Iberoamerican Journal of Medicine
Iberoamerican Journal of Medicine

The Novel Aspirin as Breakthrough Drug for COVID-19: A Narrative Review

Bamidele Johnson Alegbeleye, Oke-Oghene Philomena Akpoveso, Adewale James Alegbeleye, Rana Kadhim Mohammed, Eduardo Esteban-Zubero

Downloads: 31
Views: 5860


Introduction: Aspirin has justifiably been called the first miracle drug. In this article, we highlight the history of Aspirin, a novel mechanism of action, and its use in cardiovascular and other diseases. Also included is a brief statement of emerging new applications.
Objective: We highlight principal mechanisms by which Aspirin inhibits acute inflammation and alters platelet-biology; therefore, hypothesized that Aspirin might prove highly beneficial as a novel therapeutic drug for combating severe acute inflammation and thrombosis associated with the cytokine storm in COVID -19 patients. The communiqué also suggests possible strategies for maximizing the gain of Aspirin as a wonder-drug of the future.
Discussion: Interestingly, some fascinating studies demonstrated Aspirin's superior benefits with dangerous side effects. Aspirin inhibits COX-1 (cyclooxygenase-1). Its impact on COX-2 is more delicate because it “turns off” COX-2's production of prostaglandins but “switches on” the enzymatic ability to produce novel protective lipid mediators. The established mechanism of action of Aspirin is the inhibition of prostaglandin synthesis. However, further evidence showed that aspirin-elicited nitric oxide exerts anti-inflammatory effects in the microcirculation by inhibiting leukocyte– endothelium interactions. Interestingly, aspirin-triggered lipoxin formation may provide a novel mechanism underlying Aspirin's clinical benefits. Interestingly, Aspirin reduces the risk of a cardiovascular event by about 30 percent. Also, Aspirin has been associated with a reduced risk of colorectal cancer, and possibly a few other digestive tract cancers.
Conclusion: The current emerging interest is to conduct further study to provide evidence for Aspirin as the novel therapeutic drug for combating severe acute inflammation and thrombosis associated with the cytokine storm in COVID-19 patients. Besides, the most wanted is The RECOVERY II (Randomized Evaluation of COVID-19 Therapy II) trial to be established as a randomized clinical trial to test the effectiveness of low-dose Aspirin as an anti-inflammatory and antithrombotic treatment in COVID-19 patients.


Aspirin; COVID-19; Systemic inflammatory response; Cytokine storm; Nonsteroidal antiinflammatory drugs; SARS-CoV-2; Steroids


1. Alegbeleye BJ, Coker AO, Ohene JE, Oke OA, Jantchou P, Mohammed RK. The Global Impact of COVID-19 Pandemic on General Surgical Services. In J Healthc Sci. 2020;8(1):104-19.
2. Jantchou P, Alegbeleye BJ, Nguyen V. Physician Roles and Responsibilities in the Context of a Pandemic in Resource-Limited Areas: Impact of Social Media. Iberoam J Med. 2020;2(3):201-14. doi: 10.5281/zenodo.3813830.
3. Patel KS, Rathi JC, Raghuvanshi K, Dhiman N. Coronavirus (SARS-CoV-2): Preventions, keys to diagnosis and treatment of SARS-CoV-2. Iberoam J Med. 2020;2(2):87-99. doi: 10.5281/zenodo.3715266.
4. World Health Organization. Available from:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technicalguidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-thatcauses-it (accessed June 2020)
5. Koh T, Bee T, Plant AJ, Lee EH. The New Global Threat: Severe Acute Respiratory Syndrome And Its Impacts. World Scientific Publishing Co; 2003.
6. WHO. World Health Organization Updates on Coronavirus-2019. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance (accessed June 2020)
7. Kavanagh MM. Authoritarianism, outbreaks, and information politics. Lancet Public Health. 2020;5(3):e135-e136. doi: 10.1016/S2468-2667(20)30030-X.
8. WHO. WHO Director-General‘s remarks at the media briefing on COVID-
2019 outbreak on 19 June 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-openingremarks-at-the-media-briefing-on-covid-19---19-june-2020 (accessed June 2020)
9. Özdemir Ö. Coronavirus Disease 2019 (COVID-19): Diagnosis and Management. Erciyes Med J. 2020; 42(3): 242-7. doi: 10.14744/etd.2020.99836.
10. Conti P, Gallenga CE, Tetè G, Caraffa A, Ronconi G, Younes A, et al. How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. J Biol Regul Homeost Agents. 2020;34(2):10.23812/Editorial-Conti-2. doi: 10.23812/Editorial-Conti-2.
11. Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health. 2020;25(3):278-280. doi: 10.1111/tmi.13383.
12. Velavan TP, Meyer CG. Mild versus severe COVID-19: Laboratory markers. Int J Infect Dis. 2020;95:304-307. doi: 10.1016/j.ijid.2020.04.061.
13. Reuters. China approves use of Roche drug in battle against coronavirus complications. Available from: https://www.reuters.com/article/us-healthcoronavirus-china-roche-hldg/china-approves-use-of-roche-arthritis-drug-forcoronavirus-patients-idUSKBN20R0LF (accessed June 2020)
14. University of Oxford. Low-cost dexamethasone reduces death by up to one third in hospitalized patients with severe respiratory complications of COVID-19. Available from: https://www.ox.ac.uk/news/2020-06-16-low-cost-dexamethasone-reduces-death-one-third-hospitalised-patients-severe (accessed June 2020)
15. Oluwaseyi IG. The Perceived Accompanying Dangers of Dexamethasone (A Corticosteroid) Use in Covid-19 Management. doi: 10.6084/m9.figshare.12509807.
16. Dvorin EL, Ebell MH. Short-Term Systemic Corticosteroids: Appropriate Use in Primary Care. Am Fam Physician. 2020;101(2):89-94.
17. Ornelas A, Zacharias-Millward N, Menter DG, Davis JS, Lichtenberger L, Hawke D et al. Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Rev. 2017;36(2):289-303. doi: 10.1007/s10555-017-9675-z.
18. Elwood P, Stillings M. New uses for old drugs: Aspirin — the first miracle drug. The Pharmaceutical Journal. Available from: https://www.pharmaceutical-journal.com/learning/learning-article/new-usesfor- old-drugs-aspirin-the-first-miracle-drug/20004121.article?firstPass=false
19. Pierpoint WS. The natural history of salicylic acid, plant product and mammalian medicine. Interdisciplinary Sci Rev. 1997;22(1):45-52. doi: 10.1179/isr.1997.22.1.45.
20. Stone E. An account of the success of the bark of the willow in the cure of agues. Philos Trans. 1763; 53:195-200. doi: 10.1098/rstl.1763.0033.
21. Wohlgemuth J. Ueber Aspirin (Acetylsalicysäure). Therap Monatshefte. 1899;3:276-8.
22. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G. Aspirin, salicylates, and cancer. Lancet. 2009;373(9671):1301-9. doi: 10.1016/S0140-6736(09)60243-9.
23. Morgan G. Beneficial effects of NSAIDs in the gastrointestinal tract. Eur J Gastroenterol Hepatol. 1999;11(4):393-400. doi: 10.1097/00042737-199904000-00006.
24. Matsui T, Abe K, Honda T, Yasukawa K, Takanashi JI, Hamada H Aspirin Dose and Treatment Outcomes in Kawasaki Disease: A Historical Control Study in Japan. Front Pediatr. 2020;8:249. doi: 10.3389/fped.2020.00249.
25. Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers toes in children]. Arerugi. 1967;16(3):178-222.
26. Gordon JB, Kahn AM, Burns JC. When children with Kawasaki disease grow up: Myocardial and vascular complications in adulthood. J Am Coll Cardiol. 2009;54(21):1911-20. doi: 10.1016/j.jacc.2009.04.102.
27. Chiang N, Serhan CN. Aspirin triggers formation of anti-inflammatory mediators: New mechanism for an old drug. Discov Med. 2004;4(24):470-5.
28. Needleman P, Isakson PC. The discovery and function of COX-2. J Rheumatol Suppl. 1997;49:6-8.
29. Serhan CN, Chiang N. Novel endogenous small molecules as the checkpoint controllers in inflammation and resolution: entrée for resoleomics. Rheum Dis Clin North Am. 2004;30(1):69-95. doi: 10.1016/S0889-857X(03)00117-0.
30. Clària J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A. 1995;92(21):9475-9. doi: 10.1073/pnas.92.21.9475.
31. Chiang N, Takano T, Clish CB, Petasis NA, Tai HH, Serhan CN. Aspirintriggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA. J Pharmacol Exp Ther. 1998;287(2):779-90.
32. Chiang N, Bermudez EA, Ridker PM, Hurwitz S, Serhan CN. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci U S A. 2004;101(42):15178-15183. doi: 10.1073/pnas.0405445101.
33. Marcus AJ, Broekman MJ, Pinsky DJ. COX inhibitors and thromboregulation. N Engl J Med. 2002;347(13):1025-6. doi: 10.1056/NEJMcibr021805.
34. Fiorucci S, Distrutti E, de Lima OM, Romano M, Mencarelli A, Barbanti M, et al. Relative contribution of acetylated cyclo-oxygenase (COX)-2 and 5- lipooxygenase (LOX) in regulating gastric mucosal integrity and adaptation to aspirin. FASEB J. 2003;17(9):1171-1173. doi: 10.1096/fj.02-0777fje.
35. Paul-Clark MJ, Van Cao T, Moradi-Bidhendi N, Cooper D, Gilroy DW. 15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation. J Exp Med. 2004;200(1):69-78. doi: 10.1084/jem.20040566.
36. Faiq MA, Kumar A, Singh HN, Pareek V, Qadri R, Raza K, et al. COVID-19: A review on molecular basis, pathogenic mechanisms, therapeutic aspects and future projections. doi: 10.20944/preprints202004.0091.v1.
37. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment Coronavirus (COVID-19). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
38. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol. 2020;15(5):700-4. doi: 10.1016/j.jtho.2020.02.010.
39. Gralinski LE, Baric RS. Molecular pathology of emerging coronavirus infections. J Pathol. 2015;235(2):185-95. doi: 10.1002/path.4454.
40. Qian Z, Travanty EA, Oko L, Edeen K, Berglund A, Wang J, et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013;48(6):742-8. doi: 10.1165/rcmb.2012-0339OC.
41. Zhang H, Zhou P, Wei Y, Yue H, Wang Y, Hu M, et al. Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19. Ann Intern Med. 2020;172(9):629-32. doi: 10.7326/M20-0533.
42. Zhang J, Tian S, Lou J, Chen Y. Familial cluster of COVID-19 infection from an asymptomatic. Crit Care. 2020;24(1):119. doi: 10.1186/s13054-020-2817-7.
43. Zhang S, Diao M, Yu W, Pei L, Lin Z, Chen D. Estimation of the reproductive number of novel coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis. Int J Infect Dis. 2020;93:201-4. doi: 10.1016/j.ijid.2020.02.033.
44. Zhang T, Wu Q, Zhang Z. Probable Pangolin Origin of SARS-CoV2 Associated with the COVID-19 Outbreak. Curr Biol. 2020; 30(7):1346-51.e2. doi: 10.1016/j.cub.2020.03.022.
45. Zhang XA, Fan H, Qi RZ, Zheng W, Zheng K, Gong JH, et al. Importing coronavirus disease 2019 (COVID-19) into China after international air travel. Travel Med Infect Dis. 2020;35:101620. doi: 10.1016/j.tmaid.2020.101620.
46. Mossel EC, Wang J, Jeffers S, Edeen KE, Wang S, Cosgrove GP, et al. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology. 2008;372(1):127-35. doi: 10.1016/j.virol.2007.09.045.
47. Ward HE, Nicholas TE. Alveolar type I and type II cells. Aust N Z J Med. 1984;14(5 Suppl 3):731-4.
48. Sugahara, K. [Regulation of alveolar type II cell proliferation and surfactant gene expression]. Nihon Kyobu Shikkan Gakkai Zasshi. 1994;32 Suppl:73-8.
49. Helewski K, Konecki J. [Alveolar cells type II, their role in the biosynthesis of pulmonary surfactant and other functions]. Pol Tyg Lek. 1989;44(2-3):58-62.
50. Ortega JT, Serrano ML, Pujol FH, Rangel HR. Role of changes in SARSCoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis. EXCLI J. 2020;19:410-417. doi: 10.17179/excli2020-1167.
51. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809-15. doi: 10.1016/S0140-6736(20)30360-3.
52. Chen D, Xu W, Lei Z, Huang Z, Liu J, Gao Z, Peng L. Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report. Int J Infect Dis. 2020;93:297-9. doi: 10.1016/j.ijid.2020.03.003.
53. Chen X, Yu B. First two months of the 2019 Coronavirus Disease (COVID-19) epidemic in China: real-time surveillance and evaluation with a second derivative model. Glob Health Res Policy. 2020;5:7. doi: 10.1186/s41256-020-00137-4.
54. Roca-Ho H, Riera M, Palau V, Pascual J, Soler MJ. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse. Int J Mol Sci. 2017;18(3):563. doi: 10.3390/ijms18030563.
55. Varagic J, Ahmad S, Nagata S, Ferrario CM. ACE2: angiotensin II/angiotensin-(1-7) balance in cardiac and renal injury. Curr Hypertens Rep. 2014;16(3):420. doi: 10.1007/s11906-014-0420-5.
56. Tikellis C, Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease. Int J Pept. 2012;2012:256294. doi: 10.1155/2012/256294.
57. Ocaranza MP, Jalil JE. Protective Role of the ACE2/Ang-(1-9) Axis in Cardiovascular Remodeling. Int J Hypertens. 2012;2012:594361. doi: 10.1155/2012/594361.
58. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7. doi: 10.1002/path.1570.
59. Faiq MA, Kumar A, Singh HN, Pareek V, Kumar P. Commentary: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome. Front Microbiol. 2018;9:190. doi: 10.3389/fmicb.2018.00190.
60. Kumar A, Singh HN, Pareek V, Raza K, Dantham S, Kumar P, et al. A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome. Front Hum Neurosci. 2016;10:403. doi: 10.3389/fnhum.2016.00403.
61. Ibrahim IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spikehost cell receptor GRP78 binding site prediction. J Infect. 2020;80(5):554-62. doi: 10.1016/j.jinf.2020.02.026.
62. Ahmed SF, Quadeer AA, McKay MR. Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies. Viruses. 2020;12(3):254. doi: 10.3390/v12030254.
63. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020;92(6):595-601. doi: 10.1002/jmv.25726.
64. Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect. 2020;9(1):382-5. doi: 10.1080/22221751.2020.1729069.
65. Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020;9(1):601-4. doi: 10.1080/22221751.2020.1739565.
66. Kim JM, Chung YS, Jo HJ, Lee NJ, Kim MS, Woo SH, et al. Identification of Coronavirus Isolated from a Patient in Korea with COVID-19. Osong Public Health Res Perspect. 2020;11(1):3-7. doi: 10.24171/j.phrp.2020.11.1.02.
67. McIntyre W, Netzband R, Bonenfant G, Biegel JM, Miller C, Fuchs G, et al. Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection. Nucleic Acids Res. 2018;46(11):5776-91. doi: 10.1093/nar/gky029.
68. Poltronieri P, Sun B, Mallardo M. RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load. Curr Genomics. 2015;16(5):327-35. doi: 10.2174/1389202916666150707160613.
69. Hyodo K, Okuno T. Pathogenesis mediated by proviral host factors involved in translation and replication of plant positive-strand RNA viruses. Curr Opin Virol. 2016;17:11-8. doi: 10.1016/j.coviro.2015.11.004.
70. Richards AL, Jackson WT. How positive-strand RNA viruses benefit from autophagosome maturation. J Virol. 2013;87(18):9966-72. doi: 10.1128/JVI.00460-13.
71. Wang RY, Li K. Host factors in the replication of positive-strand RNA viruses. Chang Gung Med J. 2012;35(2):111-24. doi: 10.4103/2319-4170.106160.
72. Ahlquist P, Noueiry AO, Lee WM, Kushner DB, Dye BT. Host factors in positive-strand RNA virus genome replication. J Virol. 2003;77(15):8181-6. doi: 10.1128/jvi.77.15.8181-8186.2003.
73. Martinez MA. Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Antimicrob Agents Chemother. 2020;64(5):e00399-20. doi: 10.1128/AAC.00399-20.
74. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir- Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-99. doi: 10.1056/NEJMoa2001282.
75. Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6):556-63. doi: 10.1002/jmv.25729.
76. Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR. J Korean Med Sci. 2020;35(6):e79. doi: 10.3346/jkms.2020.35.e79.
77. Zinzula L, Tramontano E. Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I-like receptors: hide, mask, hit. Antiviral Res. 2013;100(3):615-35. doi: 10.1016/j.antiviral.2013.10.002.
78. Freeman AM, Leigh, Jr TR. Viral Pneumonia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
79. Naeem A, Rai SN, Pierre L. Histology, Alveolar Macrophages. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
80. Herbert C, Scott MM, Scruton KH, Keogh RP, Yuan KC, Hsu K, et al. Alveolar macrophages stimulate enhanced cytokine production by pulmonary CD4+ T-lymphocytes in an exacerbation of murine chronic asthma. Am J Pathol. 2010;177(4):1657-64. doi: 10.2353/ajpath.2010.100019.
81. Losa Garcia JE, Rodriguez FM, Martin de Cabo MR, Garcia Salgado MJ, Losada JP, Villaron LG, et al. Evaluation of inflammatory cytokine secretion by human alveolar macrophages. Mediators Inflamm. 1999;8(1):43-51. doi: 10.1080/09629359990711.
82. Driscoll KE, Maurer JK, Higgins J, Poynter J. Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis. J Toxicol Environ Health. 1995;46(2):155-69. doi: 10.1080/15287399509532026.
83. Ward HE, Nicholas TE. Alveolar type I and type II cells. Aust N Z J Med. 1984;14(5 Suppl 3):731-4.
84. Powers KA, Dhamoon AS. Physiology, Pulmonary, Ventilation and Perfusion. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019.
85. Wan KH, Huang SS, Young AL, Lam DSC. Precautionary measures needed for ophthalmologists during pandemic of the coronavirus disease 2019 (COVID-19). Acta Ophthalmol. 2020;98(3):221-2. doi: 10.1111/aos.14438.
86. Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol. 2020;92(7):797-806. doi: 10.1002/jmv.25783.
87. He F, Deng Y, Li W. Coronavirus disease 2019: What we know? J Med Virol. 2020;92(7):719-25. doi: 10.1002/jmv.25766.
88. Hoffman R, Benz Jr. EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J. Haematology: Basic Principles and Practice. 6th ed. Elsevier Saunders; 2013.
89. Kumar P, Clark M. Clinical Medicine: A Textbook for Medical Students and Doctors. 4th ed. Philadelphia: W.B. Saunders; 1998.
90. Kumar V, Abbas AK, Fausto N, Mitchell RN. Robbins Basic Pathology. 8th ed. Saunders Elsevier; 2007.
91. Bujaa LM, Wolf DA, Zhaoa B, Akkanti B, McDonalda M, Lelenwaa L, et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol. 2020;48:107233. doi: 10.1016/j.carpath.2020.107233.
92. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020;382(20):e60. doi: 10.1056/NEJMc2009787.
93. Andrews RK, Arthur JF, Gardiner EE. Neutrophil extracellular traps (NETs) and the role of platelets in infection. Thromb Haemost. 2014;112(4):659-65. doi: 10.1160/TH14-05-0455.
94. Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652. doi: 10.1084/jem.20200652.
95. 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. J Thromb Haemost. 2020;18(5):1094-9. doi: 10.1111/jth.14817.
96. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14. doi: 10.1016/j.thromres.2020.04.024.
97. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-7. doi: 10.1016/j.thromres.2020.04.013.
98. Belen-Apak FB, Sarıalioğlu F. Pulmonary intravascular coagulation in COVID-19: possible pathogenesis and recommendations on anticoagulant/thrombolytic therapy. J Thromb Thrombolysis. 2020;50(2):278-80. doi: 10.1007/s11239-020-02129-0.
99. Azboy I, Barrack R, Thomas AM, Haddad FS, Parvizi J. Aspirin and the prevention of venous thromboembolism following total joint arthroplasty: commonly asked questions. Bone Joint J. 2017;99-B(11):1420-30. doi: 10.1302/0301-620X.99B11.BJJ-2017-0337.R2.
100. Gupta E, Siddiqi FS, Kunjal R, Faisal M, Al-Saffar F, Bajwa AA, et al. Association between aspirin use and deep venous thrombosis in mechanically ventilated ICU patients. J Thromb Thrombolysis. 2017;44(3):330-4. doi: 10.1007/s11239-017-1525-x.
101. Undas A, Brummel-Ziedins K, Mann KG. Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid. J Thromb Haemost. 2014;12(11):1776-87. doi: 10.1111/jth.12728.
102. Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971;231(25):235-7. doi: 10.1038/newbio231235a0.
103. Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975;56(3):624-32. doi: 10.1172/JCI108132.
104. Ebbeling L, Robertson C, McNicol A, Gerrard JM. Rapid ultrastructural changes in the dense tubular system following platelet activation. Blood. 1992;80(3):718-23.
105. Gerrard JM, White JG, Rao GH, Townsend D. Localization of platelet prostaglandin production in the platelet dense tubular system. Am J Pathol. 1976;83(2):283-98.
106. Xu Y, Phipps S, Turner MJ, Simmons DL. The N-terminus of COX-1 and its effect on cyclooxygenase-1 catalytic activity. J Genet Genomics. 2010;37(2):117-23. doi: 10.1016/S1673-8527(09)60030-8.
107. Loll PJ, Picot D, Garavito RM. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat Struct Biol. 1995;2(8):637-43. doi: 10.1038/nsb0895-637.
108. Hamberg M, Samuelsson B. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A. 1973;70(3):899-903. doi: 10.1073/pnas.70.3.899.
109. Hamberg M, Svensson J, Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975;72(8):2994-8. doi: 10.1073/pnas.72.8.2994.
110. Knapp HR, Oelz O, Sweetman BJ, Oates JA. Synthesis and metabolism of prostaglandins E2, F2alpha and D2 by the rat gastrointestinal tract. Stimulation by a hypertonic environment in vitro. Prostaglandins. 1978;15(5):751-7. doi: 10.1016/0090-6980(78)90141-7.
111. Peskar BM. On the synthesis of prostaglandins by human gastric mucosa and its modification by drugs. Biochim Biophys Acta. 1977;487(2):307-14. doi: 10.1016/0005-2760(77)90007-8.
112. Darling RL, Romero JJ, Dial EJ, Akunda JK, Langenbach R, Lichtenberger LM. The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice. Gastroenterology. 2004;127(1):94-104. doi: 10.1053/j.gastro.2004.04.003.
113. Saniabadi AR, Lowe GD, Belch JJ, Barbenel JC, Forbes CD. Effect of prostacyclin (epoprostenol) on the aggregation of human platelets in whole blood in vitro. Haemostasis. 1984;14(6):487-94. doi: 10.1159/000215110.
114. Rocca B, Secchiero P, Ciabattoni G, Ranelleti FO, Catani L, Guidotti L, et al. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci U S A. 2002;99(11):7634-9. doi: 10.1073/pnas.112202999.
115. Zetterberg E, Lundberg LG, Palmblad J. Expression of cox-2, tie-2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera. Br J Haematol. 2003;121(3):497-9. doi: 10.1046/j.1365-2141.2003.04289.x.
116. Hu Q, Cho MS, Thiagarajan P, Aung FM, Sood AK, Afshar-Kharghan V. A small amount of cyclooxygenase 2 (COX2) is constitutively expressed in platelets. Platelets. 2017;28(1):99-102. doi: 10.1080/09537104.2016.1203406.117. Mulugeta S, Suzuki T, Hernandez NT, Griesser M, Boeglin WE, Schneider
C. Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2. J Lipid Res. 2010;51(3):575-85. doi: 10.1194/jlr.M001719.
118. Rowlinson SW, Crews BC, Goodwin DC, Schneider C, Gierse JK, Marnett LJ. Spatial requirements for 15-(R)-hydroxy-5Z,8Z,11Z, 13Eeicosatetraenoic acid synthesis within the cyclooxygenase active site of murine COX-2. Why acetylated COX-1 does not synthesize 15-(R)-hete. J Biol Chem. 2000;275(9):6586-91. doi: 10.1074/jbc.275.9.6586.
119. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F. Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999;26(6):1366-73.
120. Sharma NP, Dong L, Yuan C, Noon KR, Smith WL. Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. Mol Pharmacol. 2010;77(6):979-86. doi: 10.1124/mol.109.063115.
121. Dovizio M, Bruno A, Tacconelli S, Patrignani P. Mode of action of aspirin as a chemopreventive agent. Recent Results Cancer Res. 2013;191:39-65. doi: 10.1007/978-3-642-30331-9_3.
122. Block RC, Kakinamia L, Jonovichc M, Antonettic I, Lawrenced P, Meednue N, et al. The combination of EPA+DHA and low-dose aspirin ingestion reduces platelet function acutely whereas each alone may not in healthy humans. Prostaglandins Leukot Essent Fatty Acids. 2012;87(4-5):143-51. doi: 10.1016/j.plefa.2012.08.007.
123. Bosetti C, Santucci C, Gallus S, Martinetti M, La Vecchia C. Aspirin and the risk of colorectal and other digestive tract cancers: an updated metaanalysis through 2019. Ann Oncol. 2020;31(5):558-68. doi: 10.1016/j.annonc.2020.02.012.
124. Ishikawa H, Wakabayashi K, Suzuki S, Mutoh M, Hirata K, Nakamura T, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Cancer Med. 2013;2(1):50-6. doi: 10.1002/cam4.46.
125. Bosetti C, Rosato V, Gallus S, Cuzick J, La Vecchia C. Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol. 2012;23(6):1403-15. doi: 10.1093/annonc/mds113.
126. Bardia A, Ebbert JO, Vierkant RA, Limburg PJ, Anderson K, Wang AH, et al. Association of aspirin and nonaspirin nonsteroidal antiinflammatory drugs with cancer incidence and mortality. J Natl Cancer Inst. 2007;99(11):881-9. doi: 10.1093/jnci/djk200.
127. Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167(6):562-72. doi: 10.1001/archinte.167.6.562.
128. Jacobs EJ, Newton CC, Gapstur SM, Thun MJ. Daily aspirin use and cancer mortality in a large US cohort. J Natl Cancer Inst. 2012;104(16):1208-17. doi: 10.1093/jnci/djs318.
129. Ratnasinghe LD, Graubard BI, Kahle L, Tangrea JA, Taylor PR, Hawk E. Aspirin use and mortality from cancer in a prospective cohort study. Anticancer Res. 2004;24(5B):3177-84.
130. Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003;348(10):883-90. doi: 10.1056/NEJMoa021633.
131. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348(10):891-9. doi: 10.1056/NEJMoa021735.
132. Benamouzig R, Deyra J, Martin A, Girard B, Jullian E, Piednoir B, et al. Daily soluble aspirin and prevention of colorectal adenoma recurrence: oneyear results of the APACC trial. Gastroenterology. 2003;125(2):328-36. doi: 10.1016/s0016-5085(03)00887-4.
133. Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081-7. doi: 10.1016/S0140-6736(11)61049-0.
134. Drew DA, Chin SM, Gilpin KK, Parziale M, Pond E, Schuck MM et al. ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED): a study protocol for a randomized controlled trial. Trials. 2017;18(1):50. doi: 10.1186/s13063-016-1744-z.
135. Alegbeleye BJ, Mohammed RK. Challenges of healthcare delivery in the context of COVID-19 pandemic in Sub-Saharan Africa. Iberoam J Med. 2020;2(2):100-9. doi: 10.5281/zenodo.3755414.

Submitted date:

Reviewed date:

Accepted date:

Publication date:

5f27e24b0e882515560e4939 iberoamericanjm Articles
Links & Downloads

Iberoam J Med

Share this page
Page Sections