Immuno-thrombosis, coagulopathy, pulmonary embolism and diagnosis in patients with COVID-19
Authors:
Miloš Dobiáš 2,3; Jan Lami 4; Lenka Bukovská 4; Josef Kořínek 1,2,3
Authors‘ workplace:
II. interní klinika - kardiologie a angiologie 1. LF UK a VFN v Praze
1; II. chirurgická klinika –kardiovaskulární chirurgie 1. LF UK a VFN v Praze
2; Klinika anesteziologie, resuscitace a intenzivní medicíny 1. LF UK a VFN v Praze
3; Centrum nukleární medicíny Bulovka, Praha
4
Published in:
AtheroRev 2022; 7(1): 6-13
Category:
Reviews
Overview
COVID-19 is associated with high risk of thrombosis development and pulmonary embolism (PE), that increases already significant mortality and morbidity in these patients. There are likely multiple mechanisms participating on the procoagulant status induced by the virus including dysregulation, excessive activation and dysfunction of coagulation cascade, fibrinolytic system, thrombocytes, endothelial cells and also dysregulation and excessive activation of some components of immune system which can affect hemostasis. This results in a coagulopathy associated with COVID-19 that is based on immuno- thrombotic factors. The review article also discusses diagnostic options for PE including D-dimers, CT pulmonary angiography and methods of nuclear medicine.
Keywords:
Pulmonary embolism – coagulopathy – COVID-19 – immuno-thrombosis
Sources
1. Osuchowski MF, Winkler MS, Tomasz Skirecki T et al. The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med 2021; 9(6): 622–642. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–2600(21)00218–6>.
2. Hanley B, Jensen M, Osborn M. Emerging spectrum of COVID-19-related cardiopulmonary pathology in adults. Diagn Histopathol (Oxf) 2021; 27(8): 317– 324. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mpdhp.2021.05.002>.
3. Williams A, Branscome H, Khatkar P et al. A comprehensive review of COVID-19 biology, diagnostics, therapeutics, and disease impacting the central nervous system. J Neurovirol 2021; 27(5): 667–690. Dostupné z DOI: <http://dx.doi.org/10.1007/s13365–021–00998–6>.
4. Ricci D, Etna MP, Rizzo F et al. Innate Immune Response to SARS-CoV-2 Infection: From Cells to Soluble Mediators. Int J Mol Sci 2021; 22(13): 7017. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms22137017>.
5. Alshammary AF, Al-Sulaiman AM. The journey of SARS-CoV-2 in human hosts: a review of immune responses, immunosuppression, and their consequences. Virulence 2021; 12(1): 1771–1794. Dostupné z DOI: <http://dx.doi.org/10.1080/21505594.2021.1929800>.
6. Sunkara H, Dewan SM. Coronavirus disease-2019: A review on the disease exacerbation via cytokine storm and concurrent management. Int Immunopharmacol 2021; 99: 108049. Dostupné z DOI: <http://dx.doi.org/10.1016/j.intimp.2021.108049>.
7. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 2020; 383(25): 2451–2460. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMcp2009575>.
8. Jamal M, Bangash HI, Habiba M et al. Immune dysregulation and system pathology in COVID-19. Virulence 2021; 12(1): 918–936. Dostupné z DOI: <http://dx.doi.org/10.1080/21505594.2021.1898790>.
9. Ackermann M, Verleden SE, Kuehnel M et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 2020; 383(2): 120–128. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2015432>.
10. Martinod K, Deppermann C. Immunothrombosis and thromboinflammation in host defense and disease. Platelets 2021; 32(3): 314–324. Dostupné z DOI: <http://dx.doi.org/10.1080/09537104.2020.1817360>.
11. O’Donnell JS, Peyvandi F, Martin-Loeches I. Pulmonary immuno-thrombosis in COVID-19 ARDS pathogenesis. Intensive Care Med 2021; 47(8): 899–902. Dostupné z DOI: <http://dx.doi.org/10.1007/s00134–021–06419-w>.
12. Coccheri S. COVID-19: The crucial role of blood coagulation and fibrinolysis. Intern Emerg Med 2020; 15(8): 1369–1373. Dostupné z DOI: <http://dx.doi.org/10.1007/s11739–020–02443–8>.
13. Bonaventura A, Vecchié A, Dagna L et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol 2021; 21(5): 319–329. Dostupné z DOI: <http://dx.doi.org/10.1038/s41577–021–00536–9>.
14. Siddiqi HK, Libby P, Ridker PM. COVID-19 – A vascular disease. Trends Cardiovasc Med 2021; 31(1): 1–5. Dostupné z DOI: <http://dx.doi.org/10.1016/j.tcm.2020.10.005>.
15. Allaoui A, Khawaja AA, Badad O et al. Platelet Function in Viral Immunity and SARS-CoV-2 Infection. Semin Thromb Hemost 2021; 47(4): 419–426. Dostupné z DOI: <http://dx.doi.org/10.1055/s-0041–1726033>.
16. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta 2020; 506: 145–148. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cca.2020.03.022>.
17. Zaid Y, Puhm F, Allaeys I et al. Platelets Can Associate With SARS-CoV-2 RNA and Are Hyperactivated in COVID-19. Circ Res 2020; 127(11): 1404–1418. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCRESAHA.120.317703>.
18. Pluta J, Cieniewicz A, Trzebicki J. COVID-19: coagulation disorders and anticoagulant treatment in patients hospitalised in ICU. Anaesthesiol Intensive Ther 2021; 53(2): 153–161. Dostupné z DOI: <http://dx.doi.org/10.5114/ait.2021.10578>.
19. Lax SF, Skok K, Zechner P et al. Pulmonary Arterial Thrombosis in COVID- 19 with Fatal Outcome: Results from a Prospective, Single-Center, Clinicopathologic Case Series. Ann Intern Med 2020; 173(5): 350–361. <http://dx.doi.org/10.7326/M20–2566>.
20. Abou-Ismail MY, Diamond A, Kapoor S et al. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res 2020; 194:101–115. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2020.06.029>.
21. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID- 2019 infection. Clin Chem Lab Med 2020; 58(7): 1131–1134. Dostupné z DOI: <http://dx.doi.org/10.1515/cclm-2020–0198>.
22. Jirak P, Larbig R, Shomanova Z et al. Myocardial injury in severe COVID‐19 is similar to pneumonias of other origin: results from a multicentre study. ESC Heart Fail 2021; 8(1): 37–46. Dostupné z DOI: <http://dx.doi.org/10.1002/ehf2.13136>.
23. Steadman E, Fandaros M, Yin W. SARS-CoV-2 and Plasma Hypercoagulability. Cell Mol Bioeng 2021; 14(5): 1–10. Dostupné z DOI: <http://dx.doi.org/10.1007/s12195–021–00685-w>.
24. Fard MB, Fard SB, Ramazi S et al. Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity. Thromb J 2021; 19(1): 59. Dostupné z DOI: <http://dx.doi.org/10.1186/s12959–021–00311–9>.
25. Krüger G, Blocki A, Franke RP et al. Vascular Endothelial Cell Biology: An Update. Int J Mol Sci 2019; 20(18): 4411. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms20184411>.
26. Sturtzel C. Endothelial Cells. Adv Exp Med Biol 2017; 1003: 71–91. Dostupné z DOI: <http://dx.doi.org/10.1007/978–3-319–57613–8_4>.
27. Teijaro JR, Walsh KB, Cahalan S et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146(6): 980–991. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cell.2011.08.015>.
28. Tay MZ, Poh CM, Rénia L et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; 20(6): 363–374. Dostupné z DOI: <http://dx.doi.org/10.1038/s41577–020–0311–8>.
29. Galati D, Zanotta S, Capitelli L et al. A bird's eye view on the role of dendritic cells in SARS‐CoV‐2 infection: Perspectives for immune‐based vaccines. Allergy 2022; 77(1): 100–110. Dostupné z DOI: <http://dx.doi.org/10.1111/all.15004>.
30. Otsuka R, Seino KI. Macrophage activation syndrome and COVID-19. Inflamm Regen 2020; 40: 19. Dostupné z DOI: <http://dx.doi.org/10.1186/s41232–020–00131-w>.
31. Cui SN, Tan HY, Fan GC. Immunopathological Roles of Neutrophils in Virus Infection and COVID-19. Shock 2021; 56(3): 345–351. Dostupné z DOI: <http://dx.doi.org/10.1097/SHK.0000000000001740>.
32. Björkström NK, Ponzetta A. Natural killer cells and unconventional T cells in COVID-19. Curr Opin Virol 2021; 49: 176–182. Dostupné z DOI: <http://dx.doi.org/10.1016/j.coviro.2021.06.005>.
33. Zanoni I. Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19? Curr Opin Virol 2021; 50: 119–127. Dostupné z DOI: <http://dx.doi.org/10.1016/j.coviro.2021.08.004>.
34. Land WG. Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome—with a preliminary reference to SARS-CoV-2 pneumonia. Genes Immun 2021; 22(3): 141–160. Dostupné z DOI: <http://dx.doi.org/10.1038/s41435–021–00140-w>.
35. Skendros P, Mitsios A, Chrysanthopoulou A et al. Complement and tissue factor–enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest 2020; 130(11): 6151–6157. Dostupné z DOI: <http://dx.doi.org/10.1172/JCI141374>.
36. Liu X, Zhang R, He G. Hematological findings in coronavirus disease 2019: indications of progression of disease. Ann Hematol 2020; 99(7): 1421–1428. Dostupné z DOI: <http://dx.doi.org/10.1007/s00277–020–04103–5>.
37. McNab F, Mayer-Barber K, Sher A et al. Type I interferons in infectious disease. Nat Rev Immunol 2015; 15(2): 87–103. Dostupné z DOI: <http://dx.doi.org/10.1038/nri3787>.
38. Zhang D, Guo R, Lei L et al. Frontline Science: COVID‐19 infection induces readily detectable morphologic and inflammation‐related phenotypic changes in peripheral blood monocytes. J Leukoc Biol 2021; 109(1): 13–22. Dostupné z DOI: <http://dx.doi.org/10.1002/JLB.4HI0720–470R>.
39. Acharya D, Liu G, Gack MU. Dysregulation of type I interferon responses in COVID-19. Nat Rev Immunol 2020; 20(7): 397–398. Dostupné z DOI: <http://dx.doi.org/10.1038/s41577–020–0346-x>.
40. Jaillon S, Galdiero MS, Del Prete D et al. Neutrophils in innate and adaptive immunity. Semin Immunopathol
41. 2013; 35(4): 377–394. Dostupné z DOI: <http://dx.doi.org/10.1007/s00281–013–0374–8>.
42. Bonaventura A, Liberale L, Carbone F et al. The Pathophysiological Role of Neutrophil Extracellular Traps in Inflammatory Diseases. Thromb Haemost 2018; 118(1): 6–27. <http://dx.doi.org/10.1160/TH17–09–0630>.
43. Malech HL. The role of neutrophils in the immune system: an overview. Methods Mol Biol 2007; 412: 3–11. Dostupné z DOI: <http://dx.doi.org/10.1007/978–1-59745–467–4_1>.
44. Wang D, Hu B, Hu C et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061–1069. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2020.1585>.
45. Zuo Y, Zuo M, Yalavarthi S et al. Neutrophil extracellular traps and thrombosis in COVID-19. J Thromb Thrombolysis 2021; 51(2): 446–453. Dostupné z DOI: <http://dx.doi.org/10.1007/s11239–020–02324-z>.
46. Middleton EA, He XY, Denorme F et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 2020; 136(10): 1169–1179. Dostupné z DOI: <http://dx.doi.org/10.1182/blood.2020007008>.
47. Risitano AM, Mastellos DC, Huber-Lang M et al. Complement as a target in COVID-19? Nat Rev Immunol 2020; 20(6): 343–344. Dostupné z DOI: <http://dx.doi.org/10.1038/s41577–020–0320–7>.
48. Gao T, Hu M, Zhang X et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation. MedRxiv 2020. Dostupné z WWW: <https://www.medrxiv.org/content/medrxiv/early/2020/03/30/2020.03.29.20041962.full.pdf>.
49. Afshar-Kharghan V. Complement and clot. Blood 2017; 129(16): 2214– 2215. . Dostupné z DOI: <http://dx.doi.org/10.1182/blood-2017–03–771501>.
50. Obi AT, Barnes GD, Napolitano LM et al. Venous thrombosis epidemiology, pathophysiology, and anticoagulant therapies and trials in severe acute respiratory syndrome coronavirus 2 infection. J Vasc Surg Venous Lymphat Disord 2021; 9(1): 23–35. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jvsv.2020.08.030>.
51. Klok FA, Kruip MJ, van der Meer NJ et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191: 145– 147. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2020.04.013>.
52. Helms J, Tacquard C, Severac F et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020; 46(6): 1089–1098. Dostupné z DOI: <http://dx.doi.org/10.1007/s00134–020–06062-x>.
53. Guagliumi G, Sonzogni A, Pescetelli I et al. Microthrombi and ST-Segment- Elevation Myocardial Infarction in COVID-19. Circulation 2020; 142(8): 804–809. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049294A>.
54. Pellegrini D, Kawakami R, Guagliumi G et al. Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study. Circulation 2021; 143(10): 1031–1042. Dostupné z DOI: <http://10.1161/CIRCULATIONAHA.120.051828>.
55. Remy-Jardin M, Duthoit L, Perez T et al. Assessment of pulmonary arterial circulation 3 months after hospitalization for SARS-CoV-2 pneumonia: Dual-energy CT (DECT) angiographic study in 55 patients. EClinicalMedicine 2021; 34: 100778. Dostupné z DOI: <http://dx.doi.org/10.1016/j.eclinm.2021.100778>.
56. Pavli A, Theodoridou, Maltezou HC. Post-COVID Syndrome: Incidence, Clinical Spectrum, and Challenges for Primary Healthcare Professionals. Arch Med Res 2021; 52(6): 575–581. Dostupné z DOI: <http://dx.doi.org/10.1016/j.arcmed.2021.03.010>.
57. Ali MA, Spinler SA. COVID-19 and thrombosis: From bench to bedside. Trends Cardiovasc Med 2021; 31(3): 143–160. Dostupné z DOI: <http://dx.doi.org/10.1016/j.arcmed.2021.03.010>.
58. Rosovsky RP, Grodzin C, Channick R et al. Diagnosis and Treatment of Pulmonary Embolism during the Coronavirus Disease 2019 Pandemic. Chest 2020; 158(6): 2590–2601.Dostupné z DOI: <http://dx.doi.org/10.1016/j.chest.2020.08.2064>.
59. Konstantinides SV, Meyer G, Becattini C et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J 2019; 54(3): 1901647. Dostupné z DOI:<http://dx.doi.org/10.1183/13993003.01647–2019>.
60. van Dam LF, Kroft LJ, van der Wal LI, et al. Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease? Thromb Res 2020; 193:86–89. Dostupné z DOI: <http://dx.doi.org/10.1016/j.thromres.2020.06.010>.
61. Kollias A, Kyriakoulis KG, Dimakakos E et al. Thromboembolic risk and anticoagulant therapy in COVID‐19 patients: emerging evidence and call for action. Br J Haematol 2020; 189(5): 846–847. Dostupné z DOI: <http://dx.doi.org/10.1111/bjh.16727>.
62. Trunz LM, Lee P, Lange SM et al. Imaging approach to COVID-19 associated pulmonary embolism. Int J Clin Pract 2021 Oct; 75(10): e14340. Dostupné z DOI: <http://dx.doi.org/10.1111/ijcp.14340>.
63. Lu Y, Macapinlac HA. Perfusion SPECT/CT to diagnose pulmonary embolism during COVID-19 pandemic. Eur J Nucl Med Mol Imaging 2020; 47(9): 2064–2065. Dostupné z DOI: <http://dx.doi.org/10.1007/s00259–020–04851–6>.
64. Dhawan RT, Gopalan D, Howard L et al. Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19. Lancet Respir Med 2021; 9(1): 107–116. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–2600(20)30407–0>.
65. Marconi L, Palla A, Cestelli L et al. Should Perfusion Scintigraphy Be Performed to Follow Patients with Acute Pulmonary Embolism? If So, When? J Nucl Med 2019; 60(8): 1134–1139. Dostupné z DOI: <http://dx.doi.org/10.2967/jnumed.118.222737>.
66. Meneveau N, Ider O, Seronde MF et al. Long-term prognostic value of residual pulmonary vascular obstruction at discharge in patients with intermediate- to high-risk pulmonary embolism. Eur Heart J 2013; 34(9): 693–701. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehs36>.
67. Patel BV, Arachchillage DJ, Ridge CA et al. Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations. Am J Respir Crit Care Med 2020; 202(5): 690–699. Dostupné z DOI: <http://dx.doi.org/10.1164/rccm.202004–1412OC>.
68. Carrier M, Righini M, Wells PS et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost 2010; 8(8): 1716–1722. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1538–7836.2010.03938.x>.
69. Cavagna E, Muratore F, Ferrari F. Pulmonary Thromboembolism in COVID- 19: Venous Thromboembolism or Arterial Thrombosis? Radiol Cardiothorac Imaging 2020; 2(4): e200289. Dostupné z DOI: <http://dx.doi.org/10.1148/ryct.2020200289>.
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2022 Issue 1
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