Semin Thromb Hemost 2020; 46(07): 826-830
DOI: 10.1055/s-0040-1715093
Commentary

Perspectives on Platelet Heterogeneity and Host Immune Response in Coronavirus Disease 2019 (COVID-19)

Iván Parra-Izquierdo
1   Knight Cardiovascular Institute, Division of Cardiology, Department of Medicine, School of Medicine, Oregon Health and Science University, Portland, Oregon
2   Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon
,
Joseph E. Aslan
1   Knight Cardiovascular Institute, Division of Cardiology, Department of Medicine, School of Medicine, Oregon Health and Science University, Portland, Oregon
2   Department of Biomedical Engineering, School of Medicine, Oregon Health and Science University, Portland, Oregon
3   Department of Chemical Physiology and Biochemistry, School of Medicine, Oregon Health and Science University, Portland, Oregon
› Author Affiliations
Funding This work is supported by the National Institutes of Health (grant R01HL146549).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) represent a global pandemic with largely uncharacterized but dire public health consequences. COVID-19 is now increasingly recognized as a thromboinflammatory disease, where thrombotic coagulopathy and intravascular coagulation are closely linked to mortality and clinical outcomes.[1] [2] [3] [4] As thrombocytopenia, systemic microvascular thrombosis, and elevated D-dimer levels reflect COVID-19 severity,[1] [2] [3] [4] cellular effectors of hemostasis and thrombosis—especially platelets—likely participate in COVID-19 pathogenesis. However, specific roles for platelets in COVID-19 as disease drivers, biomarkers, and therapeutic targets remain unspecified. Here, we highlight how platelets may be affected by COVID-19 in a manner supporting pathology, which offers insights into COVID-19 susceptibility, progression, and resolution. Like other viral infections and inflammatory states, COVID-19 likely involves alterations in platelet number, form, and function, or “platelet heterogeneity.”[5] [6] Knowledge gained over the past decade detailing mechanisms of platelet heterogeneity in inflammation and immune responses may help to gain ground in the battle against COVID-19. In turn, a surge of collaborative studies around COVID-19 pathogenesis may result in unique insights into platelet function critical to understanding and managing other inflammatory disease states.



Publication History

Article published online:
03 September 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 
  • References

  • 1 Larsen JB, Pasalic L, Hvas AM. Platelets in coronavirus disease 2019. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1710006.
  • 2 Al-Samkari H, Karp Leaf RS, Dzik WH. et al. COVID and coagulation: bleeding and thrombotic manifestations of SARS-CoV2 infection. Blood 2020; (e-pub ahead of print) DOI: 10.1182/blood.2020006520.
  • 3 Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med 2020; (e-pub ahead of print) DOI: 10.1016/S2213-2600(20)30243-5.
  • 4 Chen G, Wu D, Guo W. et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130 (05) 2620-2629
  • 5 Baaten CCFMJ, Ten Cate H, van der Meijden PEJ, Heemskerk JWM. Platelet populations and priming in hematological diseases. Blood Rev 2017; 31 (06) 389-399
  • 6 van der Meijden PEJ, Heemskerk JWM. Platelet biology and functions: new concepts and clinical perspectives. Nat Rev Cardiol 2019; 16 (03) 166-179
  • 7 Aslan JE. Platelet shape change. In: Gresele P, López J, Kleiman N, Page C. eds, Platelets in Thrombotic and Non-Thrombotic Disorders. Cham, Switzerland: Springer; 2017
  • 8 Berger JS, Becker RC, Kuhn C, Helms MJ, Ortel TL, Williams R. Hyperreactive platelet phenotypes: relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation. Thromb Haemost 2013; 109 (01) 85-92
  • 9 Agbani EO, Poole AW. Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis. Blood 2017; 130 (20) 2171-2179
  • 10 Munnix IC, Cosemans JM, Auger JM, Heemskerk JW. Platelet response heterogeneity in thrombus formation. Thromb Haemost 2009; 102 (06) 1149-1156
  • 11 Koupenova M, Vitseva O, MacKay CR. et al. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood 2014; 124 (05) 791-802
  • 12 Koupenova M, Clancy L, Corkrey HA, Freedman JE. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ Res 2018; 122 (02) 337-351
  • 13 Katz JN, Kolappa KP, Becker RC. Beyond thrombosis: the versatile platelet in critical illness. Chest 2011; 139 (03) 658-668
  • 14 Page MJ, Pretorius E. A champion of host defense: a generic large-scale cause for platelet dysfunction and depletion in infection. Semin Thromb Hemost 2020; 46 (03) 302-319
  • 15 D' Atri LP, Schattner M. Platelet toll-like receptors in thromboinflammation. Front Biosci 2017; 22: 1867-1883
  • 16 Assinger A, Kral JB, Yaiw KC. et al. Human cytomegalovirus-platelet interaction triggers toll-like receptor 2-dependent proinflammatory and proangiogenic responses. Arterioscler Thromb Vasc Biol 2014; 34 (04) 801-809
  • 17 Quirino-Teixeira AC, Rozini SV, Barbosa-Lima G. et al. Inflammatory signaling in dengue-infected platelets requires translation and secretion of nonstructural protein 1. Blood Adv 2020; 4 (09) 2018-2031
  • 18 Manne BK, Denorme F, Middleton EA. et al. Platelet gene expression and function in COVID-19 patients. Blood 2020; DOI: 10.1182/blood.2020007214. [epub ahead of print]
  • 19 Koupenova M. Potential role of platelets in COVID-19: implications for thrombosis. research and practice in thrombosis and haemostasis. Res Pract Thromb Haemost 2020; 4 (05) 737-740
  • 20 Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog 2020; 16 (05) e1008536
  • 21 Houck KL, Yuan H, Tian Y. et al. Physical proximity and functional cooperation of glycoprotein 130 and glycoprotein VI in platelet membrane lipid rafts. J Thromb Haemost 2019; 17 (09) 1500-1510
  • 22 Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol 2020; 20 (06) 355-362
  • 23 Xu X, Han M, Li T. et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020; 117 (20) 10970-10975
  • 24 Hottz ED, Azevedo-Quintanilha IG, Palhinha L. et al. Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients. Blood 2020; DOI: 10.1182/blood.2020007252. [epub ahead of print]
  • 25 Middleton EA, He XY, Denorme F. et al. neutrophil extracellular traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020; . (epub ahead of print) DOI: 10.1182/blood.2020007008.
  • 26 Shen B, Yi X, Sun Y. et al. Proteomic and metabolomic characterization of COVID-19 Patient Sera. Cell 2020; (e-pub ahead of print) DOI: 10.1016/j.cell.2020.05.032.
  • 27 Messner CB, Demichev V, Wendisch D. et al. Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection. Cell Syst 2020; (e-pub ahead of print) DOI: 10.1016/j.cels.2020.05.012.
  • 28 Magro C, Mulvey JJ, Berlin D. et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 2020; 220: 1-13
  • 29 Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int 2020; (e-pub ahead of print) DOI: 10.1016/j.kint.2020.05.013.
  • 30 Eriksson O, Mohlin C, Nilsson B, Ekdahl KN. The human platelet as an innate immune cell: interactions between activated platelets and the complement system. Front Immunol 2019; 10: 1590
  • 31 Qiu J, Ma J, Zhang S, Han J, Liu S. Promoting platelets is a therapeutic option to combat severe viral infection of the lung. Blood Adv 2020; 4 (08) 1640-1642
  • 32 Bomhof G, Mutsaers PGNJ, Leebeek FWG. et al. COVID-19-associated immune thrombocytopenia. Br J Haematol 2020; (e-pub ahead of print) DOI: 10.1111/bjh.16850.
  • 33 Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020; 99 (06) 1205-1208
  • 34 Matacic C. Blood vessel injury may spur disease's fatal second phase. Science 2020; 368 (6495): 1039-1040
  • 35 Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol 2020; (e-pub ahead of print) DOI: 10.1038/s41577-020-0343-0.
  • 36 Chen J, Chung DW. Inflammation, von Willebrand factor, and ADAMTS13. Blood 2018; 132 (02) 141-147
  • 37 Panigada M, Bottino N, Tagliabue P. et al. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost 2020; (e-pub ahead of print) DOI: 10.1111/jth.14850.
  • 38 Helms J, Tacquard C, Severac F. et al; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 2020; 46: 1089-1098
  • 39 Rayes J, Watson SP, Nieswandt B. Functional significance of the platelet immune receptors GPVI and CLEC-2. J Clin Invest 2019; 129 (01) 12-23
  • 40 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115 (12) 3378-3384
  • 41 Bikdeli B, Madhavan MV, Gupta A. et al; Global COVID-19 Thrombosis Collaborative Group. Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research. Thromb Haemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1713152.
  • 42 Liu X, Li Z, Liu S. et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020; (e-pub ahead of print) DOI: 10.1016/j.apsb.2020.04.008.
  • 43 Russo V, Di Maio M, Attena E. et al. Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: a multicenter observational study. Pharmacol Res 2020; 159: 104965
  • 44 Libby P. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J Am Coll Cardiol 2017; 70 (18) 2278-2289
  • 45 Roschewski M, Lionakis MS, Sharman JP. et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol 2020; 5 (48) eabd0110
  • 46 Treon SP, Castillo JJ, Skarbnik AP. et al. The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19-infected patients. Blood 2020; 135 (21) 1912-1915
  • 47 Shatzel JJ, DeLoughery EP, Lorentz CU. et al. The contact activation system as a potential therapeutic target in patients with COVID-19. Res Pract Thromb Haemost 2020; 4 (04) 500-505
  • 48 Zhu L, She ZG, Cheng X. et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab 2020; 31 (06) 1068-1077
  • 49 Parra-Izquierdo I, Bradley R, Aslan JE. Platelets get gutted by PAG. Platelets 2020; 1–3: 1-3
  • 50 Gupta AK, Jneid H, Addison D. et al. Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors. J Am Heart Assoc 2020; 9 (12) e017013
  • 51 Babur Ö, Melrose AR, Cunliffe JM. et al. Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs. Blood 2020; DOI: 10.1182/blood.2020005496. [epub ahead of print]
  • 52 Ostaszewski M, Mazein A, Gillespie ME. et al. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms. Sci Data 2020; 7 (01) 136