Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection & Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

 Am J Med. 2021 Jan; 134(1): 16–22.

Published online 2020 Aug 7. doi: 10.1016/j.amjmed.2020.07.003

PMCID: PMC7410805

PMID: 32771461

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection

Peter A. McCullough, MD, MPH,^a,b,c,⁎ Ronan J. Kelly, MD,^a Gaetano Ruocco, MD,^d Edgar Lerma, MD,^e James Tumlin, MD,^f Kevin R. Wheelan, MD,^a,b,c Nevin Katz, MD,^g Norman E. Lepor, MD,^h Kris Vijay, MD,ⁱ Harvey Carter, MD,^j Bhupinder Singh, MD,^k Sean P. McCullough, BS,^l Brijesh K. Bhambi, MD,^m Alberto Palazzuoli, MD, PhD,ⁿ Gaetano M. De Ferrari, MD, PhD,^o Gregory P. Milligan, MD, MPH,^a Taimur Safder, MD, MPH,^a Kristen M. Tecson, PhD,^b Dee Dee Wang, MD,^p John E. McKinnon, MD,^p William W. O'Neill, MD,^p Marcus Zervos, MD,^p and Harvey A. Risch, MD, PhD^q

Abstract

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.

 

 Rev Cardiovasc Med. 2020 Dec 30;21(4):517-530. doi: 10.31083/j.rcm.2020.04.264.

Multifaceted highly targeted sequential multidrugtreatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

Peter A McCullough  ¹ , Paul E Alexander  ² , Robin Armstrong  ³ , Cristian Arvinte  ⁴ , Alan F Bain  ⁵ , Richard P Bartlett  ⁶ , Robert L Berkowitz  ⁷ , Andrew C Berry  ⁸ , Thomas J Borody  ⁹ , Joseph H Brewer  ¹⁰ , Adam M Brufsky  ¹¹ , Teryn Clarke  ¹² , Roland Derwand  ¹³ , Alieta Eck  ¹⁴ , John Eck  ¹⁴ , Richard A Eisner  ¹⁵ , George C Fareed  ¹⁶ , Angelina Farella  ¹⁷ , Silvia N S Fonseca  ¹⁸ , Charles E Geyer Jr  ¹⁹ , Russell S Gonnering  ²⁰ , Karladine E Graves  ²¹ , Kenneth B V Gross  ²² , Sabine Hazan  ²³ , Kristin S Held  ²⁴ , H Thomas Hight  ²⁵ , Stella Immanuel  ²⁶ , Michael M Jacobs  ²⁷ , Joseph A Ladapo  ²⁸ , Lionel H Lee  ²⁹ , John Littell  ³⁰ , Ivette Lozano  ³¹ , Harpal S Mangat  ³² , Ben Marble  ³³ , John E McKinnon  ³⁴ , Lee D Merritt  ³⁵ , Jane M Orient  ³⁶ , Ramin Oskoui  ³⁷ , Donald C Pompan  ³⁸ , Brian C Procter  ³⁹ , Chad Prodromos  ⁴⁰ , Juliana Cepelowicz Rajter  ⁴¹ , Jean-Jacques Rajter  ⁴¹ , C Venkata S Ram  ⁴² , Salete S Rios  ⁴³ , Harvey A Risch  ⁴⁴ , Michael J A Robb  ⁴⁵ , Molly Rutherford  ⁴⁶ , Martin Scholz  ⁴⁷ , Marilyn M Singleton  ⁴⁸ , James A Tumlin  ⁴⁹ , Brian M Tyson  ⁵⁰ , Richard G Urso  ⁵¹ , Kelly Victory  ⁵² , Elizabeth Lee Vliet  ⁵³ , Craig M Wax  ⁵⁴ , Alexandre G Wolkoff  ⁵⁵ , Vicki Wooll  ⁵⁶ , Vladimir Zelenko  ⁵⁷

 

Abstract

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.

REFERENCE:
The McCullough Report