Please wait a minute...
Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (4): 517-530     DOI: 10.31083/j.rcm.2020.04.264
Special Issue: Utilizing Technology in the COVID 19 era
Review Previous articles | Next articles
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Peter A. McCullough1, *(), Paul E. Alexander2, Robin Armstrong3, Cristian Arvinte4, Alan F. Bain5, Richard P. Bartlett6, Robert L. Berkowitz7, Andrew C. Berry8, Thomas J. Borody9, Joseph H. Brewer10, Adam M. Brufsky11, Teryn Clarke12, Roland Derwand13, Alieta Eck14, John Eck14, Richard A. Eisner15, George C. Fareed16, Angelina Farella17, Silvia N. S. Fonseca18, Charles E. Geyer, Jr.19, Russell S. Gonnering20, Karladine E. Graves21, Kenneth B. V. Gross22, Sabine Hazan23, Kristin S. Held24, H. Thomas Hight25, Stella Immanuel26, Michael M. Jacobs27, Joseph A. Ladapo28, Lionel H. Lee29, John Littell30, Ivette Lozano31, Harpal S. Mangat32, Ben Marble33, John E. McKinnon34, Lee D. Merritt35, Jane M. Orient36, Ramin Oskoui37, Donald C. Pompan38, Brian C. Procter39, Chad Prodromos40, Juliana Cepelowicz Rajter41, Jean-Jacques Rajter41, C. Venkata S. Ram42, Salete S. Rios43 , Harvey A. Risch44, Michael J. A. Robb45, Molly Rutherford46, Martin Scholz47, Marilyn M. Singleton48, James A. Tumlin49, Brian M. Tyson50, Richard G. Urso51, Kelly Victory52, Elizabeth Lee Vliet53, Craig M. Wax54, Alexandre G. Wolkoff55, Vicki Wooll56, Vladimir Zelenko57
1Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, 75226, TX, USA
2Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, L8S 4L8, Ontario, Canada
3Armstrong Medical Group, Texas City, 75510, TX, USA
4North Suburban Medical Center and Vibra Hospital, Thornton, 80229, Colorado, USA
5Chicago Health and Wellness Alliance, Chicago, 60603, IL, USA
6Recipient of the Texas HHS Meritorious Service Award, 78751, Texas, USA
7PianoPsych, LLC, Natick, 01760, MA, USA
8Division of Gastroenterology, Department of Medicine, Larkin Community Hospital, S. Miami, 33143, FL, USA
9Centre for Digestive Diseases, Five Dock, 2046, NSW, Australia
10Infectious Diseases, St. Luke's Hospital, Kansas City, 64111, MO, USA
11University of Pittsburgh, Department of Medicine, Pittsburgh, 15213, PA, USA
12Clarke Neurology, Newport Beach, 92660, CA, USA
13Alexion Pharma Germany GmbH, 80687, Munich, Germany
14Affordable Health, Inc., Piscataway, 08854, NJ, USA
15Eisner Laser Center, Macon, 31210, GA, USA
16Pioneers Medical Center, Brawley, 92227, CA, USA
17Privia Medical Group, Webster, 24510, TX, USA
18Hapvida HMO, Ribeirão Preto,14015-130, SP, Brazil
19Houston Methodist Cancer Center, Houston, 77030, TX, USA
20The Medical College Of Wisconsin, Milwaukee, 53226, WI, USA
21Personal Healthcare Network, Kansas City, 64116, MO, USA
22Fusion Clinical Multimedia, Inc., Philadelphia, 19019, PA, USA
23Ventura Clinical Trials, PROGENABIOME, Malibu Specialty Center, Ventura, 93003, CA, USA
24Stone Oak Ophthalmology, Immediate Past President, Association of American Physicians and Surgeons, San Antonio, 78258, TX , USA
25Cardiosound, Atlanta, 30342, GA, USA
26Rehoboth Medical Center, Houston, 77083, TX, USA
27Complex Primary Care Medicine, Pensacola, 32507, FL, USA
28University of California Los Angeles, Los Angeles, 90095, CA, USA
29Emergency Medicine, Phoenix, 85016, AZ, USA
30Family Medicine, Kissimmee, 34741, FL, USA
31Lozano Medical Clinic, Dallas, 75218, TX, USA
32Howard University College of Medicine, Mangat and Kaur, Inc., Germantown, 20876, MD, USA
33President, Pensacola Beach, 3256, FL, USA
34Department of Medicine, Henry Ford Hospital, Wayne State University School of Medicine, Detroit, 48202, MI, USA
35Orthopaedic and Spinal Surgery, Private Practice, Omaha, 68135, NE, USA
36Internal Medicine, Executive Director, Association of American Physicians and Surgeons, Tucson, 85716, AZ, USA
37Foxhall Cardiology, PC, Washington, 20016, DC, USA
38Orthopedic Surgery, Salinas, 93907, CA, USA
39McKinney Family Medicine, McKinney, 75070, TX, USA
40Illinois Sports Medicine and Orthopaedic Center, Glenville, 60025, IL, USA
41Pulmonary and Sleep Consultants, Ft. Lauderdale, 33316, FL, USA
42MediCiti Medical College, 500005, Hyderabad, India
43University of Brasília, Brasilia , 70910-900, DF, Brazil
44Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, 06510, CT, USA
45Robb Oto-Neurology Clinic, Phoenix, 85012, AZ, USA
46Bluegrass Family Wellness, Crestwood, 40014, KY, USA
47Heinrich Heine University, Düsseldorf, 40225, Germany
48Past Pres. Association of American Physicians and Surgeons, Tucson, 85716, AZ, USA
49NephroNet Clinical Trials Consortium, Buford, 30518, GA, USA
50All Valley Urgent Care, El Centro, 92243, CA, USA
51Houston Eye Associates, Houston, 77025, TX, USA
52Victory Health, LLC., 80487, Colorado, USA
53Vive Life Center, 85728, Arizona & Texas, USA
54Family Medicine, Mullica Hill, 08062, NJ, USA
55CMO Emergency Hapvida Saude, HMO, Fortaleza, 60140-061, CE, Brazil
56National Healthcare Coalition, Family Medicine, Eagle, 83616, ID, USA
57Affiliate Physician, Columbia University Irving Medical Center, New York City, 10032, NY, USA
Download:  PDF(774KB)  ( 30832 ) Full text   ( 6730 )
Export:  BibTeX | EndNote (RIS)      
The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.
Key words:  SARS-CoV-2      COVID-19      hospitalization      mortality      ambulatory treatment      anti-infective      anti-inflammatory      antiviral      corticosteroid      antiplatelet agent      anticoagulant      sequenced multidrug therapy     
Submitted:  28 November 2020      Revised:  08 December 2020      Accepted:  15 December 2020      Published:  30 December 2020     
None related.
*Corresponding Author(s):  Peter A. McCullough     E-mail:

Cite this article: 

Peter A. McCullough, Paul E. Alexander, Robin Armstrong, Cristian Arvinte, Alan F. Bain, Richard P. Bartlett, Robert L. Berkowitz, Andrew C. Berry, Thomas J. Borody, Joseph H. Brewer, Adam M. Brufsky, Teryn Clarke, Roland Derwand, Alieta Eck, John Eck, Richard A. Eisner, George C. Fareed, Angelina Farella, Silvia N. S. Fonseca, Charles E. Geyer Jr., Russell S. Gonnering, Karladine E. Graves, Kenneth B. V. Gross, Sabine Hazan, Kristin S. Held, H. Thomas Hight, Stella Immanuel, Michael M. Jacobs, Joseph A. Ladapo, Lionel H. Lee, John Littell, Ivette Lozano, Harpal S. Mangat, Ben Marble, John E. McKinnon, Lee D. Merritt, Jane M. Orient, Ramin Oskoui, Donald C. Pompan, Brian C. Procter, Chad Prodromos, Juliana Cepelowicz Rajter, Jean-Jacques Rajter, C. Venkata S. Ram, Salete S. Rios , Harvey A. Risch, Michael J. A. Robb, Molly Rutherford, Martin Scholz, Marilyn M. Singleton, James A. Tumlin, Brian M. Tyson, Richard G. Urso, Kelly Victory, Elizabeth Lee Vliet, Craig M. Wax, Alexandre G. Wolkoff, Vicki Wooll, Vladimir Zelenko. Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19). Reviews in Cardiovascular Medicine, 2020, 21(4): 517-530.

URL:     OR

[1] Ritu Thamman, Rajesh Janardhanan. Cardiac rehabilitation using telemedicine: the need for tele cardiac rehabilitation[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 497-500.
[2] Alexandru Burlacu, Radu Crisan-Dabija, Adrian Covic, Catalin Raiu, Ionut Mavrichi, Iolanda Valentina Popa, Manuel Lillo-Crespo. Pandemic lockdown, healthcare policies and human rights: integrating opposed views on COVID-19 public health mitigation measures[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 509-516.
[3] Jasjit S. Suri, Anudeep Puvvula, Misha Majhail, Mainak Biswas, Ankush D. Jamthikar, Luca Saba, Gavino Faa, Inder M. Singh, Ronald Oberleitner, Monika Turk, Saurabh Srivastava, Paramjit S. Chadha, Harman S. Suri, Amer M. Johri, Vijay Nambi, J Miguel Sanches , Narendra N. Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R. Laird, Arindam Bit, Gyan Pareek, Martin Miner, Antonella Balestrieri, Petros P. Sfikakis, George Tsoulfas, Athanasios Protogerou, Durga Prasanna Misra, Vikas Agarwal, George D. Kitas, Raghu Kolluri, Jagjit Teji, Michele Porcu, Mustafa Al-Maini, Ann Agbakoba, Meyypan Sockalingam, Ajit Sexena, Andrew Nicolaides, Aditya Sharma, Vijay Rathore, Vijay Viswanathan, Subbaram Naidu, Deepak L. Bhatt. Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 541-560.
[4] A. Verner Venegas-Vera, Gates B Colbert, Edgar V. Lerma. Positive and negative impact of social media in the COVID-19 era[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 561-564.
[5] Chia-Te Liao, Wei-Ting Chang, Wen-Liang Yu, Han Siong Toh. Management of acute cardiovascular events in patients with COVID-19[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 577-581.
[6] Gates B. Colbert, A. Verner Venegas-Vera, Edgar V. Lerma. Utility of telemedicine in the COVID-19 era[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 583-587.
[7] Brian C. Procter, Casey Ross, Vanessa Pickard, Erica Smith, Cortney Hanson, Peter A. McCullough. Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 611-614.
[8] Qi Yao, Jian Ni , Tong-Tong Hu, Zhu-Lan Cai, Jin-Hua Zhao, Qing-Wen Xie, Chen Liu,Qing-Qing Wu. Clinical characteristics and outcomes in coronavirus disease 2019 (COVID-19) patients with and without hypertension: a retrospective study[J]. Reviews in Cardiovascular Medicine, 2020, 21(4): 615-625.
[9] Yin-jun Mao, Hang Wang, Jian-xing Chen, Pin-fang Huang. Meta-analysis of medical management versus catheter ablation for atrial fibrillation[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 419-432.
[10] Niloofar Deravi, Mobina Fathi, Kimia Vakili, Shirin Yaghoobpoor, Marzieh Pirzadeh, Melika Mokhtari, Tara Fazel, Elahe Ahsan, Samad Ghaffari. SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 385-397.
[11] Ramesh K. Goyal, Jaseela Majeed, Rajiv Tonk, Mahaveer Dhobi, Bhoomika Patel, Kalicharan Sharma, Subbu Apparsundaram. Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 365-384.
[12] Jun Zhang, Kristen M. Tecson, Peter A. McCullough. Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 315-319.
[13] Jun Zhang, Peter A. McCullough, Kristen M. Tecson. Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 339-344.
[14] Allison Zimmerman, Dinesh Kalra. Usefulness of machine learning in COVID-19 for the detection and prognosis of cardiovascular complications[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 345-352.
[15] Ajay K. Mahenthiran, Ashorne K. Mahenthiran, Jo Mahenthiran. Cardiovascular system and COVID-19: manifestations and therapeutics[J]. Reviews in Cardiovascular Medicine, 2020, 21(3): 399-409.
[1] Eli M. Roth, Michael H. Davidson. PCSK9 Inhibitors: Mechanism of Action, Efficacy, and Safety[J]. Reviews in Cardiovascular Medicine, 2018, 19(S1): 31 -46 .
[2] Sandeep K. Krishnan, Norman E. Lepor. Acute and Chronic Cardiovascular Effects of Hyperkalemia: New Insights Into Prevention and Clinical Management[J]. Reviews in Cardiovascular Medicine, 2016, 17(S1): 9 -21 .
[3] Ibrahim Sidiqi, Patrick Alexander. Current Advances in Endovascular Therapy for Infrapopliteal Artery Disease[J]. Reviews in Cardiovascular Medicine, 2015, 16(1): 36 -50 .
[4] Prakash C. Deedwania. Management of Patients With Stable Angina and Type 2 Diabetes[J]. Reviews in Cardiovascular Medicine, 2015, 16(2): 105 -113 .
[5] Peter Shalit. Management of Dyslipidemia in Patients With Human Immunodeficiency Virus[J]. Reviews in Cardiovascular Medicine, 2014, 15(S1): 38 -46 .
[6] Sophie Mavrogeni, Fabrizio Cantini, Gerald M. Pohost. Systemic Vasculitis: An Underestimated Cause of Heart Failure—Assessment by Cardiovascular Magnetic Resonance[J]. Reviews in Cardiovascular Medicine, 2013, 14(1): 49 -55 .
[7] George L. Smith. Appropriate Use Criteria: The Gold Standard, or a Mechanism for the Derogation of Clinical Judgment?[J]. Reviews in Cardiovascular Medicine, 2011, 12(2): 105 .
[8] Prabhjot Singh Nijjar, Anoop Parameswaran, Aman M. Amanullah. Evaluation of Anomalous Aortic Origins of the Coronaries by 64-Slice Cardiac Computed Tomography[J]. Reviews in Cardiovascular Medicine, 2007, 8(3): 175 -181 .
[9] . SELF-ASSESSMENT POST-TEST[J]. Reviews in Cardiovascular Medicine, 2006, 7(S2): 51 -52 .
[10] Alice K. Jacobs. Gender Differences in Coronary Revascularization: Does Age Make a Difference?[J]. Reviews in Cardiovascular Medicine, 2004, 5(1): 68 -70 .