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, PhDq
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