Abstract
Introduction: Thromboembolic events are one of the important complications in COVID-19 patients, especially in severe cases. Aspirin affects platelet function by irreversibly inhibiting cyclooxygenase activity, reducing the risk of thrombosis. The current systematic review aimed to evaluate aspirin's effectiveness in preventing pro-thrombotic states in COVID-19 hospitalized patients.
Methods: The systematic search was done in PubMed/Medline, EMBASE, and Medrxiv until September 27, 2021. The following keywords were used: “COVID-19”, “SARS-CoV-2”, “2019 Novel Coronavirus”, “Aspirin,” and “Acetylsalicylic Acid.”
Results: Twelve studies were included. In COVID-19 patients, aspirin can reduce CRP, IL-6 levels, and platelet aggregation by inhibiting thromboxane A2. It can also improve antiviral immunity by hindering the biosynthesis of prostaglandins and lipoxin. Eight out of twelve articles indicated that aspirin provided a beneficial effect on COVID-19. Most studies consider lowered mechanical ventilation needs, ICU admission, illness severity, overt thrombosis, and clinical outcomes in COVID-19 patients receiving aspirin.
Conclusion: Aspirin as an antiplatelet and anti-inflammatory agent may reduce the mortality rates in hospitalized patients with severe COVID-19. Further observational studies are necessary to determine the effect of aspirin on the prevention of pro-thrombotic states in hospitalized COVID- 19 patients.
Keywords: Aspirin, acetylsalicylic acid, thrombosis, SARS-COV-2, COVID-19, pro-thrombotic.
[1]
Shi, Y.; Wang, G.; Cai, X.P.; Deng, J.W.; Zheng, L.; Zhu, H.H.; Zheng, M.; Yang, B.; Chen, Z. An overview of COVID-19. J. Zhejiang Univ. Sci. B, 2020, 21(5), 343-360.
[http://dx.doi.org/10.1631/jzus.B2000083] [PMID: 32425000]
[http://dx.doi.org/10.1631/jzus.B2000083] [PMID: 32425000]
[2]
Organization WH. WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February 2020. 2020.
[3]
Pascarella, G.; Strumia, A.; Piliego, C.; Bruno, F.; Del Buono, R.; Costa, F.; Scarlata, S.; Agrò, F.E. COVID-19 diagnosis and management: A comprehensive review. J. Intern. Med., 2020, 288(2), 192-206.
[http://dx.doi.org/10.1111/joim.13091] [PMID: 32348588]
[http://dx.doi.org/10.1111/joim.13091] [PMID: 32348588]
[4]
Organization WH. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. 2020.
[5]
Kordzadeh-Kermani, E.; Khalili, H.; Karimzadeh, I. Pathogenesis, clinical manifestations and complications of coronavirus disease 2019 (COVID-19). Future Microbiol., 2020, 15, 1287-1305.
[http://dx.doi.org/10.2217/fmb-2020-0110] [PMID: 32851877]
[http://dx.doi.org/10.2217/fmb-2020-0110] [PMID: 32851877]
[6]
Bilaloglu, S.; Aphinyanaphongs, Y.; Jones, S.; Iturrate, E.; Hochman, J.; Berger, J.S. Thrombosis in hospitalized patients with COVID-19 in a New York City health system. JAMA, 2020, 324(8), 799-801.
[http://dx.doi.org/10.1001/jama.2020.13372] [PMID: 32702090]
[http://dx.doi.org/10.1001/jama.2020.13372] [PMID: 32702090]
[7]
Lodigiani, C.; Iapichino, G.; Carenzo, L.; Cecconi, M.; Ferrazzi, P.; Sebastian, T.; Kucher, N.; Studt, J.D.; Sacco, C.; Bertuzzi, A.; Sandri, M.T.; Barco, S. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb. Res., 2020, 191, 9-14.
[http://dx.doi.org/10.1016/j.thromres.2020.04.024] [PMID: 32353746]
[http://dx.doi.org/10.1016/j.thromres.2020.04.024] [PMID: 32353746]
[8]
Wichmann, D.; Sperhake, J.P.; Lütgehetmann, M.; Steurer, S.; Edler, C.; Heinemann, A.; Heinrich, F.; Mushumba, H.; Kniep, I.; Schröder, A.S.; Burdelski, C.; de Heer, G.; Nierhaus, A.; Frings, D.; Pfefferle, S.; Becker, H.; Bredereke-Wiedling, H.; de Weerth, A.; Paschen, H.R.; Sheikhzadeh-Eggers, S.; Stang, A.; Schmiedel, S.; Bokemeyer, C.; Addo, M.M.; Aepfelbacher, M.; Püschel, K.; Kluge, S. Autopsy findings and venous thromboembolism in patients with COVID-19: A prospective cohort study. Ann. Intern. Med., 2020, 173(4), 268-277.
[http://dx.doi.org/10.7326/M20-2003] [PMID: 32374815]
[http://dx.doi.org/10.7326/M20-2003] [PMID: 32374815]
[9]
Mohamed-Hussein, A.A.R.; Aly, K.M.E.; Ibrahim, M.A.A. Should aspirin be used for prophylaxis of COVID-19-induced coagulopathy? Med. Hypotheses, 2020, 144, 109975.
[http://dx.doi.org/10.1016/j.mehy.2020.109975] [PMID: 32531536]
[http://dx.doi.org/10.1016/j.mehy.2020.109975] [PMID: 32531536]
[10]
Baigent, C.; Blackwell, L.; Collins, R.; Emberson, J.; Godwin, J.; Peto, R.; Buring, J.; Hennekens, C.; Kearney, P.; Meade, T.; Patrono, C.; Roncaglioni, M.C.; Zanchetti, A. Aspirin in the primary and secondary prevention of vascular disease: Collaborative meta-analysis of in-dividual participant data from randomised trials. Lancet, 2009, 373(9678), 1849-1860.
[http://dx.doi.org/10.1016/S0140-6736(09)60503-1] [PMID: 19482214]
[http://dx.doi.org/10.1016/S0140-6736(09)60503-1] [PMID: 19482214]
[11]
Simes, J.; Becattini, C.; Agnelli, G.; Eikelboom, J.W.; Kirby, A.C.; Mister, R.; Prandoni, P.; Brighton, T.A. Aspirin for the prevention of recurrent venous thromboembolism: The INSPIRE collaboration. Circulation, 2014, 130(13), 1062-1071.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.008828] [PMID: 25156992]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.008828] [PMID: 25156992]
[12]
Moher, D.; Shamseer, L.; Clarke, M.; Ghersi, D.; Liberati, A.; Petticrew, M.; Shekelle, P.; Stewart, L.A. Preferred reporting items for sys-tematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev., 2015, 4(1), 1.
[http://dx.doi.org/10.1186/2046-4053-4-1] [PMID: 25554246]
[http://dx.doi.org/10.1186/2046-4053-4-1] [PMID: 25554246]
[13]
Chow, J.H.; Khanna, A.K.; Kethireddy, S.; Yamane, D.; Levine, A.; Jackson, A.M.; McCurdy, M.T.; Tabatabai, A.; Kumar, G.; Park, P.; Benjenk, I.; Menaker, J.; Ahmed, N.; Glidewell, E.; Presutto, E.; Cain, S.; Haridasa, N.; Field, W.; Fowler, J.G.; Trinh, D.; Johnson, K.N.; Kaur, A.; Lee, A.; Sebastian, K.; Ulrich, A.; Peña, S.; Carpenter, R.; Sudhakar, S.; Uppal, P.; Fedeles, B.T.; Sachs, A.; Dahbour, L.; Teeter, W.; Tanaka, K.; Galvagno, S.M.; Herr, D.L.; Scalea, T.M.; Mazzeffi, M.A. Aspirin Use Is Associated With Decreased Mechanical Ventila-tion, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019. Anesth. Analg., 2021, 132(4), 930-941.
[http://dx.doi.org/10.1213/ANE.0000000000005292] [PMID: 33093359]
[http://dx.doi.org/10.1213/ANE.0000000000005292] [PMID: 33093359]
[14]
Abdelwahab, H.W.; Shaltout, S.W.; Sayed Ahmed, H.A.; Fouad, A.M.; Merrell, E.; Riley, J.B.; Salama, R.; Abdelrahman, A.G.; Darling, E.; Fadel, G.; Elfar, M.S.A.; Sabry, K.; Shah, J.; Amin, H.; Nieman, G.F.; Mishriky, A.; Aiash, H. Acetylsalicylic acid compared with enoxapa-rin for the prevention of thrombosis and mechanical ventilation in COVID-19 patients: A retrospective cohort study. Clin. Drug Investig., 2021, 41(8), 723-732.
[http://dx.doi.org/10.1007/s40261-021-01061-2] [PMID: 34328635]
[http://dx.doi.org/10.1007/s40261-021-01061-2] [PMID: 34328635]
[15]
Yuan, S.; Chen, P.; Li, H.; Chen, C.; Wang, F.; Wang, D.W. Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 pa-tients with coronary artery disease. J. Cell. Mol. Med., 2021, 25(2), 1263-1273.
[http://dx.doi.org/10.1111/jcmm.16198] [PMID: 33336936]
[http://dx.doi.org/10.1111/jcmm.16198] [PMID: 33336936]
[16]
Sahai, A.; Bhandari, R.; Koupenova, M.; Freedman, J.; Godwin, M.; McIntyre, T. SARS-CoV-2 receptors are expressed on
human platelets and the effect of aspirin on clinical outcomes
in COVID-19 patients. Res Sq, 2020, rs-119031.
[http://dx.doi.org/10.2139/ssrn.3727292]
[http://dx.doi.org/10.2139/ssrn.3727292]
[17]
Reese, J.T.; Coleman, B.; Chan, L.; Blau, H.; Callahan, T.J.; Cappelletti, L. Cyclooxygenase inhibitor use is associated with increased COVID-19 severity. medRxiv, 2021.
[18]
Merzon, E.; Green, I.; Vinker, S.; Golan-Cohen, A.; Gorohovski, A.; Avramovich, E.; Frenkel-Morgenstern, M.; Magen, E. The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection. FEBS J., 2021, 288(17), 5179-5189.
[http://dx.doi.org/10.1111/febs.15784] [PMID: 33621437]
[http://dx.doi.org/10.1111/febs.15784] [PMID: 33621437]
[19]
Group, R.C. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet, 2021, 399(10320), 143-151.
[PMID: 34800427]
[PMID: 34800427]
[20]
Haji Aghajani, M.; Moradi, O.; Amini, H.; Azhdari Tehrani, H.; Pourheidar, E.; Rabiei, M.M.; Sistanizad, M. Decreased in-hospital mortali-ty associated with aspirin administration in hospitalized patients due to severe COVID-19. J. Med. Virol., 2021, 93(9), 5390-5395.
[http://dx.doi.org/10.1002/jmv.27053] [PMID: 33913549]
[http://dx.doi.org/10.1002/jmv.27053] [PMID: 33913549]
[21]
Liu, Q.; Huang, N.; Li, A.; Zhou, Y.; Liang, L.; Song, X.; Yang, Z.; Zhou, X. Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19. Medicine (Baltimore), 2021, 100(6), e24544.
[http://dx.doi.org/10.1097/MD.0000000000024544] [PMID: 33578548]
[http://dx.doi.org/10.1097/MD.0000000000024544] [PMID: 33578548]
[22]
Drew, D.A.; Guo, C-G.; Lee, K.A.; Nguyen, L.H.; Joshi, A.D.; Lo, C-H. Aspirin and NSAID use and the risk of COVID-19. medRxiv, 2021, 2021.04.28.21256261.
[http://dx.doi.org/10.1101/2021.04.28.21256261]
[http://dx.doi.org/10.1101/2021.04.28.21256261]
[23]
Meizlish, M.L.; Goshua, G.; Liu, Y.; Fine, R.; Amin, K.; Chang, E.; DeFilippo, N.; Keating, C.; Liu, Y.; Mankbadi, M.; McManus, D.; Wang, S.Y.; Price, C.; Bona, R.D.; Ochoa Chaar, C.I.; Chun, H.J.; Pine, A.B.; Rinder, H.M.; Siner, J.M.; Neuberg, D.S.; Owusu, K.A.; Lee, A.I. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis. Am. J. Hematol., 2021, 96(4), 471-479.
[http://dx.doi.org/10.1002/ajh.26102] [PMID: 33476420]
[http://dx.doi.org/10.1002/ajh.26102] [PMID: 33476420]
[24]
Osborne, T.F.; Veigulis, Z.P.; Arreola, D.M.; Mahajan, S.M.; Röösli, E.; Curtin, C.M. Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration. PLoS One, 2021, 16(2), e0246825.
[http://dx.doi.org/10.1371/journal.pone.0246825] [PMID: 33571280]
[http://dx.doi.org/10.1371/journal.pone.0246825] [PMID: 33571280]
[25]
Coulombe, F.; Jaworska, J.; Verway, M.; Tzelepis, F.; Massoud, A.; Gillard, J.; Wong, G.; Kobinger, G.; Xing, Z.; Couture, C.; Joubert, P.; Fritz, J.H.; Powell, W.S.; Divangahi, M. Targeted prostaglandin E2 inhibition enhances antiviral immunity through induction of type I in-terferon and apoptosis in macrophages. Immunity, 2014, 40(4), 554-568.
[http://dx.doi.org/10.1016/j.immuni.2014.02.013] [PMID: 24726877]
[http://dx.doi.org/10.1016/j.immuni.2014.02.013] [PMID: 24726877]
[26]
Berthelot, J.M.; Drouet, L.; Lioté, F. Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: Delayed over-activation of the STING pathway? Emerg. Microbes Infect., 2020, 9(1), 1514-1522.
[http://dx.doi.org/10.1080/22221751.2020.1785336] [PMID: 32574107]
[http://dx.doi.org/10.1080/22221751.2020.1785336] [PMID: 32574107]
[27]
Panka, B.A.; de Grooth, H.J.; Spoelstra-de Man, A.M.; Looney, M.R.; Tuinman, P.R. Prevention or treatment of ards with aspirin: A re-view of preclinical models and meta-analysis of clinical studies. Shock, 2017, 47(1), 13-21.
[http://dx.doi.org/10.1097/SHK.0000000000000745] [PMID: 27984533]
[http://dx.doi.org/10.1097/SHK.0000000000000745] [PMID: 27984533]
[28]
Bjornsson, T.D.; Schneider, D.E.; Berger, H., Jr Aspirin acetylates fibrinogen and enhances fibrinolysis. Fibrinolytic effect is independent of changes in plasminogen activator levels. J. Pharmacol. Exp. Ther., 1989, 250(1), 154-161.
[PMID: 2746495]
[PMID: 2746495]
[29]
Ornelas-Ricardo, D.; Jaloma-Cruz, A.R. Coronavirus Disease 2019: Hematological Anomalies and Antithrombotic Therapy. Tohoku J. Exp. Med., 2020, 251(4), 327-336.
[http://dx.doi.org/10.1620/tjem.251.327] [PMID: 32788506]
[http://dx.doi.org/10.1620/tjem.251.327] [PMID: 32788506]
[30]
Mahajan, P.; Dass, B.; Radhakrishnan, N.; McCullough, P.A. COVID-19-associated systemic thromboembolism: A case report and review of the literature. Cardiorenal Med., 2020, 10(6), 462-469.
[http://dx.doi.org/10.1159/000511800] [PMID: 33091905]
[http://dx.doi.org/10.1159/000511800] [PMID: 33091905]
[31]
Organization, WH. WHO recommends follow-up care, lowdose anticoagulants for COVID-19 patients. 2021.
[32]
Ikonomidis, I.; Andreotti, F.; Economou, E.; Stefanadis, C.; Toutouzas, P.; Nihoyannopoulos, P. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation, 1999, 100(8), 793-798.
[http://dx.doi.org/10.1161/01.CIR.100.8.793] [PMID: 10458713]
[http://dx.doi.org/10.1161/01.CIR.100.8.793] [PMID: 10458713]
[33]
Mehta, P.; McAuley, D.F.; Brown, M.; Sanchez, E.; Tattersall, R.S.; Manson, J.J. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet, 2020, 395(10229), 1033-1034.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[34]
Koupenova, M.; Kehrel, B.E.; Corkrey, H.A.; Freedman, J.E. Thrombosis and platelets: An update. Eur. Heart J., 2017, 38(11), 785-791.
[PMID: 28039338]
[PMID: 28039338]
[35]
Manne, B.K.; Denorme, F.; Middleton, E.A.; Portier, I.; Rowley, J.W.; Stubben, C.; Petrey, A.C.; Tolley, N.D.; Guo, L.; Cody, M.; Wey-rich, A.S.; Yost, C.C.; Rondina, M.T.; Campbell, R.A. Platelet gene expression and function in patients with COVID-19. Blood, 2020, 136(11), 1317-1329.
[http://dx.doi.org/10.1182/blood.2020007214] [PMID: 32573711]
[http://dx.doi.org/10.1182/blood.2020007214] [PMID: 32573711]
[36]
Diaz, T.; Trachtenberg, B.H.; Abraham, S.J.K. KosagiSharaf, R.; Durant-Archibold, A.A. Aspirin bioactivity for prevention of cardiovas-cular injury in COVID-19. Front. Cardiovasc. Med., 2020, 7, 562708.
[http://dx.doi.org/10.3389/fcvm.2020.562708] [PMID: 33330639]
[http://dx.doi.org/10.3389/fcvm.2020.562708] [PMID: 33330639]
[37]
Li, B.; Yang, J.; Zhao, F.; Zhi, L.; Wang, X.; Liu, L.; Bi, Z.; Zhao, Y. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin. Res. Cardiol., 2020, 109(5), 531-538.
[http://dx.doi.org/10.1007/s00392-020-01626-9] [PMID: 32161990]
[http://dx.doi.org/10.1007/s00392-020-01626-9] [PMID: 32161990]
[38]
Matsushita, K.; Ding, N.; Kou, M.; Hu, X.; Chen, M.; Gao, Y.; Honda, Y.; Zhao, D.; Dowdy, D.; Mok, Y.; Ishigami, J.; Appel, L.J. The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis. Glob. Heart, 2020, 15(1), 64.
[http://dx.doi.org/10.5334/gh.814] [PMID: 33150129]
[http://dx.doi.org/10.5334/gh.814] [PMID: 33150129]
[39]
Teuwen, L.A.; Geldhof, V.; Pasut, A.; Carmeliet, P. COVID-19: The vasculature unleashed. Nat. Rev. Immunol., 2020, 20(7), 389-391.
[http://dx.doi.org/10.1038/s41577-020-0343-0] [PMID: 32439870]
[http://dx.doi.org/10.1038/s41577-020-0343-0] [PMID: 32439870]
[40]
Salah, H.M.; Mehta, J.L. Meta-analysis of the effect of aspirin on mortality in COVID-19. Am. J. Cardiol., 2021, 142, 158-159.
[http://dx.doi.org/10.1016/j.amjcard.2020.12.073] [PMID: 33417877]
[http://dx.doi.org/10.1016/j.amjcard.2020.12.073] [PMID: 33417877]
[41]
Srivastava, R.; Kumar, A. Use of aspirin in reduction of mortality of COVID-19 patients: A meta-analysis. Int. J. Clin. Pract., 2021, 75(11), e14515.
[http://dx.doi.org/10.1111/ijcp.14515] [PMID: 34118111]
[http://dx.doi.org/10.1111/ijcp.14515] [PMID: 34118111]
[42]
Kow, C.S.; Hasan, S.S. Use of antiplatelet drugs and the risk of mortality in patients with COVID-19: A meta-analysis. J. Thromb. Thrombolysis, 2021, 52(1), 124-129.
[http://dx.doi.org/10.1007/s11239-021-02436-0] [PMID: 33813716]
[http://dx.doi.org/10.1007/s11239-021-02436-0] [PMID: 33813716]
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