV-2 pneumonia',
'volume': '131',
'author': 'Budinger',
'year': '2021',
'journal-title': 'J Clin Invest'},
{ 'key': '10.1016/j.phrs.2022.106360_bib110',
'doi-asserted-by': 'crossref',
'first-page': '741',
'DOI': '10.1126/science.abe6522',
'article-title': 'Immunological characteristics govern the transition of COVID-19 to '
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'volume': '371',
'author': 'Lavine',
'year': '2021',
'journal-title': 'Science'},
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'doi-asserted-by': 'crossref',
'first-page': '228',
'DOI': '10.3389/fimmu.2013.00228',
'article-title': 'Arginase 1: an unexpected mediator of pulmonary capillary barrier '
'dysfunction in models of acute lung injury',
'volume': '4',
'author': 'Lucas',
'year': '2013',
'journal-title': 'Front Immunol'},
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'doi-asserted-by': 'crossref',
'first-page': '515',
'DOI': '10.1007/s10875-020-00920-5',
'article-title': 'SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte '
'Dysfunction, and Arginine Shortage',
'volume': '41',
'author': 'Reizine',
'year': '2021',
'journal-title': 'J Clin Immunol'},
{ 'key': '10.1016/j.phrs.2022.106360_bib113',
'article-title': 'Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor '
'Cells Determine their Association with Disease Severity of COVID-19',
'author': 'Dean',
'year': '2021',
'journal-title': 'medRxiv'},
{ 'key': '10.1016/j.phrs.2022.106360_bib114',
'doi-asserted-by': 'crossref',
'DOI': '10.3390/cells10082111',
'article-title': 'Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet '
'Activation by L-Arginine Deprivation during SARS-CoV-2 Infection',
'volume': '10',
'author': 'Sacchi',
'year': '2021',
'journal-title': 'Cells'},
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'doi-asserted-by': 'crossref',
'DOI': '10.3390/v14030534',
'article-title': 'Inducible Nitric Oxide Synthase (iNOS): Why a Different Production in '
'COVID-19 Patients of the Two Waves',
'volume': '14',
'author': 'Gelzo',
'year': '2022',
'journal-title': 'Viruses'},
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'doi-asserted-by': 'crossref',
'first-page': '2121',
'DOI': '10.1111/bph.15461',
'article-title': 'Dual inhibition of CB1 receptors and iNOS, as a potential novel '
'approach to the pharmacological management of acute and long COVID-19',
'volume': '179',
'author': 'Cinar',
'year': '2022',
'journal-title': 'Br J Pharmacol'},
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'doi-asserted-by': 'crossref',
'first-page': 'n1648',
'DOI': '10.1136/bmj.n1648',
'article-title': 'Long covid-mechanisms, risk factors, and management',
'volume': '374',
'author': 'Crook',
'year': '2021',
'journal-title': 'BMJ'},
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'doi-asserted-by': 'crossref',
'first-page': '631',
'DOI': '10.1007/s13365-020-00903-7',
'article-title': 'Neurological injuries in COVID-19 patients: direct viral invasion or a '
'bystander injury after infection of epithelial/endothelial cells',
'volume': '26',
'author': 'Azizi',
'year': '2020',
'journal-title': 'J Neurovirol'},
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'doi-asserted-by': 'crossref',
'first-page': '1473',
'DOI': '10.1080/07853890.2022.2076901',
'article-title': 'Pathophysiology and mechanism of long COVID: a comprehensive review',
'volume': '54',
'author': 'Castanares-Zapatero',
'year': '2022',
'journal-title': 'Ann Med'},
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'doi-asserted-by': 'crossref',
'first-page': '1745',
'DOI': '10.1038/s41467-022-29440-z',
'article-title': 'Neuropathology and virus in brain of SARS-CoV-2 infected non-human '
'primates',
'volume': '13',
'author': 'Rutkai',
'year': '2022',
'journal-title': 'Nat Commun'},
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'doi-asserted-by': 'crossref',
'article-title': 'Impaired exercise capacity in post-COVID syndrome: the role of '
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'author': 'Prasannan',
'year': '2022',
'journal-title': 'Blood Adv',
'DOI': '10.1182/bloodadvances.2021006944'},
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'doi-asserted-by': 'crossref',
'first-page': '7',
'DOI': '10.1186/1475-2891-11-7',
'article-title': 'Intravenous vitamin C administration reduces fatigue in office workers: '
'a double-blind randomized controlled trial',
'volume': '11',
'author': 'Suh',
'year': '2012',
'journal-title': 'Nutr J'},
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'doi-asserted-by': 'crossref',
'first-page': '139',
'DOI': '10.1007/s00280-013-2179-9',
'article-title': 'Phase I clinical trial to evaluate the safety, tolerability, and '
'pharmacokinetics of high-dose intravenous ascorbic acid in patients '
'with advanced cancer',
'volume': '72',
'author': 'Stephenson',
'year': '2013',
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'doi-asserted-by': 'crossref',
'first-page': '4104',
'DOI': '10.2337/dc13-0750',
'article-title': 'Vitamin C further improves the protective effect of glucagon-like '
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'and endothelial dysfunction in type 1 diabetes',
'volume': '36',
'author': 'Ceriello',
'year': '2013',
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'article-title': 'Combined effect of metformin with ascorbic acid versus acetyl salicylic '
'acid on diabetes-related cardiovascular complication; a 12-month single '
'blind multicenter randomized control trial',
'volume': '16',
'author': 'Gillani',
'year': '2017',
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