• P-ISSN 0974-6846 E-ISSN 0974-5645

Indian Journal of Science and Technology

Article

Pathogenesis and preventive approach of hypercoagulopathy and microvascular thrombosis induced mortality from COVID-19
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Indian Journal of Science and Technology

DOI: 10.17485/IJST/v13i30.969

Year: 2020, Volume: 13, Issue: 30, Pages: 3076-3087

Systematic Review

Pathogenesis and preventive approach of hypercoagulopathy and microvascular thrombosis induced mortality from COVID-19

Parthiba Pramanik1, Purushottam Pramanik2*

1Nil Ratan Sirkar Medical College and Hospital, West Bengal, Kolkatta, India
2Department of Zoology, Durgapur Government College, West Bengal, Durgapur, India

*Corresponding Author 
Email: [email protected]

Received Date:19 June 2020, Accepted Date:28 July 2020, Published Date:19 August 2020

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Background: COVID-19 is the current pandemic infection caused by severe acute respiratory syndrome coronavirus-2 (SARS Cov-2). Pulmonary collapse in severe critical COVID-19 patients may be due to development of multiple micro thrombi within pulmonary vasculature. As COVID-19 pandemic is accelerating, it is important to understand the molecular mechanism through which SARSCov2 induces hypercoagulopathy and intravascular thrombosis to be able to design more appropriate therapy. Focus of this review is to identify mechanisms through re-analysis of publicly available data by which SARS-Cov2 infection induce mortality by augmenting intravascular thrombosis and attempt to understand therapeutic approach to it. Findings: SARS Cov-2 accesses host cells via membrane bound angiotensin converting enzyme-2 (ACE2). This leads to imbalance of renin angiotensin system (RAS) increase ratio of Ag-II: Ag-1-7. Ag-II stimulates release of IP-10 from endothelium which upregulates local renin angiotensin system in endothelial cell by positive feedback process. Therefore it is suggested that angiotensin-II of renin angiotensin systemr in endothelial cells sustained proinflammatory signal and developed microvascular thrombosis. During inflammation both extrinsic and intrinsic coagulation pathways are activated. Fibrinolysis is suppressed by imbalance activity of two system: Ang-II-PAI-1 (plasminigen activator inhibitor-1) and Bradykinin-tPA (tissue plasminogen activator) system. Therapy with low molecular weight heparin (LMWH), which have anticoagulant and anti-inflammatory property, is associated with better prognostic in patients with severe COVID-19. ACE inhibitors decrease production of Ag-II and increases availability of bradykinin and consequence reduces coagulopathy Conclusion: Thus it is concluded that SARS-Cov2 infection induces microvascular thrombosis from hyperinflammation, misbalance between Ag-II and Ag-1-7 and imbalance activity of two system: Ang-II-PAI-1 and bradykinin-tPA system. ACE inhibitor and anticoagulant mainly LMWH and UFH may serve potential role in COVID-19 therapy particularly in patients with hypercoagulopathy and microvascular thrombosis.

Keywords: COVID19; angiotensin converting enzyme; renin angiotensin system; fibrinolysis; microvascular thrombosis; ACE inhibitor; heparin

References

  2. Corona virus Update . COVID-19 Virus Outbreak-Worldometer. (accessed ) Available from: https;//www.worldometers.nfo/coronavirus)www.worldometers.info
  3. Hui SD, Azhar IE, Madani AT, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China. International Journal of Infectious Diseases. 2020;91:264–266. Available from: https://dx.doi.org/10.1016/j.ijid.2020.01.009
  4. Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. GeroScience. 2020;42(2):505–514. Available from: https://dx.doi.org/10.1007/s11357-020-00186-0
  5. Rossi R, Coppi F, Talarico M, Boriani G. Protective role of chronic treatment with direct oral anticoagulants in elderly patients affected by interstitial pneumonia in COVID-19 era. European Journal of Internal Medicine. 2020;77:158–160. Available from: https://dx.doi.org/10.1016/j.ejim.2020.06.006
  9. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-Cov-2 infection. Clin Chem Lab Med. 2020. Available from: https://doi.org/10.1515/ccim-2020-0188
  11. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. Journal of Thrombosis and Haemostasis. 2020;18(5):1094–1099. Available from: https://dx.doi.org/10.1111/jth.14817
  13. Marietta M, Coluccio V, Luppi M. Covid-19, coagulopathy and venousembolism: more questions than answers. Int J Emergency Med. 2020. Available from: https://doi.org/10.1007/s11739-020-02432-x
  17. Atallah B, Mallah SI, AlMahmeed W. Anticoagulation in COVID-19. European Heart Journal - Cardiovascular Pharmacotherapy. 2020;6(4):260–261. Available from: https://dx.doi.org/10.1093/ehjcvp/pvaa036
  18. Klok FA, Kruip MJ, Meer NJVD, Arbous MS, Gommers DA, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020. Available from: https:doi.org/10.1016/j.thromres.2020.04.013
  19. Davidson S, Maini MK, Wack A. Disease-Promoting Effects of Type I Interferons in Viral, Bacterial, and Coinfections. Journal of Interferon & Cytokine Research. 2015;35(4):252–264. Available from: https://dx.doi.org/10.1089/jir.2014.0227
  20. Law KWH, Cheung CY, Ng HY, Sia SF, Chan YO, Luk W, et al. Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells. Blood. 2005;106(7):2366–2374. Available from: https://dx.doi.org/10.1182/blood-2004-10-4166
  22. Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogen and evidence based control and therapeutic strategies. Front Med. 2020;14(2):117–125.
  23. Messina F, Giombini E, Agrati C, Vairo F, Bartoli TA, Almoghazi S. COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS Cov-2 ifection. BMCJ Translational Medicine. 2020;18:233–242.
  24. Chen X, Yang X, Zheng Y, Yang Y, Sing Y, Chen Z. SARS coronavirus papine-like protease inhibits the type-1 interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell. 2014;5:369–381.
  25. Mirzaei R, Karampoor S, Sholeh M, Moradi P, Ranjbar R, Ghasemi F. A contemporary review on pathogenesis and immunity of COVID-19 infection. Molecular Biology Reports. 2020;47(7):5365–5376. Available from: https://dx.doi.org/10.1007/s11033-020-05621-1
  26. Channappanavar R, Fehr A, Vijay R, Mack M, Zhao J, Meyerholz D, et al. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host & Microbe. 2016;19(2):181–193. Available from: https://dx.doi.org/10.1016/j.chom.2016.01.007
  27. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020;395(10229):1033–1034. Available from: https://dx.doi.org/10.1016/s0140-6736(20)30628-0
  28. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clinical Rheumatology. 2020;39(7):2085–2094. Available from: https://dx.doi.org/10.1007/s10067-020-05190-5
  29. Wenham C, Smith J, Morgan R. COVID-19: the gendered impacts of the outbreak. The Lancet. 2020;395(10227):846–848. Available from: https://dx.doi.org/10.1016/s0140-6736(20)30526-2
  30. Souyris M, Cenac C, Azar P, Daviaud D, Canivet A, Grunenwald S, et al. TLR7escapes X chromosome inactivation in immune cells. Science Immunology. 2018;3(19):eaap8855. Available from: https://dx.doi.org/10.1126/sciimmunol.aap8855
  31. Berghofer B, Formmer T, Haley G. TLR7 ligands induce hgher IFN-alfa production in females. Journal of Immunology. 2006;177:2088–2096.
  32. Seillet C, Laffont S, Trémollières F, Rouquié N, Ribot C, Arnal JF, et al. The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling. Blood. 2012;119(2):454–464. Available from: https://dx.doi.org/10.1182/blood-2011-08-371831
  33. Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant changes of peripheral T-lymphocyte subsets in patients with severe acute respiratory syndrome. Journal of Infective Diseases. 2004;189(4):648–651.
  34. Wang X, Xu W, Hu G, Xia S, Sun Z, Liu Z, et al. Cov-2 infects T-lymphocytes through its spike protein mediated membrane fusion. Cellulau and molecular Immunology. 2020;5:1–3. Available from: https//:doi.org/10.1038/s41423-020-0424-9
  35. Li T, Qui Z, Han Y, Wang Z, Fan H, Lu W, et al. Rapid loss of both CD4+ and CD8+ T lymphocyte subsets during the acute phase of severe acute respiratory syndrome. Chinese Medical Journal. 2003;116(7):985–987.
  36. Chen J, Lau YF, Lamirande WE, Paddock CD, Bartlett JH, Zaki RS, et al. Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection. Journal of Virology. 2010;84(3):1289–1301. Available from: https://dx.doi.org/10.1128/jvi.01281-09
  37. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars in Immunopathology. 2017;39(5):529–539. Available from: https://dx.doi.org/10.1007/s00281-017-0629-x
  38. Daley-Bauer PL, Grace Wynn M, Mocarski SE. Cytomegalovirus Impairs Antiviral CD8+ T Cell Immunity by Recruiting Inflammatory Monocytes. Immunity. 2012;37(1):122–133. Available from: https://dx.doi.org/10.1016/j.immuni.2012.04.014
  39. Perrotta F, Matera MG, Cazzola M, Bianco A. Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Respiratory Medicine. 2020;168. Available from: https://dx.doi.org/10.1016/j.rmed.2020.105996
  40. Vaduganathan M, Vardeny O, Michel T, McMurray JVJ, Pfeffer AM, Solomon DS. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. New England Journal of Medicine. 2020;382(17):1653–1659. Available from: https://dx.doi.org/10.1056/nejmsr2005760
  42. Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. Journal of Internal Medicine. 2008;264(3):224–236. Available from: https://dx.doi.org/10.1111/j.1365-2796.2008.01981.x
  43. Tipnis SR, Hooper MM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting-enzyme. Cloning and functional expression as a captorpril-insensitive carboxypeptidase. Journal of Biological Chemistry. 2000;275:33238–33281.
  44. Gillian Rice I, Daniel Thomas A, Peter Grant J, Anthony Turner J, Nigel Hooper M. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochemical Journal. 2004;383(1):45–51. Available from: https://dx.doi.org/10.1042/bj20040634
  45. Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, et al. Tumor necrosis factor-alfa convertase (ADAM17) mediates regulated ectodomain shedding of the severe acute respiratory syndrome coronavirus (SARS-Cov) receptor, angiotensin converting enzyme2. Journal of Biological Chemistry. 2005;280:30113–30119.
  46. Sodhi PC, Wohlford-Lenane C, Yamaguchi Y, Prindle T, Fulton WB, Wang S, et al. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2018;314(1):L17–L31. Available from: https://dx.doi.org/10.1152/ajplung.00498.2016
  47. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCov infected patients linked to viral loads and lung injury. Science China Lifescience. 2020;63:364–374.
  48. Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. Angiotensin Converting enzyme-2 protect from lethal avian influenza: A H5N1 infection. Natural Communication. 2014;5:3594.
  49. Gu H, Xie Z, Li T, Zhang S, Lai C, Zhu P, et al. Angiotensin converting enzyme-2 inhibits lung injury induced by respiratory syncytial virus. Scientific Report. 2016;6.
  50. Dhochak N, Singhal T, Kabra SK, Lodha R. Pathophysiology of COVID-19: Why Children Fare Better than Adults? The Indian Journal of Pediatrics. 2020;87(7):537–546. Available from: https://dx.doi.org/10.1007/s12098-020-03322-y
  51. Gaertner F, Massberg S. Blood coagulation in immunothrombosis—At the frontline of intravascular immunity. Seminars in Immunology. 2016;28(6):561–569. Available from: https://dx.doi.org/10.1016/j.smim.2016.10.010
  53. Cao W, Li T. COVID-19: towards understanding of pathogenesis. Cell Res. 2020;30:367–369.
  55. Boccia M, Aronne L, Celia B, Mazzeo G, Ceparano M, D'Agnano V, et al. COVID-19 and coagulative axis: review of emerging aspects in a novel disease. Monaldi Archives for Chest Disease. 2020;90(2). Available from: https://dx.doi.org/10.4081/monaldi.2020.1300
  56. Keragala CB, Draxler DF, Mcquiltan ZK. Haemostasis and innate immunity: a review of the intricate relationship between coagulation and complement pathway. British Journal of Haematology. 2018;180:782–798.
  59. Colafrancesco S, Scrivo R, Barbati C, Conti F, Priori R. Targeting the Immune System for Pulmonary Inflammation and Cardiovascular Complications in COVID-19 Patients. Frontiers in Immunology. 2020;11. Available from: https://dx.doi.org/10.3389/fimmu.2020.01439
  61. Okajima K, Uchiba M, Murakami K, Okabe H, Takatsuki K. Plasma levels of soluble E-selectin in patients with disseminated intravascular coagulation. American Journal of Hematology. 1997;54(3):219–224. Available from: https://dx.doi.org/10.1002/(sici)1096-8652(199703)54:3<219::aid-ajh8>3.0.co;2-z
  63. Chua BHL, Chua CC, Diglio CA, Siu BB. Regulation of endothelin-1 mRNA by angiotensin II in rat heart endothelial cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1993;1178(2):201–206. Available from: https://dx.doi.org/10.1016/0167-4889(93)90010-m
  64. Halim A, Kanayama N, Maradny EE, Maehara K, Masahiko H, Terao T. Endothelin-1 increased immunoreactive von Willebrand factor in endothelial cells and induced micro thrombosis in rats. Thrombosis Research. 1994;76(1):71–78. Available from: https://dx.doi.org/10.1016/0049-3848(94)90208-9
  67. Sarma JV, Ward PA. The complement system. Cell and Tissue Research. 2011;343(1):227–235. Available from: https://dx.doi.org/10.1007/s00441-010-1034-0
  68. Kawecki C, Lenting PJ, Denis CV. Van Willibrand factor and inflammation. Journal of Thrombosis & Haemostasis. .
  69. Nakamura S, Nakamura I, Ma L, Vaughan DE, Fogo AB. Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo1. Kidney International. 2000;58(1):251–259. Available from: https://dx.doi.org/10.1046/j.1523-1755.2000.00160.x
  72. Brown JN, Nadeau HJ, Vaughan ED. Selective Stimulation of Tissue-Type Plasminogen Activator (t-PA) In Vivo by Infusion of Bradykinin. Thrombosis and Haemostasis. 1997;77(03):522–525. Available from: https://dx.doi.org/10.1055/s-0038-1656000
  73. Lippi G, South AM, Henry BM, Express A. Electrolyte imbalance in in patients with severe coronavirus disease-2019. Annal Clinical Biochemistry. 2020. Available from: https//:doi.org/10.1177/0004563220922255
  75. Sawathiparnich P, Kumar S, Vaughan ED, Brown JN. Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans. The Journal of Clinical Endocrinology & Metabolism. 2002;87(2):448–452. Available from: https://dx.doi.org/10.1210/jcem.87.2.7980
  76. Brown JN, Kim KS, Chen YQ, Blevins SL, Nadeau JH, Meranze GS, et al. Synergistic Effect of Adrenal Steroids and Angiotensin II on Plasminogen Activator Inhibitor-1 Production1. The Journal of Clinical Endocrinology & Metabolism. 2000;85(1):336–344. Available from: https://dx.doi.org/10.1210/jcem.85.1.6305
  77. Minai K, Matsumoto T, Horie H, Ohira N, Takashima H, Yokohama H, et al. Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors. Journal of the American College of Cardiology. 2001;37(6):1565–1570. Available from: https://dx.doi.org/10.1016/s0735-1097(01)01202-5
  78. Brown NJ, Baluta MM, Vintila MM. Plasminogen activator inhibitor-1 inhibition: another therapeutic option for cardiovascular protection. Medica. 2015;10(2):147–152.
  79. Baudin B, Berard M, Carrier JL, Legrand Y, Drouet L. Vascular Origin Determines Angiotensin I-Converting Enzyme Expression in Endothelial Cells. Endothelium. 1997;5(1):73–84. Available from: https://dx.doi.org/10.3109/10623329709044160
  80. Taddei S, Versari D, Cipriano A, Ghiadoni L, Galetta F, Franzoni F, et al. Identification of a Cytochrome P450 2C9-Derived Endothelium-Derived Hyperpolarizing Factor in Essential Hypertensive Patients. Journal of the American College of Cardiology. 2006;48(3):508–515. Available from: https://dx.doi.org/10.1016/j.jacc.2006.04.074
  81. Taddei S, Ghiadoni L, Virdis A, Versari D, Salvetti A. Mechanisms of Endothelial Dysfunction: Clinical Significance and Preventive Non-Pharmacological Therapeutic Strategies. Current Pharmaceutical Design. 2003;9(29):2385–2402. Available from: https://dx.doi.org/10.2174/1381612033453866
  82. Kossmann S, Hu H, Steven S, Schönfelder T, Fraccarollo D, Mikhed Y, et al. Inflammatory Monocytes Determine Endothelial Nitric-oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II. Journal of Biological Chemistry. 2014;289(40):27540–27550. Available from: https://dx.doi.org/10.1074/jbc.m114.604231
  84. Tamarat R, Silvestre JS, Durie M, Levy BI. Angiotensin II Angiogenic Effect In Vivo Involves Vascular Endothelial Growth Factor- and Inflammation-Related Pathways. Laboratory Investigation. 2002;82(6):747–756. Available from: https://dx.doi.org/10.1097/01.lab.0000017372.76297.eb
  85. Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Suzuki Y, Mazzano S, et al. Role of the renin angiotensin system in vascular disease: expanding the field. Hypertension. 2001;38:1382–1387.
  86. Chen XL, Tummala EP, Olbrych TM, Alexander RW, Medford MR. Angiotensin II Induces Monocyte Chemoattractant Protein-1 Gene Expression in Rat Vascular Smooth Muscle Cells. Circulation Research. 1998;83(9):952–959. Available from: https://dx.doi.org/10.1161/01.res.83.9.952
  87. Ide N, Hirase T, Nishimoto-Hazuku A, Ikeda Y, Node K. Angiotensin II Increases Expression of IP-10 and the Renin-Angiotensin System in Endothelial Cells. Hypertension Research. 2008;31(6):1257–1267. Available from: https://dx.doi.org/10.1291/hypres.31.1257
  88. Akishita M, Nagai K, Xi H, Yu W, Sudoh N, Watanabe T, et al. Renin-Angiotensin System Modulates Oxidative Stress–Induced Endothelial Cell Apoptosis in Rats. Hypertension. 2005;45(6):1188–1193. Available from: https://dx.doi.org/10.1161/01.hyp.0000165308.04703.f2
  89. Tomasian D. Antioxidants and the bioactivity of endothelium-derived nitric oxide. Cardiovascular Research. 2000;47(3):426–435. Available from: https://dx.doi.org/10.1016/s0008-6363(00)00103-6
  90. Luscher TF, Barton M. Biology of the endothelium. Clinical Cardiology. 1997;20:3–10.
  91. Zhang H, Penninger MJ, Li Y, Zhong N, Slutsky SA. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine. 2020;46(4):586–590. Available from: https://dx.doi.org/10.1007/s00134-020-05985-9
  92. Gupta N, Zhao YY, Evans CE. Stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77–83.
  93. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Rep Med. 2020;8:420–422.
  94. Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence. Journal of Clinical Medicine. 2020;9(5):1417. Available from: https://dx.doi.org/10.3390/jcm9051417
  95. Dzau JV. Tissue Angiotensin and Pathobiology of Vascular Disease. Hypertension. 2001;37(4):1047–1052. Available from: https://dx.doi.org/10.1161/01.hyp.37.4.1047
  96. Griendling KK, Lassegue B, Murphy TZ, Alexander RW. Angiotensin-II receptor pharmacology. Advance Pharmacology. 1994;28:269–306.
  97. Arenas AI, Xu Y, Lopez-Jaramillo P, Davidge TS. Angiotensin II-induced MMP-2 release from endothelial cells is mediated by TNF-α. American Journal of Physiology-Cell Physiology. 2004;286(4):C779–C784. Available from: https://dx.doi.org/10.1152/ajpcell.00398.2003
  98. Su JB, Houel R, Holoire F, Barde F, Beverelli F, Sambin L, et al. Stimulation of bradykinin B(1) receptor induces vasodilation in conductance and resistance coronary vessels in conscious dog: comparison with B(2) receptor stimulation. Circulation. 2000;101:1848–1853.
  99. Rahman MA, Murrow RJ, Ozkor AM, Kavtaradze N, Lin J, Staercke CD, et al. Endothelium-Derived Hyperpolarizing Factor Mediates Bradykinin-Stimulated Tissue Plasminogen Activator Release in Humans. Journal of Vascular Research. 2014;51(3):200–208. Available from: https://dx.doi.org/10.1159/000362666
  101. Ceconi C, Francolini G, Olivares A, Comini L, Bachetti T, Ferrari R. Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. European Journal of Pharmacology. 2007;577(1-3):1–6. Available from: https://dx.doi.org/10.1016/j.ejphar.2007.07.061
  103. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417–1418. Available from: https://dx.doi.org/10.1016/s0140-6736(20)30937-5
  104. Sato R, Ishikane M, Kinosita N, Suzuki T, Nakamoto T, Hayakawa K. A new challenge of unfractionated heparin anticoagulation treamen for moderate to severe COVID-19 I Japan. . Global Health & Medicine-Advance Publicaion. 2020. Available from: https:doi.org/10.35772/ghm-2020.01044
  105. Mucha SR, Dugar S, McCrae K, Joseph D, Bartholomew J, Sacha GL, et al. Coagulopathy in COVID-19: Manifestations and management. Cleveland Clinic Journal of Medicine. 2020;87(8):461–468. Available from: https://dx.doi.org/10.3949/ccjm.87a.ccc024
  106. Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thrombosis and Haemostasis. 2017;117(03):437–444. Available from: https://dx.doi.org/10.1160/th16-08-0620
  107. Lang J, Yang N, Deng J, Liu K, Yang P, Zhang G, et al. Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans. PLoS ONE. 2011;6(8):e23710. Available from: https://dx.doi.org/10.1371/journal.pone.0023710
  108. Mummery SR, Rider CC. Characterization of the Heparin-Binding Properties of IL-6. The Journal of Immunology. 2000;165(10):5671–5679. Available from: https://dx.doi.org/10.4049/jimmunol.165.10.5671
  109. Zhou F, Yu T, Du R, Fan G, Liu Y, Xiang J. Clinical course and risk factors for mortality of inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395(10229):1054–1062. Available from: https://doi.org/10.1016/S0140-6736(20)30566-3

Copyright

© 2020 Pramanik & Pramanik.This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Published By Indian Society for Education and Environment (iSee).

  • 25 August 2020

Year: 2020, Volume: 13, Issue: 30

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