Front Line Covid-19 Critical Care Alliance
IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC© FLCCC Alliance · October 31, 2020

IVERMECTIN —A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC
Recently, a wave of negative results were published from trials on numerous COVID-19 therapies, essentially eliminating any role for remdesivir, hydroxychloroquine, lopinavir/ritonavir, interferon, convalescent plasma, tocilizumab,
and mono-clonal antibody therapy.1–6 One year on, the only therapy considered “proven” as an effective treatment inCOVID-19 are the use of corticosteroids in patients with moderate to severe illness.7
Since March 2020, our expert panel, the Front Line COVID-19 Critical Care Alliance (www.flccc.net) led by Professor
Paul Marik, has continuously reviewed the rapidly emerging basic science, translational, and clinical data in COVID-19
with the aim of ensuring that our MATH+ Hospital Treatment protocol both continuously evolves and stays current. Asof October 28th, 2020, based on the increasing and recently reported data from a number of published and unpublishedtrials, we have concluded that the drug Ivermectin, an anti-parasitic drug with increasingly well-known anti-viral8–16
and anti-inflammatory properties has demonstrated profound activity against COVID-19. Based on these data, wehave devised a new prophylaxis and early treatment protocol against COVID-19 which we have named the “I-MASK+”­protocol which we believe may serve as a global solution to the pandemic. The evidence base in support of this conclusion shows that Ivermectin:
1.

Inhibits SARS-CoV-2 replication, leading to absence of nearly all viral material by 48h in infected cell cultures17

2.

Prevents transmission and development of COVID-19 disease in household members of infected patients18,19

3.

Hastens recovery and prevents deterioration in patients with mild to moderate disease treated early after symptoms20–25

4. Hastens recovery and avoidance of ICU admission and death in hospitalized patients25,26
5.

Leads to striking reductions in case-fatality rates in regions with population-wide distribution and use27,28

Equally critical features of Ivermectin supporting its potential role as a global intervention are that it is FDA approved,
inexpensive, easily compounded, well-tolerated, and has an excellent safety profile and long history of use.29 Further,
the drug has an extended duration of activity, and would require as little as one dose a week as a prophylaxis agent, andfrom 4-6 doses over two days as a therapeutic agent. The data suggests that as little as one or two doses a week taken bya significant proportion of citizens may lead to population-wide protection and reduced transmission in a manner thatis easier to achieve, more effective, and less expensive than the still elusive and widely suspect vaccine.19
The above listed studies showing the physiologic impacts of Ivermectin therapy in COVID-19 are all referenced below.
One study deserves particular attention, posted on the pre-print server Researchgate earlier this month by Dr. JuanChamie which provides an analysis of large amounts of real-world epidemiologic data in support of Ivermectin as aneffective population-wide intervention in Peru.27
The study provides population mortality data among 8 regions in Peru before and after the decision of the Peruvian
Ministry of Health to recommend and initiate the widespread distribution of hundreds of thousands of doses of Ivermectin for the treatment of COVID-19 patients. Figure 1 below illustrates a dramatic, temporally associated reduction
in case fatality rates in patients over 60 after widespread distribution of ivermectin was initiated, a response seen in
multiple regions at different times in the pandemic corresponding to the varying dates of initiation of distribution ofIvermectin. By focusing solely on patients over 60, the analyses remove the potential confounding decreases in mortality that could be caused by an increase of infections in healthier, younger people.

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC

Figure 1 Excess of deaths/population & COVID-19 cases/population (on population older than 60)

Figure 2 Cases and deaths by country

Peru

Brazil

India

PolandTurkey

India

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC

In a corroboration of the data in Figure 1, our group pulled case counts and death rates from several countries including Peru from the highly cited Worldometer COVID-19 global data site.30 The data from Peru in Figure 2 above reflect
similar impacts, i.e. compared to the other countries which reveal a “mirrored” increase in deaths correlating with each“spike” of cases, in Peru, the large increase in case counts from early August to mid-September instead correlated with
first a plateau and then a steady decrease in deaths, even beginning during the massive spike, with death rates now
approaching pre-pandemic levels.
In a similar “natural experiment” in Brazil, several large cities made the decision to widely distribute “home treatmentkits” containing Ivermectin to its citizens, the city of Itajai offered ivermectin to the entire population (approx. 200,000)
and some 120,000 accepted. In May the large city of Macapa opted to treat patients with Ivermectin and Azithromycin,
targeting those at risk or who had contact with a possible carrier. The city of Natal with a population of 1 million had
recommended Ivermectin for COVID-19 treatment and also for prophylaxis of health staff; after initial legal resistance,
1 million doses were distributed.28
The data is for September 14 from the official Brazilian government site (https://covid.saude.gov.br/) and the nationalpress consortium, the table shows data mid-September compared to mid-August (most Ivermectin was administered­during July). The bolded regions below all had a major city with Ivermectin distribution, the other nearby regions did not.
Table 1 Change in death rates among neighboring regions in Brazil(bolded regions contained a major city that distributed Ivermectin to its citizens, the unbolded regions did not)Regionstate

Change in average deaths (%) previous
week compared to 2 weeks ago (A)Total COVID-19
related deaths

Deaths/100K

South

Santa Catarina
Paraná
Rio Grande do Sul

–36
–3
–5

2,529
3,823
4,055

35.6
35.3
33.4

North

Amapá
AmazonasPará

–75
–42
13678
3,892
6,344

80.2
93.9
73.7

North East

Rio Grande do Norte
Ceará
Paraíba–65

2,3158,666
2,627

66.0
95.1
65.4

62–30

Beyond the death rate reductions found above, case counts also were reduced in the cities compared to neighboring
ones without Ivermectin distribution as below:
Table 2 Case count decreases in Brazilian cities with ivermectin distribution programs(bolded cities distributed ivermectin, neighboring cities in same region without distribution programs listed below)
RegionConfirmed newcases/month

June

July

AugustPopulation 2020
(1000)% Augustvs. June/JulySouth

Itajaí
Chapecó

2123
1760

2854
1754

998
1405

223
224

40%
80%

North

MacapáAnanindeua

7966
1520

2481
1521

2370
1014

503
535

45%
67%

North EastNatalJoão Pessoa

9009
9437

7554
7963

1590
5384

890
817

19%
62%

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC

The country of Haiti presents another interesting case in that it has a national program to prevent lymphatic filariasis
in which it distributes ivermectin to 1.2 million people a year. In Figure 3, case counts and death rates in Haiti (middlesection) is compared to its neighbor the Dominican Republic as well as the United States.
From the CDC website about this program: “CDC and partners have been supporting Haiti to eliminate LF and, overthe past year, have dramatically increased the number of people in the capital of Port-au-Prince who have received
treatment, reaching an additional 600,000 people and achieving mass drug administration targets of 65% for the firsttime in more than five years. CDC experts worked on community-level planning to improve local engagement and drug
distribution, as well as real-time tracking to confirm drugs were reaching those in need.”
Figure 3 COVID-19 cases and deaths (per million habitants) in the Dominican Republic, Haiti and the USA

Similar population-wide decreases are also seen in Figure 4 below using data from Paraguay which demonstrate thatafter the government of the state of Alta Parana launched its ivermectin distribution “de-worming” program in e­ arly
September (apparently a guise to avoid reprimand from the National Ministry of Health which was against usingI­vermectin to treat coronavirus), they distributed 30,000 boxes of Ivermectin in early September. By October 15th, thegovernor declared there were very few cases left in the state.
The numerous randomized and observational trials cited above can also be looked at using meta-analysis. Using thistechnique, a consistent, reproducible, and summary mortality benefit is found among both the randomized and observational trials, wherein both sets of trials reach a high degree of statistical significance in favor of Ivermectin treatment
as seen in Figure 5.

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC

Figure 4 COVID-19 in Paraguay – most affected departments

Figure 5 Meta-analysis of Ivermectin clinical studies

In conclusion, based on the in-vitro, animal, clinical, and real-world epidemiologic evidence to date, we find that Ivermectin, due to its highly potent anti-viral and anti-inflammatory activity, should be considered a highly effective globalsolution to the COVID-19 pandemic, not only by drastically reducing transmission rates via its prophylaxis capability but

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC

also as a therapeutic intervention which can reduce both the morbidity and mortality among mild, moderate, and evensevere disease phases.

The Front Line Covid-19 Critical Care Alliance
Pierre Kory, MPA, MD, Associate Professor of Medicine, Aurora St. Luke’s Medical Center
G. Umberto Meduri MD, Professor of Medicine, University of Tennessee
Jose Iglesias, DO, Associate Professor of Medicine, Hackensack School of Medicine, Seton Hall
Joseph Varon, MD, Professor of Medicine, University of Texas Health Science Center
Keith Berkowitz, MD, Center for Balanced Health, New York
Howard Kornfeld, MD, Medical Director, Recovery Without Walls
Eivind Vinjevoll, MD Critical Care and Emergency Department Chief, Volda, Norway
Scott Mitchell, MRCS, Associate Specialist, Princess Elizabeth Hospital, Guernsey
Fred Wagshul, MD, Lung Center of America, Dayton, Ohio
Paul E. Marik, MD, Professor of Medicine, Eastern Virginia Medical School

I-MASK+ and MATH+In March, 2020, the Front Line Covid-19 Critical Care Alliance developed the MATH+ Hospital Treatment Protocol for
COVID-19, for use in the hospitalized patient, with an emphasis on early initiation — you will find our “Scientific Reviewof COVID-19 and MATH+”, a detailed explanation of the efficacy of the protocol, as well as the MATH+ protocol itself (inseveral languages) on www.flccc.net/math-hospital-treatment
In October, 2020, the FLCCC Alliance developed the I-MASK+ Prophylaxis & Early Out­patient Treatment Protocolfor COVID-19, centered around the use of Ivermectin — the I-MASK+ protocol can be downloaded from www.flccc.net/
flccc-ivermectin-protocol

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IVERMECTIN: A POTENTIAL GLOBAL SOLUTION TO THE COVID-19 PANDEMIC