Review of the Emerging Evidence Demonstrating the Efficacy of
Ivermectin in the Prophylaxis and Treatment of COVID-19
https://covid19criticalcare.com/wp-content/uploads/2022/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdfPierre Kory, MD1*, G. Umberto Meduri, MD2†, Jose Iglesias, DO3, Joseph Varon, MD4, Keith
Berkowitz, MD5, Howard Kornfeld, MD6, Eivind Vinjevoll, MD7, Scott Mitchell, MBChB8, Fred
Wagshul, MD9, Paul E. Marik, MD10
1 Front-Line Covid-19 Critical Care Alliance
2 Memphis VA Medical Center, Univ. of Tennessee Health Science Center, Memphis, TN
3 Hackensack School of Medicine, Seton Hall, NJ.
4 Chief of Critical Care at United Memorial Medical Center in Houston, TX
5 Center for Balanced Health, New York
6 Recovery Without Walls
7 Volda Hospital, Volda, Norway
8 Princess Elizabeth Hospital, Guernsey, UK
9 Lung Center of America, Dayton, Ohio
10 Eastern Virginia Medical School
AbstractIn March 2020, the Front Line COVID-19 Critical Care Alliance (FLCCC) was created and led by
Professor Paul E. Marik to continuously review the rapidly emerging basic science, translational, and
clinical data to develop a treatment protocol for COVID-19. The FLCCC then recently discovered that
ivermectin, an anti-parasitic medicine, has highly potent anti-viral and anti-inflammatory properties
against COVID-19. They then identified repeated, consistent, large magnitude improvements in clini-
cal outcomes in multiple, large, randomized and observational controlled trials in both prophylaxis
and treatment of COVID-19. Further, data showing impacts on population wide health outcomes have
resulted from multiple, large “natural experiments” that occurred when various city mayors and
regional health ministries within South American countries initiated “ivermectin distribution” cam-
paigns to their citizen populations in the hopes the drug would prove effective. The tight, reproducible,
temporally associated decreases in case counts and case fatality rates in each of those regions com-
pared to nearby regions without such campaigns, suggest that ivermectin may prove to be a global
solution to the pandemic. This was further evidenced by the recent incorporation of ivermectin as a
prophylaxis and treatment agent for COVID-19 in the national treatment guidelines of Belize,
Macedonia, and the state of Uttar Pradesh in Northern India, populated by 210 million people. To our
knowledge, the current review is the earliest to compile sufficient clinical data to demonstrate the
strong signal of therapeutic efficacy as it is based on numerous clinical trials in multiple disease
phases. One limitation is that half the controlled trials have been published in peer-reviewed publi-
cations, with the remainder taken from manuscripts uploaded to medicine pre-print servers. Although
it is now standard practice for trials data from pre-print servers to immediately influence therapeutic
practices during the pandemic, given the controversial therapeutics adopted as a result of this practice,
the FLCCC argues that it is imperative that our major national and international health care agencies
devote the necessary resources to more quickly validate these studies and confirm the major, positive
epidemiological impacts that have been recorded when ivermectin is widely distributed among
populations with a high incidence of COVID-19 infections.
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The FLCCC recommendation is based on the following set of conclusions derived from the existing
data, which will be comprehensively reviewed below:
1) Since 2012, multiple in vitro studies have demonstrated that Ivermectin inhibits the replication
of many viruses, including influenza, Zika, Dengue and others (Mastrangelo et al.,
2012;Wagstaff et al., 2012;Tay et al., 2013;Götz et al., 2016;Varghese et al., 2016;Atkinson et
al., 2018;Lv et al., 2018;King et al., 2020;Yang et al., 2020).
2) Ivermectin inhibits SARS-CoV-2 replication and binding to host tissue via several observed
and proposed mechanisms (Caly et al., 2020a).
3) Ivermectin has potent anti-inflammatory properties with in vitro data demonstrating profound
inhibition of both cytokine production and transcription of nuclear factor-κB (NF-κB), the
most potent mediator of inflammation (Zhang et al., 2008;Ci et al., 2009;Zhang et al., 2009).
4) Ivermectin significantly diminishes viral load and protects against organ damage in multiple
animal models when infected with SARS-CoV-2 or similar coronaviruses (Arevalo et al.,
2020;de Melo et al., 2020).
5) Ivermectin prevents transmission and development of COVID-19 disease in those exposed to
infected patients (Behera et al., 2020;Bernigaud et al., 2020;Carvallo et al., 2020b;Elgazzar et
al., 2020;Hellwig and Maia, 2020;Shouman, 2020).
6) Ivermectin hastens recovery and prevents deterioration in patients with mild to moderate
disease treated early after symptoms (Carvallo et al., 2020a;Elgazzar et al., 2020;Gorial et al.,
2020;Khan et al., 2020;Mahmud, 2020;Morgenstern et al., 2020;Robin et al., 2020).
7) Ivermectin hastens recovery and avoidance of ICU admission and death in hospitalized
patients (Elgazzar et al., 2020;Hashim et al., 2020;Khan et al., 2020;Niaee et al.,
2020;Portmann-Baracco et al., 2020;Rajter et al., 2020;Spoorthi V, 2020).
8) Ivermectin reduces mortality in critically ill patients with COVID-19 (Elgazzar et al.,
2020;Hashim et al., 2020;Rajter et al., 2020).
9) Ivermectin leads to striking reductions in case-fatality rates in regions with widespread use
(Chamie, 2020).5
10) The safety, availability, and cost of ivermectin is nearly unparalleled given its near nil drug
interactions along with only mild and rare side effects observed in almost 40 years of use and
billions of doses administered (Kircik et al., 2016).
11) The World Health Organization has long included ivermectin on its “List of Essential
Medicines”.
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It is the authors opinion, that based on the totality of these data, the use of ivermectin as a
prophylactic and early treatment option should receive an A-I level recommendation by the NIH in
support of use by the nation’s health care providers. When, or if, such a recommendation is issued, the
Front Line COVID-19 Critical Care Alliance has developed a prophylaxis and early treatment
protocol for COVID-19 (I-MASK+), centered around ivermectin combined with masking, social
distancing, hand hygiene, Vitamin D, Vitamin C, quercetin, melatonin, and zinc, with all components
known for either their anti-viral, anti-inflammatory, or preventive actions (Table 4). The I-MASK+
protocol suggests treatment approaches for prophylaxis of high-risk patients, post-exposure
prophylaxis of household members with COVID-19, and an early treatment approach for patients ill
with COVID-19.
