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Aspirin and COVID-19. Dec 15th, 2020

  • December 15, 2020
Covid 19

Professor Mazzeffi
Maryland, USA

During the 2020 pandemic our understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly evolved. We now know that coronavirus disease 2019 (COVID-19), is a multi-system disorder characterized by endothelial cell dysfunction and hypercoagulability.[1-3] Early during the pandemic, one of my cardiac surgical colleagues noted that a patient with severe COVID-19 had extreme hypercoagulability during an ECMO cannulation. There were also multiple reports of increased myocardial infarction and ischemic stroke in COVID-19 patients published from New York City. This information led my colleague, Dr. Jonathan Chow, and I to begin thinking about aspirin as a potential treatment for COVID-19. Two landmark autopsy studies definitively showed that SARS-CoV-2 infects endothelial cells, which furthered our interest in aspirin as a therapeutic agent.[4, 5]

Aspirin is perhaps the most widely used pharmaceutical and it has a well-established risk profile. It is recommended for primary prevention of cardiovascular events in patients 40 to 70 years of age who are not at increased bleeding risk.[6] Aspirin irreversibly inhibits cyclooxygenase reducing platelet aggregation. This property may also help aspirin to reduce microthrombi in COVID-19 patients. In addition, salicylic acid has anti-viral properties and attenuates the pro-inflammatory effects of the transcription factor NF-kappa B, which has been implicated as having a critical role in the cytokine storm that occurs with COVID-19.[7-10] Finally, aspirin acetylates fibrinogen, which enhances its breakdown.[11] This may be important in COVID-19 because fibrinogen levels are supra-normal.

In a multi-center observational cohort study of 412 COVID-19 patients, my colleagues and I found that aspirin use was associated with a significant reduction in the risk of intensive care unit admission, mechanical ventilation, and in-hospital death.[12] Notably, aspirin did not increase bleeding or other complications. Although, this study was not a randomized controlled trial, its findings were notable as aspirin is the first inexpensive, widely available drug found to reduce mortality in COVID-19 patients. According to clinicaltrials.gov, there are multiple ongoing randomized controlled trials of aspirin in COVID-19 patients including: PEAC (Protective effects of aspirin on COVID-19 patients), LEAD-COVID (Low risk, early aspirin and Vitamin D to reduce Covid-10 hospitalizations), and RECOVERY. These trials should help to definitively determine whether aspirin reduces illness severity or death in COVID-19.

References

[1] Mazzeffi MA, Chow JH, Tanaka K. COVID-19 Associated Hypercoagulability: Manifestations, Mechanisms, and Management. Shock. 2020.
[2] Desborough MJR, Doyle AJ, Griffiths A, Retter A, Breen KA, Hunt BJ. Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom. Thromb Res. 2020;193:1-4.
[3] Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, Kucher N, Studt JD, Sacco C, Alexia B, Sandri MT, Barco S, Humanitas C-TF. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14.
[4] Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020.
[5] Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020.
[6] Arnett DK, Khera A, Blumenthal RS. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Part 1, Lifestyle and Behavioral Factors. JAMA Cardiol. 2019;4:1043-4.
[7] Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients. Inflammopharmacology. 2020.
[8] Zhang X, Wu K, Wang D, Yue X, Song D, Zhu Y, Wu J. Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. Virology. 2007;365:324-35.
[9] Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 1994;265:956-9.
[10] Glatthaar-Saalmuller B, Mair KH, Saalmuller A. Antiviral activity of aspirin against RNA viruses of the respiratory tract-an in vitro study. Influenza Other Respir Viruses. 2017;11:85-92.
[11] Bjornsson TD, Schneider DE, Berger H, Jr. Aspirin acetylates fibrinogen and enhances fibrinolysis. Fibrinolytic effect is independent of changes in plasminogen activator levels. J Pharmacol Exp Ther. 1989;250:154-61.
[12] Chow JH, Khanna AK, Kethireddy S, Yamane D, Levine A, Jackson AM, McCurdy MT, Tabatabai A, Kumar G, Park P, Benjenk I, Menaker J, Ahmed N, Glidewell E, Presutto E, Cain S, Haridasa N, Field W, Fowler JG, Trinh D, Johnson KN, Kaur A, Lee A, Sebastian K, Ulrich A, Pena S, Carpenter R, Sudhakar S, Uppal P, Fedeles BT, Sachs A, Dahbour L, Teeter W, Tanaka K, Galvagno SM, Herr DL, Scalea TM, Mazzeffi MA. Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19. Anesth Analg. 2020.

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Daniel José Piñeiro

ASSOCIATE
Name
Daniel José Piñeiro
Academic Affiliations:
Full Professor of Medicine, Universidad de Buenos Aires, Argentina Trustee, Board of Trustees, American College of Cardiology
Professional Setting:
My academic experience includes more than 40 years as a practicing medical doctor, teacher, and researcher. I have fulfilled these appointments in settings of vital social engagement and impact, most notably at the Hospital de Clínicas “José de San Martín” of the Universidad de Buenos Aires, a public hospital with high academic recognition. Additionally, I currently hold the position of Full Professor of Medicine at that same University.
Academic Activities:
  • International Meetings Participations: 180
  • Books-Editor: 1
  • Books Chapters: 39
  • Refereed Full Articles: 118 (listed in Pubmed: 29)
  • Refereed Abstracts: 221
  • Editorial Boards: 10
Profesional Associations:
  • 2005 President, Sociedad Argentina de Cardiología.
  • 2011-2013 President, Inter-American Society of Cardiology.
  • 2011-2013 Member (ex-officio), Board of Directors, World Heart Federation
  • 2017-2018 Member (at large), Board of Directors, World Heart Federation
  • 2018-2021 Trustee, Board of Trustees, American College of Cardiology
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Chia

John Chia

Name
John Chia MBBS (Spore), MRCP (UK), FAMS (Spore)
Academic Affiliations:

Adjunct Associate Professor DUKE-NUS Graduate Medical School,
Consultant Oncologist Curie Oncology Singapore,
Visiting Consultant National Cancer Centre Singapore.

Discipline:

Medical Oncology

Scientific Interests:
  • Aspirin as adjuvant therapy in established cancers
  • Adoptive T cell therapy and Dendritic cell vaccines in the treatment of solid tumors
  • Clinical Trial Design and Management
Declaration of Conflicts of Interest:

In the past 3 years, I have received consultant fees from Tessa Therapeutics, Aslan Pharmaceuticals, Novartis, and AstraZeneca.

I received grant support for investigator-initiated research from:

  • National Medical Research Council Singapore
  • Bayer AG

I hold shares in:  Roche, BMS, AstraZeneca, Incyte, Teva Pharmaceuticals, Trillium Therapeutics, Compugen, Arrowhead pharmaceuticals, Emergex, QuantumDx and Halozyme Therapeutics

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Badimon

Lina Badimon

Name
Lina Badimon BSc, PharmD, PhD, FESC, FAHA
Academic Affiliations:
Director of the Cardiovascular Science Program (ICCC) at the Hospital Santa Creu and San Pau, IIB-Sant Pau; CIBER CV. Director of the Cardiovascular Research Chair of the Autonomous University of Barcelona and Director of the UNESCO Chair in Biomedical Sciences Training and Research.
Discipline:
Pharmacology, Cardiovascular Disease
Scientific Interests:
Cardio-metabolic diseases, thrombosis, atherosclerosis and ischemic heart disease
Declaration of Conflicts of Interest:

I received consultant and speakers fees from Amgen, AstraZeneca, Bayer, Lilly and Sanofi.

    Return to Scientific Advisory Board
    Ge

    Junbo Ge

    Name

    Junbo Ge

    Ge Junbo, male, was born in Wulian, Shandong province on Nov. 8, 1962. He is the member of Chinese Academy of Sciences, professor and doctoral supervisor. He received his doctor’s degree of Medicine from German Mayence University in 1993 and now works as the director for Shanghai Institute of Cardiovascular Disease and the Center for Stem Cells and Tissue Engineering, Fudan University. He is also the designate chairman of the Cardiovascular Disease Branch of Chinese Medical Association, council member of the Cardiovascular Angiography and Interventions Association, international consultant of the American Heart Association. In Dec. 2013, he was appointed as the vice president of Tongji University.

    Prof. Ge has been engaged in clinical and scientific research work of cardiovascular disease since 1987, and his research area covers the pathogenesis of coronary heart disease, early diagnosis and treatment plan optimization.

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    Langley

    Ruth Langley

    Name
    Ruth Langley PhD, FRCP
    Academic Affiliations:
    Professor of Oncology and Clinical Trials, MRC Programme Leader and Chair of the Cancer Group, MRC Clinical Trials Unit at UCL, honorary consultant in medical oncology at the Brighton and Sussex University Hospital.
    Discipline:
    Medical oncologist; trialist
    Scientific Interests:
    • Aspirin
    • Gastro-oesophageal malignancy
    • Transdermal oestrogen in the treatment of prostate cancer
    • Trials methodology
    Declaration of Conflicts of Interest:
    Has received honorarium from Bayer
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    Chan

    Andrew T Chan

    Name
    Andrew T. Chan MD, MPH
    Academic Affiliations:
    Chief, Clinical and Translational Epidemiology Unit, Vice Chair, Division of Gastroenterology, Massachusetts General Hospital, Boston, Co-leader, Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, Boston.
    Discipline:
    Gastroenterology
    Scientific Interests:
    • The role of aspirin in the prevention of colorectal cancer and other cancers
    • The role of the gut microbiome in colorectal cancer and other chronic gastrointestinal diseases, including inflammatory bowel disease and diverticulitis
    • The role of diet and lifestyle in colorectal cancer and other chronic gastrointestinal cancers
    Declaration of Conflicts of Interest:

    AACR Honors Dr. Andrew T. Chan With 2019 AACR-Waun Ki Hong Award

    Click here to find the press release.

    I received consultant Bayer and Pfizer, Inc.

    I received grant support for investigator-initiated research from:

    • National Institutes of Health
    • National Cancer Institute
    • Crohn’s and Colitis Foundation
    • Bayer AG
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    Gaziano

    Mike Gaziano

    Name
    J Michael Gaziano MD, MPH
    Academic Affiliations:

    Professor of Medicine, Harvard Medical School; Chief Division of Aging, Brigham and Women’s Hospital; Director of Preventive Cardiology and Director of Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System.
    Discipline: Cardiology and Epidemiology

    Scientific Interests:
    I am a chronic disease epidemiologist with a particular interest in the roles that individual lifestyle choices (diet, exercise, smoking), metabolic factors (obesity, high cholesterol, and hypertension), and biochemical and genetic markers play on the risk of cardiovascular disease and other chronic illnesses. Also, of interest is the impact that vascular disease has on other organ systems, including cognitive dysfunction and renal disease. I have an interest in the design of large-scale trials and observational studies nested in large health care systems using big data analytic techniques.
    Declaration of Conflicts of Interest:

    I received consultant and speaker fees Bayer.

    I received grant support as a principal investigator or co-investigator for research from the VA, DOD, NIH, Merck and Kowa.

    Return to Scientific Advisory Board
    Pierre A Web Photo

    Pierre Amarenco

    Name

    Pierre Amarenco, MD, FAHA, FAAN

    Academic Affiliations:
    • Professor of Neurology at Paris-Diderot Sorbonne University 
    • Chairman of the Department of Neurology and Stroke Center; Bichat University Hospital
    • Co-Director INSERM Unit-698 “Clinical Research in Atherothrombosis”
    Discipline:

    Neurology and Vascular Neurology

    Scientific Interests:
    • Understanding and preventing stroke and vascular diseases
    • Clinical trials in prevention of vascular diseases
    • Carotid intima-media thickness studies
    • Lipid trials: prevention and therapeutic –protective- evaluation
    Declaration of Conflicts of Interest:

    N/A

    Return to Scientific Advisory Board
    CarloPatrono

    Carlo Patrono

    CHAIR
    Name
    Carlo Patrono MD, FESC, FRCP
    Academic Affiliations:
    Adjunct Professor of Pharmacology at the Catholic University School of Medicine in Rome (Italy) and at the Perelman School of Medicine of the University of Pennsylvania in Philadelphia (USA).
    Discipline:
    Clinical Pharmacology
    Scientific Interests:
    • Studying platelet activation and inhibition in diabetes mellitus
    • Studying platelet activation and inhibition in myeloproliferative neoplasms
    • Investigating the mechanism of action of low-dose aspirin in preventing colorectal cancer
    Declaration of Conflicts of Interest:

    I received consultant and speakers fees from Acticor Biotech,  Amgen,  Bayer, GlaxoSmithKline,  Tremeau,  Zambon.

    I received grant support for investigator-initiated research from:

    • AIFA (Italian Drug Agency)
    • Bayer AG
    • Cancer Research UK
    • European Commission, FP6 and FP7 Programmes

      Return to Scientific Advisory Board

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