Subscribe to RSS
Perspectives on Platelet Heterogeneity and Host Immune Response in Coronavirus Disease 2019 (COVID-19)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.    As thrombocytopenia, systemic microvascular thrombosis, and elevated D-dimer levels reflect COVID-19 severity,    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.”  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.
03 September 2020 (online)
© 2020. Thieme. All rights reserved.
Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.
- 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