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A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021]

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Abstract

Second part of the timeline covering a period from April 2021 to June 2021 *** Topics: WHO's role and its funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers issue, comparison to the H1N1 pandemic, new treatment protocols, causal modeling. *** Other parts: *** Part 0: https://www.researchgate.net/publication/348077948 *** Part 1: https://doi.org/10.13140/RG.2.2.13705.36966 *** Part 3: https://doi.org/10.13140/RG.2.2.23081.72805 *** Part 4: https://doi.org/10.13140/RG.2.2.26000.53767 *** Part 5: https://doi.org/10.13140/RG.2.2.35015.16807 *** Additional notes (Feb-Apr 2022): https://doi.org/10.13140/RG.2.2.24356.55682 ***
A continuation of a timeline of ivermectin-related events in the
COVID-19 pandemic
Mika Turkia
M.Sc., mika.turkia@alumni.helsinki.fi, June 30, 2021
Abstract
This review presents a continuation of a previous timeline that described ivermectin-related events in
the COVID-19 pandemic from April 2020 to the end of March 2021. The new timeline covers a period
from the beginning of April 2021 to the end of June 2021.
In April 2021, the US National Institutes of Health (NIH) announced a new, large clinical trial including
ivermectin, with an estimated study completion date in March 2023. A large national trial was also
announced in the Philippines, a 1,160-patient trial in the US, and another trial in Ireland.
Trial results published in the period resembled those of previous trials, not producing clinically meaningful
changes to the results of existing meta-analyses. Mainstream press of the high-income countries mostly
repeated the same arguments as in the previous period, including the warnings against ivermectin by the
European Medicine Agency (EMA) and the World Health Organization (WHO). The sparse and one-
sided coverage of ivermectin in the press appeared to result from a program called Trusted News Initiative
(TNI). The censorship practices of the social media companies, with policies disallowing expression of
views differing from the guidelines of the WHO, continued unchanged, apparently organized under a
program called International Fact-Checking Network (IFCN).
In contrast to the previous period – during which groups such as the Front Line COVID-19 Critical Care
Alliance (FLCCC) and the British Ivermectin Recommendation Development (BIRD) group attempted
to influence the decisions of government agencies – in this period these groups began to bypass the
agencies and turn directly to clinicians and the public. FLCCC also published two new protocols, I-
MASS for mass immunization, and I-RECOVER for long haul COVID-19 syndrome (LHCS), and a
review article which by the end of the period had reached a position in the top 120 of 18 million articles
tracked by Altmetric. The BIRD group organized two online conferences on ivermectin and published a
meta-analysis which had reached a position in the top 60, respectively.
One of the authors of the in vitro study that initiated the international interest in ivermectin explained
that due to, for example, lack of adaptive immune responses in the cell model, their study was unsuitable
for making conclusions about in vivo dosing in humans. A review described 20 mechanisms of action of
ivermectin in COVID-19.
The parties against and in favor of ivermectin remained in deeply conflicting positions, presenting op-
posite conclusions on the existing research. The WHO, along with regulatory agencies and national
governments of high-income countries, appeared to aim at preserving the value of existing investments
in vaccine and investigational therapeutics development, as well as questioning the efficacy and safety of
repurposed medicines.
Criticism towards excessive influence of Bill Gates in the WHO emerged during the period, as the
largest funder of the WHO appeared to be a group of vaccine promotion and intellectual property
rights enforcement oriented organizations founded by Gates. There was a noticeable centralization of
power, with the pandemic response largely directed by a few public-private partnerships working on
commercializable technologies.
Keywords: COVID-19, SARS-CoV-2, WHO, ivermectin
1
Introduction
Ivermectin is a multifaceted medication invented in collaboration between Japanese professor emeritus
Satoshi ¯
Omura from Kitasato University and US researcher William Campbell from Merck & Co/MSD
between 1973 and 1979 [1];[2]. Each of them received one quarter of the 2015 Nobel Prize in phys-
iology or medicine for their discoveries [3]. Ivermectin is best known as an antiparasitic agent, with
approximately four billion doses having been administered since 1981, predominantly in Africa. Merck &
Co/MSD’s patent expired in most countries in 1996, and ivermectin preparations are currently available
internationally from many sources, with the production cost of a single dose estimated to be less than
0.1 US dollars [4].
This article extends the timeline of ivermectin related-events described in a previous preprint available
in two versions, March 30, 2021 and April 3, 2021 [5];[6]. The latter preprint covered the period from
April 1, 2020 to March 31, 2021. This preprint extends the timeline to cover April–June 2021, as well as
adding a few earlier events. Some caveats of the review are described in the previous preprint. Due to
resource limitations, details of many developments are not covered in detail but only mentioned briefly,
and omissions have been unavoidable. The focus of this review entails the social, organizational, financial
and legal aspects of the situation with ivermectin, with less emphasis placed on presenting clinical trial
results and biomedical research.
Some of the main events in the previously covered period from April 2020 to March 2021 were an
Australian in vitro study which initiated the interest in ivermectin [7]. This was followed by adoption
of ivermectin in several South and Central American countries, the state of Uttar Pradesh in India, and
Bangladesh in the second and third quarter of 2020. In late October 2020, the Front Line COVID-19
Critical Care Alliance (FLCCC) published its ivermectin-based outpatient protocol called I-MASK+ [8];
[9];[10].
A month later, another group called CovidAnalysis begun publishing a meta-analysis of ivermectin
trials [11] and a list of ivermectin studies [12]. A main event in December 2020 was the US Senate
hearing of Pierre Kory of the FLCCC [13]. The hearing raised interest of Lawrie et al. and Bryant
et al. who produced additional meta-analyses [14];[15]. In conjunction, another group called British
Ivermectin Recommendation Development (BIRD) was founded.
Another main event was the introduction of a preprint of a Unitaid/WHO-funded meta-analysis by Hill
et al. [16]. Yet another notable event was the publication of an extensive review by a Japanese group
including the discoverer of avermectins, the Nobel prize winner Satoshi ¯
Omura [2];[17].
In the first quarter of 2021, ivermectin had been adopted in several additional countries including Slovakia
as the first European Union member country. However, in March 2021 both the European Medicine
Agency (EMA) and the World Health Organization (WHO) advised against the use of ivermectin except
in clinical trials, ignoring the various meta-analyses and the results of 26 existing randomized clinical
trials, in addition to a similar amount of observational trials and other studies.
The majority of indications and the safety of ivermectin have been described in the previous preprint [6].
In addition, in April 2021 ivermectin was found to effectively inhibit hepatitis E virus replica-
tion [18]. There is also a relatively large amount of research about the treatment of cancers with
ivermectin [19][20][21][22][23][24][25], including breast cancer [26][27][28][29][30][31][32], ovarian can-
cer [33][34][35][36][37][38][39], cervical cancer [40], oesophageal squamous cell carcinoma [41], renal can-
cer [42], glioma [43][44][45], nasopharyngeal carcinoma [46], melanoma [47][48], gastric cancer [49][50],
liver cancer [51] and leukemia [52][53] (list from [54]).
Recently, mass distribution of ivermectin has been studied for prophylaxis of malaria [55];[56];[57]. Iver-
mectin has also been found to promote wound healing partly through modulation of the inflammatory
process and the levels of transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth
factor (VEGF) [58]. Ivermectin has also been proposed for the treatment of autoimmune disorders [59].
¯
Omura has characterized ivermectin as “a panacea for resource-poor communities” [60]. Ivermectin has
also been said to “continue to surprise and excite scientists, offering more and more promise to help
improve global public health by treating a diverse range of diseases, with its unexpected potential as
2
an antibacterial, antiviral and anti-cancer agent being particularly extraordinary” [61]. Possible issues
include environmental toxicity [62];[63] and the emergence of ivermectin resistance [64].
April 2020
On April 16, Chaccour et al. stated that the recent findings warrant rapidly implemented controlled
clinical trials and these trials might open a new field of research on the potential use of avermectins as
antivirals but extreme due diligence and regulatory review were needed before testing ivermectin in severe
disease. They added that off-label and compassionate use required careful risk–benefit considerations,
especially in critically ill patients. The authors suggested trials on early treatment of uncomplicated,
low-risk patients [65].
On April 17, a member of the European Parliament asked about the amount of influence of Bill and
Melinda Gates Foundation in the WHO [66];[67].
On April 18, a news report described that in the Dominican Republic, pulmonologist Johnny Tavárez
Capellán had carried out an observational trial with 247 patients, observing a favorable response in all
cases, with no fatalities [68];[69].
On April 23, Honduras introduced Catracho, a COVID-19 treatment protocol created by Hondu-
ran doctors Óscar Díaz, Fernando Valerio and Miguel Sierra-Hoffman, consisting of colchicine, anti-
inflammatories, tocilizumab, ivermectin, anticoagulants, and hydroxychloroquine [70];[71];[72].
On April 29, an article by Villar et al. (including Meduri of the FLCCC) provided a rationale for prolonged
corticosteroid treatment in COVID-19 [73].
August 2020
On August 2, a news report in a Mexican newspaper described FLCCC’s MATH+ inpatient protocol [74].
On August 5, the New York Times wrote about a “civil war in some hospitals” as a result of disagreements
on how much freedom should front-line clinicians have in treating COVID-19 patients with unproven
drugs [75]. The article described a conflict over care of a patient involved in a clinical trial, where a
clinician was pressured by a head researcher to retain the patient following the trial protocol although
the clinician considered adhering to the protocol dangerous for the patient in a critical condition. In this
case, the researchers compared relying on the clinician’s judgment to “witchcraft”, insisting the clinician
follow the “evidence”. The head researcher mentioned his wife had, however, taken hydroxychloroquine
for COVID-19 and recovered. Regardless, the head researcher insisted it was essential to rely on research
and anything else was witchcraft.
Another researcher who had spent two weeks in one hospital commented that he was “distressed by
how quickly doctors were trying untested therapies outside clinical trials. ‘I mean, it felt like it wasn’t
even World War I medicine,’ he said. ‘It was almost like Civil War-level medicine’ ”. He added that he
knew his colleagues had been risking their lives, been overwhelmed by their clinical demands and had
no research to rely on but was nonetheless surprised to see many of them making decisions “based on
the sort of opinion or written protocol of one or a couple of people that was based on kind of nothing
that I could see, other than just, ‘This seems like a good idea’ ”. Pierre Kory of the FLCCC commented
that “it became like Republicans and Democrats . . . the two sides can’t talk to each other”. After a
6,000-patient trial indicated benefits from corticosteroids [76], one researcher described as a “research
purist” commented that the efficacy “is still unknown” and that even one stellar randomized controlled
trial does not settle the question of the use of steroids for patients with Covid-19 as “it needs to be
replicated”. Kory commented that “that’s a 6,000-person trial he’s discrediting .. . that’s a person who
will never be convinced”.
The article also described the editor of the New England Journal of Medicine commenting that the
FLCCC’s recommendation of corticosteroids in the MATH+ inpatient protocol [77];[10];[9] used since
January 2020 and made publicly available in the first quarter of 2020 had been just “lucky”. He had
opposed corticosteroids but had eventually admitted he had been wrong, yet was still frustrated that
3
doctors were still relying on treatments for which there was no evidence. He had been more positive
about tocilizumab for which much less information than that for corticosteroids had been available. He
eventually concluded that “I know I seem to be saying opposite things . . . I can’t argue that I was super
rational either”.
On August 14, a commentary by Doidge discussed RCT fundamentalism in medicine [78]. He said “the
core belief [that only RCTs can decide] is repeated, like a catechism, at times ad nauseam, and contrasting
beliefs are treated like heresies. What the RCT fundamentalist is peddling is not a scientific attitude,
but rather forcing a tool, the RCT, which was designed for a particular kind of problem to become
the only tool we use. In this case, RCT is best understood as standing not for Randomized Control
Trials, but rather Rigidly Constrained Thinking”. Doidge concluded that “the most prudent option is
to allow the professional who knows the patient to have as much flexibility as possible and access to
as many medications as possible. If we are to be honest, evidence-based medicine is, in large part, still
aspirational. It is an ideal. Clinicians need latitude, and patients assume they have it. But now the
RCT fundamentalists are using the absence of RCTs for some drugs to restrict access to them. They
have gone too far. This is epistemological hubris, at the expense of lives, and brings to mind the old
adage, ‘Absence of evidence is not evidence of absence’. As long as we’ve not got the best studies for all
conceivable permutations, medicine will remain both an art and a science”.
September 2020
On September 28, a press release about Catracho, the treatment protocol of Honduras, reported that after
the introduction of Catracho on April 23, 2020 the hospital mortality rate had decreased from 14.5%
to 2.7% by the end of July, 2020 [70];[71];[72]. One of the creators of the protocol, Sierra-Hoffman,
stated that “I am proud that we can tell the world that Honduras has become part of contemporary
world history with golden letters.. . we have given the world an answer on how to address the virus in
critically ill patients, lowering mortality in Honduras, a country with many limitations and with one of
the worst prognoses when the pandemic begun . . . from a scientific point of view it is a great merit and
achievement for humanity”. The president of Honduras congratulated the team.
On September 29, a news report from the Dominican Republic described that Dr. José Natalio Redondo
had treated at least 6,000 outpatients with ivermectin with promising results [79]. He pointed out the
importance of initiating the treatment early.
October 2020
On October 13, Magro et al. published an article describing COVID-19 as a multifaceted viral vasculo-
pathy syndrome [80];[81]. They described that “each of the cytokines (IL-6, TNF-α, IL-1β, IL-8, and
p38) were significantly increased in the endothelia of select extrapulmonary microvascular beds where
they each strongly co-localized with the viral spike protein and ACE-2 receptors including the skin”. An
earlier 2008 study by Zhang et al. [82] had found that “ivermectin improved mouse survival rate induced
by a lethal dose of lipopolysaccharides. In addition, ivermectin significantly decreased the production of
TNF-α, IL-1ß and IL-6 in vivo and in vitro”, matching with the findings of Magro et al.
On October 20, in a video news report, Michael Jacobs, a clinical director of infection in Royal Free
Hospital in London, also a co-senior author of WHO’s living guideline for COVID-19 therapeutics and
an ivermectin panel member responsible for WHO’s ivermectin guideline [83], presented the hospital’s
trial in which volunteers were deliberately exposed to coronavirus in a controlled setting to speed up the
development of a successful vaccine [84].
On October 22, Portmann-Baracco et al. commented that “COVID-19 is divided into different phases:
asymptomatic, mild symptomatic disease, and severe inflammatory respiratory disease. The first two
phases are dependent on viral replication, whereas the latter is attributed to the hyper-inflammatory
state called the cytokine storm. Evidence suggests that ivermectin can act at different stages of the
disease. Controlled studies must be conducted first to demonstrate the effect of ivermectin against Covid-
19, then to determine if this effect is due to its antiviral action and finally to study if its administration
is convenient also in hospitalized patients due to its apparent anti-inflammatory effect” [85].
4
November 2020
An editorial by Abbasi in the British Medical Journal (BMJ) discussed politicization, “corruption” and
suppression of science in the context of COVID-19 pandemic [86]. According to the author, the pandemic
had unleashed state corruption on a grand scale, with politicians, industry, scientists and health experts
participating in an “opportunistic embezzlement” to manipulate the medical-political complex. As ex-
amples, the author listed lack of transparency, inappropriate involvement of government advisers in a
scientific advisory group, blocking of publication of findings about inadequacy of antibody tests, attemp-
ted blocking of a press release of a research paper, competing interests such as shareholding in companies
manufacturing tests, treatments and vaccines, and cherry-picking of science to advance anticompetitive
practices. The author stated that “suppressing science, whether by delaying publication, cherry picking
favorable research, or gagging scientists, is a danger to public health, causing deaths by exposing peo-
ple to unsafe or ineffective interventions and preventing them from benefiting from better ones. When
entangled with commercial decisions it is also maladministration of taxpayers’ money. Politicization of
science was enthusiastically deployed by some of history’s worst autocrats and dictators, and it is now
regrettably commonplace in democracies. The medical-political complex tends towards suppression of
science to aggrandize and enrich those in power. And as the powerful become more successful, richer,
and further intoxicated with power, the inconvenient truths of science are suppressed. When good science
is suppressed, people die”.
January 2021
On January 9, a newspaper in Peru reported that the former head of state Martín Vizcarra had recom-
mended the use of ivermectin as prevention and treatment despite the absence of scientific evidence,
saying that “it does work .. . ask those who have had the virus and were treated promptly with ivermec-
tin: the symptoms immediately decreased” [87]. The article mentioned opposition by the US FDA and
an analysis of possible therapies carried out by the Pan American Health Organization (PAHO) that had
concluded that studies on ivermectin presented “a high risk of bias, very little certainty of the evidence,
and that the existing evidence is insufficient to reach a conclusion on its benefits and its damages” (in
2014, PAHO did not concern itself with damages from a mass distribution of ivermectin to 1.4 million
schoolchildren in Paraguay [88]). Regardless, local authorities had delivered ivermectin throughout sever-
al regions for months, but researchers from a social security scientific evidence generation department had
raised alarm about ivermectin’s ineffectiveness. The article finished with stating that “without having
taken all [opposing] arguments into account, Vizcarra finalized his recommendation as follows: ‘I am an
engineer, I am not a doctor, but I met with an expert committee which recommended mass distribution.
We have to resume prevention’ ”.
On January 27, Bill Gates said that the Coalition for Epidemic Preparedness Innovations (CEPI) had
helped fund a number of COVID-19 candidates including the Moderna and Oxford AstraZeneca vaccines,
that the United States had included USD 4 billion for Gavi in its latest COVID-19 relief package, and that
stopping the next pandemic will require spending tens of billions of dollars per year in for example mega-
diagnostic platforms which could test as much as 20 percent of the global population every week [89].
He said one of the most promising COVID-19 therapeutics were monoclonal antibodies which were
time-consuming to develop and manufacture. He also stressed the importance of new mRNA vaccines.
On January 29, Joel S. Hirschhorn published an ebook titled “Pandemic blunder: Fauci and public
health blocked early home COVID treatment” [90]. The author described the handling of the pandemic
as “criminally negligent homicide resulting from intentional actions by myriad government officials”. The
book concentrated on the actions of the US FDA and NIH. It also analyzed usefulness of RCTs, quoting
an article published in the New England Journal of Medicine written by former director of the US
Centers of Disease Control and Prevention (CDC) Thomas R. Frieden saying that “elevating RCTs at
the expense of other potentially highly valuable sources of data is counterproductive. A better approach
is to clarify the health outcome being sought and determine whether existing data are available that
can be rigorously and objectively evaluated, independently of or in comparison with data from RCTs, or
whether new studies (RCT or otherwise) are needed .. . there is no single, best approach to the study
of health interventions; clinical and public health decisions are almost always made with imperfect data
5
. . . there will always be an argument for more research and for better data, but waiting for more data
is often an implicit decision not to act or to act on the basis of past practice rather than best available
evidence. The goal must be actionable data – data that are sufficient for clinical and public health action
that have been derived openly and objectively and that enable us to say, ‘Here’s what we recommend and
why’ ” [91]. Hirschhorn added that “many researchers, like [Didier] Raoult [92], opted for observational
studies, in which as many patients as possible are treated. This is not a matter of choosing a design that
is ‘fatally flawed,’ it is a matter of choosing a design that is not unnecessarily fatal to the patients. It’s
not sloppiness (as some of his critics would allege), but being true to the study question as he saw it: how
can we save as many lives as possible. These observational studies could begin almost immediately, and
didn’t require the slow approval process that RCTs require”. Hirschorn also noted that “a study showed
that 35 percent of the conclusions of the finest RCTs, assessed by peer review and published in the most
respected medical journals, could not be replicated on reanalysis of their raw data. Meaning that when
researchers gave over their original data sets to another group, they could not come up with the same
results 35 percent of the time – in the very best, most-cited journals” [93].
February 2021
On February 5, Schellack et al. described the regulatory framework of South Africa, noting the December
22 decision against ivermectin and the January 27 decision to facilitate a controlled, compassionate access
program for it [94].
On February 9, an extension to ‘Together’ trial led by McMaster University was announced
(NCT04727424) [95];[96];[97];[98]. The evaluation of ivermectin was funded by Fast Grants, with
the overall trial infrastructure being supported by the Rainwater Foundation. The ivermectin arm was
apparently planned to be carried out in Brazil, with a single dose of 18 mg for participants weighing
40-60 kg and 24 mg for participants over 60 kg. The number of participants was expected to be up to
3,200, with results available within three to six months.
March 2021
On March 10, Kern et al. used pharmacokinetic modeling to investigate the dynamic impact of timing
and dosing regimens of ivermectin [99]. The authors noted that previous clinical trial results of other
drugs had been well explained by these models. In this study the greatest benefits were observed when
ivermectin was given immediately at the time of diagnosis. The authors wrote that even interventions
with minor antiviral effect may reduce host exposure if timed correctly. In contrast to other modeled
drugs for which no effect was observed, ivermectin seemed to be at least partially effective: given on
positivity, peak viral load dropped by 0.3-0.6 log units and exposure by 8.8-22.3%.
On March 10, Tarazona et al. prospectively assessed environmental of COVID-19 therapeutic solutions,
modeling scenarios for predicting levels of pharmaceuticals ending up in the environment through was-
tewater treatment plants. Their models predicted a very high impact for ivermectin and azithromycin,
even at use levels well below the default value of 1% of the population. The authors said the results
highlighted fish sublethal effects as the most sensitive target [100].
On March 12, Czech Republic extended the use of ivermectin from hospitals to all general practitioners
and distribution to all pharmacies [101]. For hospitalized patients, a dose of 0.2 mg/kg on days 1, 3 and
5 was administered, with a maximum daily dose of 24 mg. For outpatients, it was administered on days
1 and 3.
On March 16, a Czech newspaper wrote an article clearing “five misunderstandings” about ivermectin,
namely that 100 times the standard dosage would be needed, that ivermectin would damage liver and
kidneys, that the JAMA study was reliable, that ivermectin was for horses, and that there were no studies
about it [102].
On March 16, the National Institutes of Health ACTIV-6 announced a request for implementors for an
ACTIV-6 trial of repurposed medicines [103].
6
On March 16, a news story described some of the background of the adoption of ivermectin in South
Africa [104]. A lawyer involved in the process described the compassionate access programme “quite a
bureaucratic process, frustrating and completely unworkable” but said the government had agreed to
register ivermectin for the treatment of COVID-19 in the next few days, which the lawyer called “a
major breakthrough”.
On March 16, an article by Thaldar reported that the South African Health Products Regulatory Autho-
rity (SAHPRA) had failed to comply with a court order given on February 2, 2021, and therefore broken
the law [105]. This had resulted in ivermectin not having been distributed to COVID-19 patients.
On March 23, Michal Rezek, a head of cardioangiology clinic in the Czech Republic, commented that
he “does not understand the campaign against ivermectin”, most recently demonstrated by the European
Medicine Agency’s (EMA) decision against it [106]. Rezek said that for the time being, his hospital was
continuing its use. In the news report, Rezek refuted EMA’s arguments against ivermectin.
On March 23, a group of Brazilian medical associations demanded that drugs with no proven efficacy
against COVID-19 should be banned, recommending social distancing and hand washing instead [107].
On March 27, the head of the intensive care unit professor Nathi Mdladla in South Africa said that
ivermectin was widely utilized during the first wave. During the second wave in late 2020, authorities
noticed this practice and clamped down on it, threatening doctors who had been prescribing it with
sanctions. Mdladla believed this response had been unhelpful, and the case was going to appear in
a hearing at a high court. Professor Salim Abdool Karim, one of the doctors leading South Africa’s
coronavirus response, said that the doses being given to people could even be toxic and that “it must
be clearly stated that ivermectin does not kill the virus at dosages humans can tolerate. The amount of
drug needed to kill the virus is toxic to humans. Whatever it is doing, it is not killing the virus” [108].
On March 27, a Czech expert on clinical studies, Šimon Reich, said that doctors believe in new drugs
rather than decades-old antiparasics, and he didn’t understand why people were afraid to use old drugs
for new diseases [109].
On March 28, a group of British scientists and medical doctors, Health Advisory and Recovery Team
(HART), urged the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to consider
granting approval for ivermectin [110].
On March 29, Olufemi Emmanuel Babalola, who had organized an ivermectin RCT in Nigeria in May
2020 [111], was interviewed about the use of ivermectin in Nigeria [112]. Babalola stated that for
Nigeria’s population of 210 million inhabitants, there had been only 2,000 deaths, or 10 deaths per
a million inhabitants. In comparison, for France’s population of 65.4 million inhabitants and 108,000
deaths, the ratio was 1,650 deaths per a million inhabitants, i.e. over 160 times higher. Nigeria was said
to have had a special history with ivermectin due to it having been used for a very long time for the
treatment of onchocerciasis (river blindness). More ivermectin had likely been used in Nigeria than in
any other country in the world. Babalola claimed the reason for ivermectin not being used in Europe
was industry influence and ivermectin’s unprofitability in comparison to investigational pharmaceuticals.
Babalola claimed Merck & Co/MSD had pressured Nigeria’s government not to use ivermectin [113].
On March 30, Wehbe et al. discussed molecular aspects and therapeutic possibilities of repurposing
ivermectin for COVID-19 [114].
April 2021
On April 1, an article by Mourya et al. about a retrospective 100-patient trial in India suggested 89%
lower risk of no virological cure (10% vs 94%, RR 0.11, p<0.001) [115];[116].
On April 1, a feature by Wadvalla in the BMJ discussed division of the medical community in South
Africa [117]. The article described that a lobby group “South Africa Has A Right To Ivermectin” formed on
Facebook on January 2, 2021 had reached 72,000 members and was sharing information black market or
veterinary ivermectin, reportedly running “an awareness campaign for ‘the people’s medicine’”, physically
distributing pamphlets on the benefits of ivermectin at public spaces throughout the country.
7
On April 1, a Philippines House of Representatives hearing on March 29 about ivermectin was made
available online [118];[119].
On April 1, a news report by Horowitz pointed out that data by the WHO indicated a 81% reduction in
mortality due to ivermectin, yet the WHO recommended against using it [120].
On April 2, a news report by TrialSite News discussed allegations of scientific misconduct related to the
recent Unitaid/WHO funded meta-analysis by Hill et al. [121];[16]. The question was about whether or
not a third party not named as an investigator had modified or influenced it to downplay ivermectin’s
efficacy. The report said a French group, Bon Sens, had sent a demand letter to the University of
Liverpool alleging scientific misconduct.
On April 3, an interview of Morteza Shakhsi Niaee, the main researcher in an Iranian clinical trial on
ivermectin, discussed the current situation in Iran [122];[123];[124]. Niaee stated that “considering the
data and the risk-benefit ratio we should spread the word [about ivermectin’s efficacy] as much as we can
because it is our moral and public responsibility . . . we don’t know what the result [of this advocacy]
will be . . . [but] we hope to have a positive influence in the world”.
On April 4, Whiteboard Doctor discussed the ivermectin review published on March 24, 2021 by a
Japanese group including the discoverer of ivermectin Satoshi ¯
Omura [125];[2].
On April 4, a news report by ABC News suggested that unregulated self-medication with a combination
of medications or ivermectin had resulted in cases of liver damage in Brazil [126].
On April 4, Daily Mail (UK) wrote that Britain’s Health Secretary Matt Hancock was setting up an
anti-virals task force to produce a “new innovative coronavirus treatments” with one goal to develop a pill
suitable for early outpatient treatment, with details expected to be announced in the coming weeks [127];
[128]. Earlier in February 2021, Hancock had been found guilty of unlawful hiding of information about
COVID-19 related government spending [129]. The judge called the act “a historic failure”. The anti-
virals task force was said to attempt to turn “the latest research on anti-viral therapeutics into approved
medical treatments for coronavirus within months”. The report referred to UK’s “success of the vaccine
program” saying it “wants to replicate those achievements with anti-viral drugs”. The team was said to
be led by a “biochemist turned venture capitalist” Kate Bingham who had previously helped the UK
secure agreements for access to 357 million doses of six different vaccines. In 2020, Bingham had served
as the Chair of the UK vaccine task force and was currently sitting on the boards of six biotechnology
companies [130];[131].
On April 5, in response to a Brazilian physics professor claiming the meta-analyses produced by the
CovidAnalysis group were a scam, a blog post in Portuguese investigated the reliability of them [132].
The author noted that some of the world’s most published physicians and researchers had quoted the
results of the meta-analyses as valid. A mathematics professor interviewed for the post did not find
immediate methodological issues with the meta-analysis. The author had also been in contact with the
CovidAnalysis group directly.
On April 6, a news report indicated that after a juridical process the South African Health Products
Regulatory Authority (SAHPRA) and parties in favor of using ivermectin for COVID-19 had reached
an agreement, according to which registered medical practitioners may prescribe ivermectin for COVID-
19 [133].
On April 6, a news report from the Czech Republic mentioned an ongoing observational trial with 100
patients [134]. Asked about the difference between the ivermectin policy of the Czech Republic and the
EMA’s advice against ivermectin, a head of cardioangiology clinic Michal Rezek commented that the
contents of EMA’s detailed report were incompatible with the short statement published on the Inter-
net. Rezek said that while EMA admitted the existence of ivermectin studies with positive results they
said conclusions could not be made due to ivermectin having been part of a combination of drugs or that
the trials had had methodological deficiencies. Rezek said these were just “formal reservations” and that
“for them, positive studies are not enough to prove efficacy”. Rezek added that EMA’s recommendation
against ivermectin was not indicated by their not commonly available extensive scientific study. In this
background document, EMA rejected positive studies due to their various shortcomings but also stated
8
that the drug was safe and its efficacy could not be ruled out. Rezek said that “there is no evidence that
it did not work”.
On April 6, Syed stated that 54 of his previous YouTube videos mentioning ivermectin had been de-
monetized, and if he would mention ivermectin in his future videos they would be either removed or
demonetized [135].
On April 6, an article about a retrospective cohort study by Mokhtari et al. (n=28,759) concluded
that early outpatient treatment of mild COVID-19 with hydroxychloroquine (7,295 treated vs 21,464 not
treated) reduced the odds of hospitalization by 35.3% (7.2% vs 11.1%, p<0.001) and mortality by 69.7%
(0.4% vs 1.3%, p<0.001) in a six-month follow-up, with no adverse effects [136];[137].
On April 7, an interview of Tess Lawrie discussed the meta-analysis by Bryant et al. and the meta-
analysis by WHO, comparing the two [138];[15];[139]. Lawrie mentioned she had not found a protocol
for WHO’s review. She mentioned discrepancy between which trials had been classified as high risk and
low risk of bias.
On April 7, a preprint from Wiseman and Kory discussed the methodology of the clinical trial of Lopez-
Medina et al. and concluded that possible clustering and/or drug switching confounding obscured up to
56% of ivermectin’s effect [140];[141];[142].
On April 7, FLCCC weekly update discussed the situation in Zimbabwe, interviewing Jackie Stone who
said ivermectin had “completely changed the landscape for us” with an approximately ten-fold reduction
in mortality [143]. Stone had successfully been using colloidal silver, ivermectin and doxycycline protocol
for severely hypoxic patients, allowing patients with oxygen saturations under 80% to be treated at home
instead of being hospitalized [144]. According to Stone, the components complemented each other. Stone
had first been accused of malpractice but later, on January 28, 2021, Zimbabwe had approved ivermectin
nationwide [145];[146];[147][148][149]. The presentation detailed the various mechanisms of action of
ivermectin in each phase of COVID-19, including the role of CD147 receptor [143].
On April 8, an Italian pharmaceutical website updated its guidance on how to legally prescribe ivermectin
for COVID-19 in Italy [150].
On April 8, a preprint by Tsegay et al. indicated that ivermectin inhibited 89% of SARS-CoV-2 spike
protein binding to ACE2 [151].
On April 8, a statement by the FLCCC Alliance discussed disappointments related to vaccines, sug-
gesting these indicate an increased need for a medication such as ivermectin which has shown efficacy
comparable to vaccines [152]. The statement mentioned adoption of ivermectin in several countries and
cities including India, Japan and Mexico City, adding that the WHO and NIH have all the data they
need to recommend ivermectin to prevent and treat COVID-19.
On April 8, the Washington Post wrote about increased interest in ivermectin in the US, warning that the
use of veterinary formulations without knowledge of proper dosing may easily lead to overdosing [153].
A virologist stated that “to my knowledge, there is no data that suggests [ivermectin] is good for Covid-
19”. The article also mentioned Merck & Co/MSD’s statement against ivermectin [154], and a similar
statement by the Infectious Diseases Society of America [155]. Next, the article mentioned Kory’s
argument of ivermectin being a “miracle drug” and his opposition to waiting for data from more trials.
The article then discussed the US National Institutes of Health’s plan for a large-scale trial of repurposed
drugs (possibly including ivermectin, fluvoxamine and famotidine), saying this trial could give a definitive
answer to the controversy around ivermectin. Finally, the article mentioned “cautious optimism” raised
by the meta-analysis by Hill et al. [16].
On April 8, an editorial in the Wall Street Journal, referring to removals of material describing opinions
and actions of elected representatives and their advisers, stated “it’s chilling that Google’s YouTube,
through its ‘medical misinformation policy,’ appears to be systematically undermining the ability to
access material in the public interest” [156].
On April 9, FLCCC Alliance criticized the Washington Post story about not presenting the research
data about ivermectin’s effectiveness and not discussing the consequences of the prohibitive approach by
the government agencies and the censorship of science [157].
9
On April 9, a US news article titled “Scientists work toward an elusive dream: a simple pill to treat
Covid-19” discussed the possibility of a pharmaceutical for early outpatient treatment of COVID-19,
stating that the reason for it not existing yet “is not for lack of trying” [158]. The article included an
interview of the US National Institutes of Health director Francis Collins who called this kind of pill a
“dream”, adding that “it’s just a damn long pathway . . . but I will tell you that this is an extremely high
priority for Tony Fauci and Francis Collins and the Biden administration, to work with these companies
to try to make sure that we speed this up”. Pharmaceuticals in development by Merck & Co/MSD and
Ridgeback Biotherapeutics (molnupiravir), Atea Pharmaceuticals (AT-527) and Pfizer (PF-07321332)
were mentioned.
On April 9, a news report wrote that a State Supreme Court in New York, US had ordered a hospital
to administer four additional doses of ivermectin to a ventilated patient [159].
On April 9, Garcia et al. published a protocol for a randomized clinical trial comparing ivermectin to
placebo in early treatment in Peru (SAINT-Peru, NCT04635943) [160].
On April 10, an article about an in silico analysis by Bello found that the in vitro activity of ivermectin
may explained by acting as an inhibitor of importin-α, dimeric 3C-like protease, and Nsp9 [161];[162].
On April 11, the Wall Street Journal published an opinion by Johnson et al., the organizer of US Senate
hearings in late 2020 [163]. The authors stated there is already evidence for generics reducing COVID-19
mortality.
On April 11, Evidence-Based Medicine Consultancy Ltd (E-BMC), the research company behind the
meta-analyses of Lawrie et al. and Bryant et al., announced that YouTube had blocked video uploads
to the company’s account until July 10, 2021 [164].
On April 11, an interview of Mary Beth Pfeiffer, an investigative journalist and a contributor to Scientific
American, discussed censorship of ivermectin news [165];[166]. She said the current practices were
social media platforms’ attempt to be good citizens, and largely a response to the manipulation of
social media during the US presidential elections of 2016 which brought on calls of social media to
police itself or be regulated. Ironically, however, in this case efforts had backfired. She said there
had been “an extremely limited and unfair coverage” of ivermectin in the US and that the during her
forty years in journalism, never before had she encountered such censorship. In her opinion, since the
beginning of the hydroxychloroquine controversy involving president Trump there had been a bias in
the media against early treatment, leading the mainstream media to become very unwilling to conduct
proper investigation and act as journalists were supposed to, instead publishing superficial, erroneous
articles. Pfeiffer called for a major congress-led investigation on how the pandemic has been handled
in the US but added she was not confident there would be anyone able to conduct it properly. She
suggested courts as a good starting point for these investigations and demands. Another journalist,
Mariam Mia, described the atmosphere surrounding ivermectin journalism being characterized by fear. A
South African journalist, Viasen Soobramoney, described they had become unable to publish their stories
on social media platforms, leading them to realize the power of these platforms, noting it could lead to
scary scenarios. In the discussion it was mentioned that in South Africa, 700 medical doctors had joined
together to demand adoption of ivermectin and succeeded.
On April 11, the parliament of Italy voted in favor of early treatments [167].
On April 11, Bisoffi said that an interim analysis of an Italian trial (NCT04438850) had been performed
but the decision of the steering committee had been to continue the recruitment, leaving the researchers
blind as to the preliminary results (personal communication).
On April 11, a news report discussed the situation in Slovakia, noting that after the official authorization,
there was no central plan nor efficient market apparatus in place to efficiently and effectively allocate
supplies of ivermectin [168]. Therefore, availability remained an issue, with some Austrian pharmacies
said to have turned predatory, marking up the prices. Perhaps 10,000 Slovakians were said to have been
treated with ivermectin. Mainstream press was said to avoid the topic or quote physicians with dismissive
positions referring to stances of EMA and WHO. Despite the national authorization, Facebook continued
to censor local discussions.
10
On April 12, an article by Saha et al. investigated the binding mechanism of ivermectin with the spike
protein of SARs-CoV-2 using three different computational modeling techniques, concluding that iver-
mectin can be a suitable inhibitor for SARS-CoV-2 to enter into the human cell through hACE2 [169].
On April 12, a news report from Indonesia indicated that the government was finalizing its evaluation
of ivermectin [170].
On April 12, a news report from Lucknow, Uttar Pradesh, India stated that Indian states had simply
ignored the WHO recommendation against ivermectin [171].
On April 12, a medical doctor suggested that the ivermectin strategy of the pharmaceutical industry was
similar to the earlier strategy of the tobacco industry in denying the harms of smoking [172];[173];[174].
The author seemed to suggest that the Surgisphere scandal would have been a part of these strategies to
resist introduction of early treatments with repurposed medicines. He also seemed to suggest that the
WHO, NIH and FDA were involved in these delaying operations.
On April 12, a German magazine Bild wrote about the ivermectin controversy and the refusal of European
and German approval authorities to adopt ivermectin, quoting a German immunologist Peter Schleicher
saying “it is completely incomprehensible that there is no approval for this in Germany. We would have
thousands fewer deaths to mourn” [175].
On April 12, a news report wrote that ivermectin was going to be trialed in Ireland as a part of an
international Remap-Cap study [176]. It had already been administered to some critically ill patients
before the trial.
On April 12, New Republic published a news report by Zaitchik, titled “How Bill Gates impeded global ac-
cess to Covid vaccines” [177]. According to Zaitchik, Gates was using his foundation to defend monopoly
medicine. Initially in February 2020, a WHO expert group had drafted outlines for pandemic response,
assuming that the world would unite against the virus and that intellectual property issues would not
be allowed to slow things down. In May 2020, WHO Covid-19 Technology Access Pool (C-TAP) was
launched. However in March 2020, Gates had first launched Therapeutics Accelerator, a joint initiative
with MasterCard and Wellcome Trust, then in April 2020 a larger initiative inside the WHO called
Access to COVID-19 Tools Accelerator (ACT-Accelerator), which was a a public-private partnership
based on charity and industry enticements. According to Zaitchik, it “enshrined Gates’s long-standing
commitment to respecting exclusive intellectual property claims .. . [the idea that intellectual property]
must be protected, even during a pandemic, carried the enormous weight of Gates’s reputation as a
wise, beneficent, and prophetic leader . . . technically housed within the WHO, the ACT-Accelerator is
a Gates operation, top to bottom”. It included a vaccine arm called COVID-19 Vaccines Global Access
(COVAX) which aimed at providing a small amount of vaccines to low-and-middle-income countries for
a lower price [178]. Zaitchik wrote that Gates actively sought to undermine all challenges to his au-
thority and ACT-Accelerator’s intellectual property–based charity agenda. Pharmaceutical companies,
through International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), strongly
supported Gates. C-TAP was manipulatively sidelined in favor of ACT-Accelerator/COVAX which later
completely failed to meet its stated goals. Gates also prevented Oxford University’s plan to place the
rights to its vaccine candidate in the public domain. Subsequently, the rights were sold to Astra Zeneca.
On April 13, an open letter by US doctors described the ivermectin trial by López-Medina et al. published
in JAMA on March 4, 2021 as “fatally flawed” [179];[141].
On April 13, a preprint by Al Sulaiman et al. of a multicenter, non-interventional, retrospective cohort
study of 738 critically ill patients at ICUs found a significant association between thiamine use with
in-hospital mortality (OR 0.49, 95% CI 0.25-0.97, p=0.04) as well with 30-day ICU mortality (OR 0.45,
95% CI 0.22-0.94, p=0.03). Thiamine also reduced the likelihood to for thrombosis by 81% (OR 0.19,
95% CI 0.04-0.88, p=0.034) [180]. Thiamine is a central component of the FLCCC Alliance’s MATH+
hospital treatment protocol [10].
On April 13, Sky News report claimed that the WHO had tried to force a former WHO employee to
change a key report to hide the fact that Italy had not updated its pandemic response protocols since
2006 [181]. The employee said the affair has completely undermined WHO’s reputation, adding that
“I think the problem here is about lack of independence and lack of transparency of the WHO. The
11
mandate of the organization is to preserve and to promote the health of the entire world. The story that
happened shows that the organization is bound by personal interests, government interests, and financial
powers”. The news report said WHO had refused to help Italian prosecutors investigating Italy’s COVID-
19 planning, even stating its staff members had immunity from questioning, leaving the prosecution team
confused and suspicious. The team said WHO was turning the investigation “into something political”.
On April 14, a prophylaxis study in Singapore by Seet et al. indicated that for low-risk patients, a
single dose of 0.2 mg/kg (max 12 mg) indicated 49.8% lower risk of severe case compared to vitamin C
administration (RR 0.50, p=0.01, n=1,236) (NCT04446104) [182];[183].
On April 15, website Science-Based Medicine wrote that ivermectin was the new hydroxychloroquine
and there was no evidence it could treat COVID-19 [184].
On April 15, at the Medscape website, Vega discussed whether ivermectin or fluvoxamine should be
used for outpatients, mentioning studies indicating reduction in mortality in hospitalized patients but
no difference in outpatients (in the JAMA study), concluding that the was no indication for routine use
of ivermectin in COVID-19, adding that FDA and Merck & Co/MSD had advised against its use [185].
The author was more positive about fluvoxamine for outpatients but concluded that more studies were
needed.
On April 15, in Slovakia, a head of intensive care Jakub Hložník described that they had found ivermectin
ineffective, stating that their experience confirms the negative opinions of international organizations and
the manufacturer [186]. He dismissed the prophylaxis studies done in India as invalid but added there was
one “real study published in the prestigious journal JAMA” indicating no effect, stating “this is the most
objective study” and that the criticism was about “these people blaming everything” and that in vitro,
ivermectin only acts at doses 100 times higher than approved for humans. About the medical profession,
he said that “we are not divided. There is a group of doctors who claim to have a cure for COVID-19,
and there are the rest of the doctors who are silent because they smile at it or think it is not worth
commenting on. We are not inconsistent: look at the opinions of professional companies in which world
experts examine how medicines work and what side effects they have”. He added that “an atmosphere
has been created in which anyone who tells the truth [about ivermectin’s ineffectiveness] is attacked
for not being able to heal the patients”. He said accusations of corruption had “transcended all bounds
of decency”. About cases, he commented that ivermectin “didn’t help at all. There were patients who
received ivermectin and then fought for their lives on the ventilator for several more weeks and recovered.
If I were like [the ivermectin proponents], I would go to the media and say it was due to ivermectin. But
the reality is that this drug did not work at all .. . some patients used it at home and ended up in our
hospital. If it were so effective, people would not end up with a severe COVID-19 in a hospital despite
taking it. That is common sense. You don’t need to be a doctor to understand that . . . I still don’t
understand why they attack us when our patients receive the same treatment as in other developed
countries .. . [allegations about a pharmaceutical lobby] are illogical, because if ivermectin took up,
it would become a gold mine for pharmaceutical companies. It would be used by tens or hundreds of
millions of people”. He said they were mainly using corticosteroids, heparin and vitamins C and D as a
supportive treatment, and had tested monoclonal antibodies. Ivermectin was unwise to use “because we
don’t know how the drug behaves in a COVID-19 patient receiving a number of other medicines” and they
had seen cases of ivermectin poisoning. He felt healthcare professionals were spreading misinformation
about ivermectin, and added that “it is strange that we have reached a state where ivermectin is being
distributed by mayors. It’s a prescription drug, not a lentil .. . it is a great paradox that people are
willing to eat medicines for horses and cattle, but do not want to be vaccinated”. The epidemic situation
was said to have “improved a bit, thanks to vaccinations and restrictions. But we may read again that it
was ivermectin”. He also did not believe in the alleged results of Michal Rezek in the Czech Republic.
On April 16, in the Czech Republic, a head of cardioangiology clinic Michal Rezek described that the
mortality rate of over one hundred ivermectin-treated inpatients had been around 10 percent, in contrast
to a general level of around 20 percent in the Czech Republic [187]. He said a small proportion of patients
do not respond to any treatment, and that ivermectin probably has a greater meaning and effect in the
outpatient setting and in the early stages of the disease. He said ivermectin is offered to almost everyone
in the hospital. He said they don’t have convincing results of other antivirals. He added that no-one
in the EU has applied for ivermectin’s approval for COVID-19 because in order to do that successfully
12
one would need a large trial with thousands of patients and such large investments are made mainly be
pharmaceutical companies expecting future profits. To the question of why ivermectin’s role is “desperate”,
he answered that “I don’t know, there are probably more factors .. . some doctors simply do not believe
in these positive results. Security risks are mentioned, although there is no evidence of harm. The US NIH
has stated that there are currently no clear arguments for or against. This is probably the most rational
opinion ever issued by an official large institution. They correctly stated that at present the evidence
for ivermectin is such that it cannot be clearly stated that it should be recommended because we lack
a large placebo-controlled study, but that it cannot be said that it should not be used due to relatively
numerous positive results reported in smaller studies”. About the WHO decision, Rezek commented that
for other medicines that the WHO had recommended against there had been large studies to back up
the decision, whereas for ivermectin there had not been such a study. In this respect, the handling of
ivermectin had been a deviation from the previous practices. Rezek also mentioned Satoshi Omura had
“argued quite convincingly ivermectin should be used and that the data are already sufficient”. About
COVID-19 in general, Rezek said that “the problem is that we still don’t understand the course of the
disease: it behaves completely differently from other viral diseases”.
On April 16, a scoping review by Bhowmick et al. concluded that evidence is not sufficiently strong
to either promote or refute the efficacy of ivermectin, doxycycline, or their combination in COVID-19
management [188]. There were no new safety signals of concern. The quality of studies was said to vary
widely, with five studies having a “good” methodological quality [189];[190];[191];[192] and two studies
having a “fair” quality [193];[194].
On April 16, an article by Molento described “unprecedented consequences in Latin America” [195]. The
author said endo- and ectoparasites had developed a strong tolerance to ivermectin since the 1980s with
increasing reports in the last two decades. The recent COVID-19-related widespread self-medication was
said to have been adopted based on false promises against any medical, pharmacological and epidemiolo-
gical recommendations. The article stated that ivermectin distribution did not result in any modification
in the shape of COVID-19 curves when comparing groups of treated and untreated people from the same
area, adding that ivermectin might have contributed to a terrible situation in Manaus, with allegedly
90% of patients admitted to the ICU having taken ivermectin as prophylaxis. The author had not seen
sound evidence of efficacy and was opposed to communities being used as experimental units, adding that
a number of toxic effects had been observed “after 35 consecutive weeks of treatment or even with the
use of ten times the antiparasitic therapeutic dose, . . . [and] increasing numbers of IVM-related hepatitis
(12 cases in 3 months in the state of Bahia)”. The article added that livestock released approximately
15 tons of ivermectin per year from fecal elimination in Brazil with an unmeasurable ecotoxicity impact,
and assumed that human intake of ivermectin could have a significant additional negative impact to
ground water and city reservoirs. The article also noted deficiencies in the individual studies on which
the meta-analysis of the CovidAnalysis group was based on. The author concluded that “in Brazil, the use
of ivermectin is being regarded as a political fanaticism, which could be punished by international tribu-
nal . . . we must condemn its illegitimate and fabricated prescription. Moreover, we should pay attention
to the WHO’s safety measurements to minimize the virus circulation, and advocate mass vaccination to
safeguard the entire region”.
On April 16, an opinion published in the Wall Street Journal [196] said: “how shocking it is to read in your
editorial that YouTube’s standard for medical misinformation is information that contradicts authorities
[156]. Modern medicine doesn’t believe in authorities but in evidence based on data analyzed from
randomized controlled studies. We must never allow anonymous censors to determine what is medical
misinformation and cancel scientific inquiry and discussion with which they disagree”.
On April 17, a retrospective cohort study by Morgenstern et al. indicated 74.0% lower risk of infection
(RR 0.26, p=0.008, n=542) [197];[198].
On April 17, an open-label nonrandomized case study with 10 ivermectin-treated patients and 15 controls
in a French care home suggested (results not statistically significant) 70.0% lower risk of death (10.0% vs
33.3%, RR 0.30, p=0.34) and 55% lower risk of severe disease (30.0% vs 66.7%, RR 0.45, p=0.11) [199];
[200].
On April 17, a presentation by FLCCC’s Marik focused on methylprednisolone and ivermectin [201].
13
On April 18, Salaamedia published a discussion about censorship of science with E. V. Rapiti, Tess
Lawrie and Pierre Kory [202].
On April 18, an article by Domingo-Echaburu et al. discussed ivermectin’s ecotoxicity [62]. They wrote
that available risk assessments confirm extremely high toxicity for invertebrates and that the use of
wastewater treatment plant sludge as soil fertilizer in agricultural soils should be approached cautiously.
On April 19, the National Institutes of Health (NIH) announced ACTIV-6 trial intended to compare
up to seven repurposed medicines in outpatients with mild to moderate COVID-19 [203];[103]. It was
not announced which medicines would be included in the trial and the trial was not yet registered. The
NIH had granted USD 155 million funding for the trial. Enrollment was said to begin in the summer
of 2021. The participants were to have had symptoms for no more than seven days. The changes in
symptoms were to be assessed over a 14-day period, as well as any hospitalizations and deaths over a
28-day period. Long-term post-COVID-19 symptoms were to be assessed at 90 days.
On April 19, Vanderbilt University Medical Center announced it had been named Data Coordinating
Center (DCC) for the ACTIV-6 trial [204].
On April 19, Jackie Stone described in an interview that in Zimbabwe, a group of doctors started
ivermectin administration on August 8, 2020. She described that seven previously critical patients and
one patient in palliative care suddenly recovered and mortality of her patients dropped to zero [205];
[206]. After two weeks, one 22-bed hospital had become empty. Since the end of August, the information
spread on social media. A second wave emerged in January 2021. Official authorization for ivermectin
for COVID-19 was granted on January 26, 2021, and by February 26, 2021, COVID-19 mortality in
Zimbabwe had dropped to zero.
On April 19, a review by DiNicolantonio et al. suggested that the effectiveness of ivermectin in the
cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by
increased activation of glycine receptors on leukocytes and possibly vascular endothelium [207];[208].
On April 19, Sky News of Australia reported on ivermectin research, interviewing an Australian par-
liament member Craig Kelly and showing a recorded statement by Tess Lawrie [209]. Lawrie addressed
doctors who had taken the Hippocratic oath, saying they had sworn to do the very best for their patients
and that ivermectin was the only thing treating COVID-19 at all stages. She said she had evaluated the
evidence properly but for some reason the health authorities had not, asking the doctors to evaluate the
evidence themselves. Craig Kelly commented that for over six months he had been “abused and ridiculed”
for trying to bring up exactly the same things Lawrie had just stated. The interviewer cited the comment
by Peter Schleicher [175] and a statement by professor Robert Clancy saying Kelly had been right to raise
awareness about ivermectin and hydroxychloroquine and that due to limitations of vaccines they need to
be paired with effective, safe drug treatment [210];[211];[212]. Kelly said the national decision against
ivermectin was based on eleven studies. Kelly referred to the CovidAnalysis group’s meta-analysis, saying
50 of 51 studies indicated “high” efficacy of ivermectin, adding that “bureaucrats had refused to look at
the evidence”. The report also referred to March 22 article in an UK pharmacy magazine saying “in the
UK, the best way forward would be for the MHRA to authorize use of ivermectin for prophylaxis and
treatment of Covid-19 on the basis of the published evidence to date” [213]. The report also cited Yale
professor Alessandro Santin stating that “ivermectin works . . . we must find a way to administer it on a
large scale to a lot of people” [214]. Kelly said twelve studies on prophylaxis showed that ivermectin had
“close to 90% efficacy which is actually equal or superior to vaccines .. . it is the people who are pushing
the vaccines who for some reason want to suppress the treatment with ivermectin . . . millions of people
are dead because of this”. The interviewer commented that “there is a lot of dishonesty at work here .. .
this is frightening, this is disgusting”.
On April 19, Frohman et al. published an article about the importance of early treatment, writing
that “one very painful outcome of this past year of the pandemic experience is that there has been
almost a complete lack of management of those with mild and moderate disease, as well as those wholly
asymptomatic. Unfortunately, it is during this initial time, the initial assessment where patients have
been summarily told to ‘go home and not return until you are more sick’, that may represent a time
when they are beyond our capability to nurse them back to health, or even to save their lives” [215]. The
authors also presented a new early treatment protocol that however did not include ivermectin.
14
On April 19, a report discussed politicization of ivermectin, mentioning lack of availability of remdesivir
and vaccines in resource-limited settings, adoption of ivermectin in Slovakia, the Czech Republic and parts
of Latin America, the warnings of FDA, EMA, Merck & Co/MSD and EMA, pro-ivermectin campaign
in South Africa, pressure to adopt ivermectin in the Philippines, and the Surgisphere scandal [216].
The author concluded that “consequences of global healthcare inequality are clear: if life-saving vaccines
aren’t available, people will be driven to take matters into their own hands – with potentially catastrophic
results”.
On April 20, a news report in the Guardian discussed the new UK antiviral task force, reviewing six
medicines (dexamethasone, tocilizumab, budesonide, favipiravir, remdesivir, convalescent plasma) having
“shown promise in treating Covid” [217]. Ivermectin was not mentioned.
On April 20, Cochrane Collaboration published a protocol for a systematic review about ivermectin for
preventing and treating COVID-19 [218].
On April 21, the State Institute for Drug Control of the Czech Republic was threatening a Czech
newspaper with a fine of approximately USD 25,000 for illegal advertising of ivermectin’s efficacy by
publishing stories with a claim assigned to Paul E. Marik that ivermectin reduced mortality or a claim
assigned to Michael Rezek that Czech inpatients had been improved by ivermectin treatment [219]. The
threat was described as “shocking” and illegitimate by some parliament members who also accused the
Ministry of Health of reluctance in easing patients’ access to ivermectin [220].
On April 21, the FLCCC Weekly Update discussed “the WHO’s denial of ivermectin: ‘Big Science’, dis-
information and their impacts on human rights”, in which “Big Science” represented a concept similar
to “Big Pharma” [221]. Kory described how the FLCCC recommendations with regard to COVID-19
had consistently been months to a year ahead of recommendations of other entities, and now wanted to
discuss “what we as a group are now finding with our advocacy of good evidence-based medicine: we are
now what I think is actually beyond the science. We are running to an area which I knew little about
before Covid happened and which I’m quickly becoming an expert on”. He said “the WHO most clearly
demonstrate what we are up against”. According to him, the FLCCC had been accused of spreading
misinformation (advocacy of “unproven therapies”). Kory introduced the concept of disinformation to
describe the practices of, among others, the WHO. He noted the converging expert opinions from the
UK (the BIRD group [222];[15]), Japan [2], UNITAID/WHO [16] and Spain, in contrast to the oppo-
sing recommendations issued by agencies including the European Medicine Agency (EMA), SAHPRA
and CADTH. He said the FLCCC had tried to pursue data-based arguments with these organizations
but it had been futile. Initially, the FLCCC had assumed the barrier was the “Big Science”, a societal
constellation that requires that treatments are proven by large RCTs, the fact that only large agencies or
pharmaceutical companies are able to finance trials of this magnitude, and premium journals publishing
results of these trials and ignoring small clinician-initiated trials, resulting in a monopolization of “se-
rious” science to large, well-funded actors only. Recently in the case of ivermectin, however, the FLCCC
had changed its view, no longer seeing the “Big Science” as the only barrier with regard to resistance to-
wards ivermectin. Instead, a more prominent barrier appeared to be a targeted disinformation campaign
against ivermectin specifically, pursued predominantly through the WHO.
On corticosteroids, Kory said most hospitals were still adhering to WHO’s guidance based on University
of Oxford’s Recovery dexamethasone trial [76]. According to Kory, it was “an anemic dose” of wrong
corticosteroid (FLCCC had recommended methylprednisolone since March 2020). Another mistake had
been a dismissal of the role of organizing pneumonia first described in a February 14, 2020 article by
Wu et al. [223]. After several rejections, Kory had eventually managed to publish an article on the issue
in the BMJ on September 22, 2020 [224]. Later the concept had begun to gain more attention [225];
[226]. He also mentioned the FLCCC had recognized the role of airborne transmission and the roles of
vitamins C, D, melatonin, statins, etc., early on in 2020 (in the MATH+ inpatient protocol). In addition,
the phase-based nature of COVID-19 had not been recognized [227].
Kory mentioned the US NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (AC-
TIV) public-private partnership program [228]. According to Kory, one of the partners, the Bill and
Melinda Gates foundation, had “an overwhelming policy of global vaccination” and “they essentially re-
present vaccine manufacturers”. ACTIV program had organized six trials on therapeutics [229]. ACTIV-
I, had included three patent-protected pharmaceuticals, ACTIV-II ten investigative pharmaceuticals,
15
ACTIV-III six investigative pharmaceuticals, ACTIV-4 four antithrombotics including aspirin and he-
parins, ACTIV-5 two investigative monoclonal antibodies, and ACTIV-6 ivermectin. In addition, there
had been NIH-funded studies on, for example, remdesivir and convalescent plasma.
On disinformation, Kory said that commonly used tactics included conducting counterfeit science and
trying to pass it off as legitimate research, harrassing scientists, manufacturing uncertainty where little
or none exists, buying credibility through alliances with academia or professional societies, and ma-
nipulating government officials or processes to influence policy. As examples, he mentioned: Merck &
Co/MSD obscuring the risks of rofecoxib [230] and GlaxoSmithKline trying to silence a scientist resear-
ching the safety of rosiglitazone [231], both of which were later withdrawn from the market; the US opioid
crisis having been created or exacerbated by webs of influence woven by several pharmaceutical companies
involving health professionals, patient advocacy groups, medical professional societies, research universi-
ties, teaching hospitals, public health agencies, policymakers and legislators [232]; Pfizer pressuring FDA
to downplay the risks of roxarsone [233]; counterfeit science on the safety of asbestos [234]; tobacco in-
dustry practices [235] and a few other examples. About WHO’s past track record, Kory commented that
“that was then, this is now” and that most of the budget now “has strings attached .. . [WHO is] a very
compromized organization particularly susceptible to external influences”, especially the Bill and Melinda
Gates Foundation through Gavi The Vaccine Alliance, CEPI and COVAX. Also, the “revolving door”
phenomena was said to have a large effect. According to Kory, the recent failures of the WHO included
handling of the Chernobyl (1986) and Fukushima (2011) nuclear disasters, the Ebola epidemic in 2014,
the H1N1 pandemic in 2009-2010, and the COVID-19 pandemic. On ivermectin’s evidence base, Kory
said WHO had failed to publish a pre-established protocol for data exclusion, excluded trials from their
original Unitaid search protocol, excluded two quasi-randomized RCTs with lower mortality, two RCTs in
which ivermectin was combined with other medications, seven other RCTs, all RCTs about prophylaxis,
13 observational trials with more than 5,500 patients, and numerous epidemiological studies.
Among possible interests against the adoption of ivermectin, Kory said, were in effect everything related
to investments in vaccines and investigative pharmaceuticals, including sovereign nations producing them,
with “the scale of the market almost incalculable”. In closing, Kory asked clinicians to “stop looking for
the public health agencies for guidelines . . . they don’t give expert guidance”. He added that it had
appeared that the WHO was “accountable to no-one and [for] nothing .. . there is no entity above the
WHO which can hold the WHO accountable .. . it’s a bizarre entity .. . I don’t know how to fix the
WHO . . . many people have tried in the last 20 years”, adding that one way might be to disallow any
voluntary contributions.
On April 22, FLCCC’s article published as a preprint in 2020 [236], provisionally accepted to Frontiers
of Pharmacology, peer-reviewed but subsequently retracted post-peer-review [237];[238];[239], was
published in American Journal of Therapeutics [240].
On April 22, Philippe Duneton, the chief of Unitaid, the sponsor of the meta-analysis by Hill et al. [16];
[241], said there was a need to “double down on research and development for COVID-19 treatment” [242].
In March 2021, Hill had allegedly said Unitaid had forced him to alter the conclusion of his meta-analysis
to state that more research is needed, instead of stating that ivermectin should be adopted based on the
current evidence [243]. In the April 22 interview, Duneton said “I think that there is a need .. . not just
to look [at] old drugs, but to double down [on] the effort in terms of screening of potential new drugs . . .
people at the beginning thought that it was possible to repurpose drugs, so from hydroxychloroquine,
to ivermectin, to colchicine, to remdesivir. A long list. But .. . I think that we can say that we don’t
see a real opportunity with old drugs . . . except dexamethasone”. However, Unitaid was apparently still
including ivermectin in its funded trials “to fill in the gap in evidence”. Duneton said “we need to finish
the job, because I think that we have seen that people, for whatever good reason, I suspect, want to use
drugs without evidence [of benefits]. That’s the situation. And I think it’s quite important to find out”.
Duneton was said to “hope for better outcomes for new antivirals in development, such molnupiravir,
which is being developed by Ridgeback Biotherapeutics and Merck & Co. and is advancing to Phase 3
trials for outpatient use, along with early-stage antivirals being developed by Pfizer”. He also hoped that
the second generation of monoclonal antibodies would be efficacious against the new COVID-19 variants
and would be easier to administer. Next, the report mentioned an agreement between the Bill and Melinda
Gates Foundation and Eli Lilly to develop a monoclonal antibody to treat COVID-19 in low- and middle-
income countries. The agreement was said to be a part of the COVID-19 Therapeutics Accelerator, which
16
worked with but was separate from the ACT Accelerator, of which Unitaid was part. Unitaid was said
to typically provide funding for late-stage research and development of new drugs and diagnostics and
to bring more affordable formulations to low-and-middle-income countries (LMICs), adding that those
efforts “had not been fully maximized”. Duneton explained that Unitaid and its partners were working
in parallel to ensure access for LMICs when and if new treatments prove to have a significant benefit.
“So what kind of incentive, how we can push [for access in LMICs?] Can we organize volume guarantees
[the way] we did, for example, for the rapid tests with the Gates Foundation, or incentivize generic
manufacturers so we can have access for LMICs in all continents? It’s a lot of money, but that’s the kind
of tool that we need to consider”, Duneton said.
On April 22, Indian Council of Medical Research COVID-19 National Task Force published clinical
guidance for management of adult COVID-19 patients [244]. For mild disease, as an option “based on low
certainty of evidence”, the guideline suggested 0.2 mg/kg ivermectin for three days, with the suggestion
to avoid it in pregnant and lactating women. For moderate and severe disease the guideline suggested
predominantly methylprednisolone and low molecular weight heparin.
On April 22, an opinion by Garegnani et al. stated that research related to ivermectin in COVID-19 has
serious methodological limitations resulting in very low certainty of the evidence, and continues to grow
[245].
On April 22, a post on the website of Gavi The Vaccine Alliance discussed why ivermectin isn’t re-
commended for use, mentioning the Surgisphere scandal, the case of rejection of FLCCC’s article by
Frontiers of Pharmacology, the EMA’s and NIH’s lack of support due to insufficient evidence, and the
ongoing Together trial co-sponsored by Bill and Melinda Gates Foundation [246]. The author concluded
that “it would therefore be premature to conclude absolutely that ivermectin has no place in COVID-19
treatment. On the basis of current evidence, however, its use cannot be recommended”.
On April 24, a full interview of Jackie Stone talking about ivermectin in Zimbabwe was made availa-
ble [247].
On April 24, Shankara Chetty from South Africa discussed alternative therapy options for COVID-19
[248]. In lymphatic filariasis, host inflammatory responses are due to dying microfilariae [249]. Chetty saw
a parallel to inflammatory responses in COVID-19, using ivermectin for immunomodulation of dyspnea
which he considered an allergic reaction in the lung due to virus particles [248]. He said there had been
no fatalities, no need for oxygenation and no cases of long haul COVID-19 syndrome among his 4,000
patients and that his method “has stood up to the test of time far better than vaccines would”. He said
in some countries medicine was very regulated with people taught to follow protocols and not to step out
of the box. Conversely in India doctors are taught to think outside the box, to try anything, to diagnose
patients with their clinical skills, and to only use diagnostic laboratory tests to verify or clarify their
clinical diagnosis, never to come to a diagnosis. He also referred to arrogance and snobbery, saying it
was difficult to convince someone when they are closed in their ways.
On April 24, a petition to the Government of Canada suggesting adoption of ivermectin for COVID-19
opened on March 25 ended with 4,825 signatures [250].
On April 24 and 25, the BIRD group organized the First International Ivermectin for Covid Confe-
rence [251]. The speakers included Mobeen Syed (US), Tess Lawrie (UK), Pierre Kory (US), Hector
Carvallo (Argentina), Juan Chamie (US), Andrew Bryant (UK), David Chesler (US), Eli Schwartz (Is-
rael), Wasif Khan (Bangladesh), Manjul Medhi (UK) and Matjaž Zwitter (Slovenia). Syed described five
mechanisms of action of ivermectin. Lawrie described the principles of assessment of research evidence,
the role of systematic reviews, details of the meta-analyses carried out by the BIRD group [222];[15] and
issues with WHO’s meta-analysis. Lawrie referred to the Hippocratic oath and the Helsinki Declaration
as fundamental rights of clinicians, adding that BIRD membership was intended for doctors in need of
peer support. Chamie compared changes in case fatality ratios of some countries before and after the
introduction of ivermectin. Bryant provided an overview of ongoing trials. Chesler described handling of
scabies and COVID-19 outbreaks in nursing homes in the United States involving 513 high-risk residents
with 309 confirmed COVID-19 cases treated with multi-drug approach (12 mg of ivermectin on days 1
and 8, doxycycline, azithromycin, enoxaparin, zinc, vitamins C and D).
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Schwarz described final results of their double-blinded RCT in Israel initiated in March 2020 to study
reduction of viral shedding in isolated non-pregnant adult outpatients with mild to moderate or asymp-
tomatic disease. Due to the massive vaccination campaign there was no longer a need for ivermectin treat-
ments in the population; nor, due to lack of patients, was it possible to continue ivermectin studies. Kory
discussed recent changes to FLCCC’s MATH+ inpatient protocol and the I-MASK+ prophylaxis and
early outpatient protocol. Khan described his ivermectin trial conducted in Bangladesh [252]. Carvallo
described his experience with ivermectin in long haul COVID-19 syndrome (LHCS). Peers described
LHCS as a mast cell activation issue [253]. Mehdi discussed ivermectin in patients at risk of dissemi-
nated strongyloides infection. Zwitter discussed medical ethics related to ivermectin in COVID-19.
On April 25, a cluster randomized trial about repurposing ivermectin for outpatients with a mild dis-
ease (IVER-Leve) sponsored by the Argentinian Ministry of Public Health completed in Argentina
(NCT04784481), indicating that a higher proportion of outpatient discharge was observed in treated
patients (98.2% vs 86.1%, p=0.0007) and that the treated patients showed eight times higher chance
of discharge (OR 8.71, 95% CI 1.99-38.12. p=0.004) even in the presence of comorbidities [254];[255];
[256];[257];[258]. The authors concluded that the treatment with ivermectin could significantly prevent
the evolution to serious stages since no treated patients deteriorated to a severe disease.
On April 25, an letter by Roche et al. stated that despite reported antiviral effects at supratherapeutic
doses in vitro, there is neither clinical evidence nor a plausible biologic mechanism to support ivermectin
as an effective prophylactic or therapeutic agent against SARS-CoV-2, and that it is important that
healthcare professionals understand the lack of evidence for its application to COVID-19, and continue
to refute and rebut misleading health information [259].
On April 26, an article about prophylaxis by Bartoszko et al., a group involved with WHO’s living
guideline, included one trial of ivermectin combined with iota-carrageenan (n=234) [260] and two trials
of ivermectin alone (n=540) [261],[262], all compared with standard of care or placebo. The authors
concluded that it was highly uncertain whether ivermectin combined with iota-carrageenan or ivermectin
alone reduced the risk of SARS-CoV-2 infection [263]. The authors noted that “the data are consistent
with three meta-analyses [264];[265];[16] and one network meta-analysis [266] evaluating ivermectin
as treatment for COVID-19. In contrast with other meta-analyses, we rated the certainty as very low
because of serious risk of bias and very serious imprecision”.
On April 26, a news report in a Canadian newspaper said Pfizer’s was testing its investigational drug
PF-07321332, developed from scratch during the current pandemic, which, if successful, could become
first-ever COVID-19 outpatient treatment [267]. Pfizer said it had demonstrated potent in vitro antiviral
activity against SARS-CoV-2 and it was soon going to be given to 60 volunteers in a phase I trial.
On April 27, the CEO of Pfizer said that an oral drug PF-07321332 for COVID-19 outpatients could
be ready by the end of the year 2021. Pfizer had begun an early-stage clinical trial of the oral drug in
March 2021. It was working on two antivirals, an oral and an injectable [268]. The report said the drug
“could become first-ever home cure for COVID-19 .. . for Pfizer and PF-07321332, it is a ‘race against
time’, [a professor in pharmaceutical medicine] said. They not only need to produce a drug that works
but need to do it while SARS-CoV- 2 still presents a major public health threat” [267].
On April 27, Merck & Co/MSD announced that it had entered into non-exclusive voluntary licensing
agreements for molnupiravir (EIDD-2801/MK-4482), an investigational oral therapeutic intended for
treatment of COVID-19 outpatients, with five established Indian generics manufacturers [269].
On April 27, YouTube removed FLCCC’s video “WHO’s denial of ivermectin: ‘Big Science’, disinforma-
tion and their impacts on human rights” [270].
On April 27, professor Salim Abdool Karim, one of the doctors leading South Africa’s coronavirus
response with a critical opinion about ivermectin, joined WHO’s science council [271].
On April 28 in the Philippines, two lawmakers were planning to distribute three doses of ivermectin at
no cost at an event in which those hoping to get ivermectin could present their medical prescriptions
or get a prescription from doctors present at the event. FDA director Eric Domingo commented that
he had no objection to the plan and that distribution of human-grade ivermectin was allowed as long
as it is made by a licensed compounding laboratory with a doctor’s prescription and the patients are
18
checked before issuing a prescription. He added FDA was not for or against any medicine and that it only
prohibited unregulated and unregistered drugs. A doctor estimated over 100,000 people were to be given
ivermectin over the next few weeks and regularly monitored afterwards. The Philippines Department of
Health maintained there was still no concrete evidence of efficacy in mild to moderate COVID-19 [272].
On April 28, an article in The Scientist by Offord discussed events subsequent to the retraction of
FLCCC’s ivermectin review by Frontiers of Pharmacology in the beginning of March 2021 [273]. The
review was intended to be a part of a special issue on drug repurposing for COVID-19, produced by
guest editors. Offord wrote that on April 23, following disagreements about other submissions and more
than a month of failed negotiations between Frontiers and the guest editors about how to proceed, the
editors had followed through on previous threats to resign, while the publisher pulled the special issue
page from its website. The editors stated that “the actions of Frontiers in this matter clearly violated
well established norms and processes for peer review and publication of scientific works and intellectual
contributions .. . in our opinion, these unfortunate events constitute gross editorial misconduct” [274].
On April 28, MedPage Today reviewed the history of the development of Merck & Co/MSD’s molnupi-
ravir (MK-4482/EIDD-2801) [275].
On April 29, a news report stated that the Christian Social Union in Bavaria (CSU) had called for the
federal government in Berlin to help with the adoption of ivermectin [276]. The proposal mentioned that
ivermectin had already been adopted in Slovakia as the first EU country, and that two expert groups at
the Robert Koch Institute already considered ivermectin a potentially active substance.
On April 30, version 66 of the CovidAnalysis group’s meta-analysis of ivermectin studies was made avail-
able [277]. 24 peer-reviewed RCTs and observational studies indicated 88% improvement for prophylaxis
(RR 0.15, 95% CI 0.05-0.30, n=6,356), 84% improvement for early treatment (RR 0.16, 95% CI 0.08-0.31,
n=882), 36% improvement for late treatment (RR 0.64, 95% CI 0.43-0.94, n=1,338), and 72% overall
improvement (RR 0.28, 95% CI 0.18-0.41, n=8,576).
On April 30, a preprint by Aguirre-Chang et al. described a therapeutic plan for patients with persistent
symptoms [278].
On April 30, an interview with parliamentary managing director of the CSU, Tobias Reiss, called for
the authorization of ivermectin in Germany [279]. Reiss mentioned that unlike in the Czech Republic,
ivermectin was not discussed in the German media. Reiss also said the FLCCC protocols which included
ivermectin were used with favorable results at the Academic Hospital Brothers of Mercy in Munich.
Reiss indicated he put more trust in the views of FLCCC, BIRD, and German and Czech scientists using
ivermectin than the guidance of EMA and Merck & Co/MSD. According to Reiss, German scientists
with experience on ivermectin had stated that “negative evaluations are not based on a thorough analysis
of the current state of knowledge”. Also Bernhard Seidenath, the chairman of the committee for health
and care in the Bavarian state parliament announced CSU had begun campaigning for ivermectin to be
trialed for COVID-19 in Germany [280].
In April, Bhorat et al. published a qualitative analysis of seven ivermectin formulations in South Africa
indicating that four out of seven formulations contained additional undeclared active pharmaceutical
ingredients such as paracetamol, dicyclomine, telmisartan, diclofenac, hydroxyzine, mebeverine, nor-
triptyline, ornidazole, pregabalin, clopidogrel and etizolam [281].
May 2021
On May 1, a medical doctor using a pseudonym Justus R. Hope published an ebook “Ivermectin for
the World” [282]. The book introduced pioneers of early treatments, including George Fareed’s, Harvey
Risch’s, Brian Tyson’s and Peter McCullough’s experiences with hydroxychloroquine, details of two US
Senate hearings about early treatments in 2020, interviews of Pierre Kory and Paul E. Marik, some
background of Andrew Hill’s meta-analysis, an article about José Natalio Redondo’s use of ivermectin
in the Dominican Republic, a statement by Jean-Jacques Rajter, articles about court proceedings about
ivermectin treatments in the US and in South Africa, an article about YouTube’s censorship practices,
an open letter and a statement by Lawrie, an article about India, and several other articles.
19
On May 3, an analysis of the results of early treatment with an ivermectin-based medical kit in Mexico
City by Merino et al. indicated a significantly lower hospitalization with ivermectin use, with approxi-
mately 70% lower risk of hospitalization [283];[284].
On May 4, a preprint by Karale et al. describing a systematic review and a meta-analysis of 30 studies in-
dicated an overall mortality benefit (OR 0.39, 95% CI 0.22-0.70) and an even more significant mortality
benefit in mild/moderate cases (OR 0.10, 95% CI 0.03-0.33) [285];[286].
On May 4, an article by Okumuş et al. (the preprint of which had been made available on January
12) about a randomized controlled trial (n=66) about late treatment in Turkey compared low dose
hydroxychloroquine, azithromycin and favipiravir with and without ivermectin, indicating 80% lower
risk of no virological cure (13% vs 63%, p=0.02) on day 10 (NCT04646109) [287];[288].
On May 4, MedPage Today discussed cases in the US in which judges had ordered hospitals to give
ivermectin to patients despite no evidence of efficacy and even though it wasn’t endorsed by federal
health agencies [289]. The story mentioned potential side effects of the drug include nausea, vomiting
and diarrhea, as well as facial or limb swelling, neurologic adverse events, a sudden drop in blood pressure,
and liver injury, according to the FDA, as well as FDA’s warning against the use of veterinary forms of
ivermectin and its stance that more studies are needed.
On May 4, a news story by Pfeiffer described the situation in the United States where hospitals were
refusing to treat patients with ivermectin but in multiple cases, family members of the patients taking
the hospitals to courts had resulted in the judges to order the hospitals to use ivermectin for those
individual patients [290]. As a reason for their initial refusal, a hospital had stated that ivermectin use
was not ethical because it was “not standard of care”, in addition to “not being an anti-viral medication”.
Another had stated that ivermectin was not consistent with their guidelines based on “recommendations
of professional societies, international government agencies and infectious disease expert opinions”. Asked
about a specific patient not having receiving the treatment, a doctor was quoted saying: “That’s one life.
I have a license to protect”.
On May 5, referring to March 2021 guideline by the US National Institutes of Health and the studies
by López-Medina et al. and Beltran-Gonzalez et al., the European Centre for Disease Prevention and
Control stated that ivermectin had not been shown to be effective against COVID-19 in clinical studies
so far as it had not shown any statistically significant difference in neither outpatients with mild disease
nor in hospitalized patients with a non-critical disease [291];[292];[141];[293].
On May 5, an in-silico study by Qureshi et al. explored the inhibition of importin-α1 by ivermectin with
several computational methods [294].
On May 5, a review by Abdelgawad et al. mentioned that there was no published data about ivermectin’s
efficacy or safety [295].
On May 6, the president of the Philippines had reportedly ordered a 1,200-patient, six-to-eight month
RCT on the efficacy of ivermectin on the early treatment of mild-to-moderate disease [296];[297];[298].
On May 6, FLCCC organized an expert panel discussion about standing up for human rights in COVID-
19 care [299]. Panel members were Barend Yus (South Africa), Michael Defensor (Philippines), Jackie
Stone (Zimbabwe), Ralph C. Lorigo (US) and Jean-Charles Teissedre (France). Kory said that “we are
working in a system which is not working for us . . . in which therapies are being restricted and deprived
from patients .. . ivermectin is probably the most absurd example of a system that is completely
dysfunctional and failing . . . we have to try to figure out how to correct that”.
Teissedre, a criminal law attorney working in Bon Sens [300] and also working for an alliance of 500
doctors in favor of ivermectin, had been working on obtaining a recommendation for ivermectin in France
since October 2020. The problem was that France and similar countries had “lost their power to decide”.
It was not a problem of supply or manufacturing but of prescribing and lack of a national guideline.
According to Teissedre, creating such a guideline appeared “blocked” by the health authorities which was
“difficult to understand”, yet in France judges didn’t want to legislate on matters that they thought of as
science and medicine. The legal action for a guideline had ended unsuccessfully but another legal action
for freedom of prescribing was ongoing. In addition, Teissedre was collecting evidence of scientific fraud
for a judge to investigate on. Teissedre said the doctors pay attention to national guidelines only; he
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added that “maybe they don’t read studies, maybe they can’t do that, maybe they don’t know [how to],
it’s a big problem” and that “if doctors would be a little bit brave, maybe the pandemic would be over
now with ivermectin”. He said there is not only the corruption by the industry but also “a psychological
problem of the doctors”.
Lorigo, an US lawyer, had been litigating against US hospitals in order for patients to obtain ivermectin in
hospital settings since January 2021. Utilizing FLCCC research materials he had successfully represented
a critical patient in Buffalo [159];[301], another critical patient in Rochester, and three additional
patients, against hospitals refusing to administer ivermectin [302]. Lorigo had not lost a single case,
yet hospitals had tried to fight back by saying it was not FDA approved. In the risk versus benefit
consideration by the judges, the hospital administration had ended up “out of bullets”, Lorigo said.
Yus from AfriForum, a civil rights organization with 280,000 members and a part of the community-
based Solidarity movement, described that access to ivermectin in South Africa had been the result of
the work of the Solidarity movement and recounted the timeline of ivermectin, started with people using
the veterinary form of ivermectin, with South African Health Products Regulatory Authority (SAHPRA)
deciding against ivermectin on December 22, Transvaal Agricultural Union of South Africa (TAU SA),
a commercial farmers union, requesting an investigation into ivermectin on December 29, SAHPRA
announcing on January 6 that it will consider access through Section 21, George Coetzee submitting
applications on January 15, Coetzee and AfriForum submitting an urgent court application on January
24, SAHPRA allowing controlled compassionate access on January 27, and the court ordering off-label
use of compounded ivermectin for COVID-19 on April 6. Due to lack of general access to human grade
ivermectin, the veterinary form was still widely used. Vaccines, even if available, would have been
unfeasible in rural areas without electricity. Yus had discussed the possibility of taking the WHO to
the International Criminal Court of Hague (ICC) but it had appeared that criminal cases needed to
be initiated locally in each country which would take years. Yus said that in order to overcome the
resistance on all levels, it was obligatory to organize people into large community-based organizations
because those could support major legal cases by crowdfunding. These communities could then balance
the interests of governments and large corporations.
Defensor, a Philippines congressman, said there had initially been a crackdown on ivermectin, and at
the moment of the discussion, prescribing it was prohibited, with the risk of losing the medical license.
Local manufacturers were not allowed to produce ivermectin, thus limiting supply. Remdesivir was used
nationwide but ivermectin was allowed in six undisclosed hospitals only. 533 doctors had supported access
to ivermectin. The president of the Philippines had noted there must have been a strong reason for the
doctors recommending ivermectin to put their reputations on line but the director of the Philippines’
FDA had dismissed the president’s observation, saying there was “not enough evidence to prove the
efficacy of ivermectin”. Defensor commented that “Big Pharma will continue to have a hold on our
health authorities and the leadership of our medical associations but the people cannot be stopped:
they listen, talk, read and watch, and spread the news about ivermectin. Our health authorities have
blood in their hands and we will fight them in the massacre of our people”. Defensor said doctors
in the Philippines were afraid of prescribing ivermectin. The situation had created a black market for
ivermectin. Defensor said cases against health authorities were being prepared on remdesivir-related
financial corruption.
Stone said that in addition to the mortality being 90% lower with ivermectin, the question had been
whether Zimbabwe would have had enough oxygen to be able to follow the WHO guideline on ivermectin.
It was not yet in the official national guideline but it was widely used off-label. Stone had been using
ivermectin “very publicly” since August 8, 2020, with other doctors joining. As one point, Stone had been
arrested (in her words, “ambushed”) “for dealing illegal drugs” (ivermectin) after having been reported
to medical licensing board by a group of doctors at the moment (Chinese) vaccines were arriving in
the country. Stone mentioned Chinese influence in Zimbabwe was huge. On the other hand, based on
experience of HIV-1, the authorities had understood that ivermectin was perfect for reducing mutations of
SARS-CoV-2, thus supporting efficacy of the vaccine. Stone said they had been using Thomas Borody’s
“triple therapy” [303] of ivermectin, zinc and doxycycline (a zinc ionophore) to avoid development of
ivermectin resistance; Stone said “the whole country knew exactly how to use it”. In Zimbabwe, a lot of
medications including ivermectin were given over-the-counter by pharmacists, overriding the opposition
of medical doctors who had refused to prescribe it. Stone said “the patients had driven this”. Stone
21
had been threatened by expulsion from a national research group if she had mentioned ivermectin there
again. Stone wanted to encourage physicians to stand up to the regulators; in her hearing, it had
become apparent that her well-prepared legal team had an opportunity to sue the regulator which, after
presentation of all the evidence by Stone’s team, had become unable to argue against ivermectin.
Kory said that “the fact that we are at war [against COVID-19] and [public health authorities] are putting
up these peacetime regulations: it’s not how war works. You don’t follow peacetime regulations at war
. . . we all keep talking about guidelines as if the guidelines are how we are going to win this .. . NIH
guidelines clearly state that they are not mandates . . . physicians don’t have to follow the guidelines
. . . they invite you in a shared decision making model to use your expertise, ability, your understanding
of the evidence . . . you still have autonomy . . . many physicians see them as mandates and are very
fearful of straying from them .. . it’s not what those documents are for . . . it’s time to recognize that
and take back some of that autonomy”. Kory concluded that “we are progressing .. . it’s time for civic,
social organizations around the world to step up and lead”.
On May 6, a preprint by Machanick described the conclusions of the FLCCC’s review in the American
Journal of Therapeutics [240];[236] as “a cruel hoax” [304].
On May 6, an article by Shahbaznejad et al. describing a multicenter double-blind randomized con-
trolled trial with 69 hospitalized patients administered a single dose of 0.2 mg/kg of ivermectin in Iran
(IRCT20111224008507N3) [305];[306]. Ivermectin reduced the frequency of lymphopenia, the duration
of dyspnea and persistent cough and the mean length of hospital stay. One critical patient in the treat-
ment group died within 24 hours of admission, causing the result to indicate increased mortality for
ivermectin.
On May 7, the Bill and Melinda Gates Foundation announced that in contrast to its previous policy on
defending COVID-19 vaccine related intellectual property of pharmaceutical companies, it had begun to
support a “narrow waiver for COVID-19 vaccines during the pandemic” [307].
On May 7, an editorial by Nardelli et al. presented a meta-analysis of seven ivermectin studies, indicating
lower mortality (2% vs 9%, OR 0.19, 95% CI 0.10-0.34, p<0.01, n=1,323) [308]. The authors noted that
lower mortality may have been due to resolution of Strongyloides hyperinfection. They said that in an
emergency situation, the use of a cheap medication without major side effects may be reasonable even if
strong verification of its efficacy is still lacking, and that results from the reported trials all point in the
same direction and cannot be overlooked.
On May 8, FLCCC announced a new protocol, I-MASS, for mass prophylaxis of populations [309]. For
prevention, 18 mg of ivermectin once a week, and 50 μg of vitamin D3and a multivitamin daily were
suggested. For outpatient treatment, 18 mg of ivermectin daily for five days, 6 mg of melatonin at night
for five days, and 80 mg of aspirin daily were suggested. Also, antiseptic mouth wash was suggested
three times daily. For post-exposure prevention, 18 mg of ivermectin on days 1 and 3 were suggested.
On May 10, a report stated that the rationale for a decision made in France by French medical authorities
to reject ivermectin was undocumented, breaking transparency laws and making it impossible to trace
who made the decision and through what kind of process [310];[311];[312];[313]. In response, 1,500
French physicians had signed a letter in protest. The organizer of the protest commented that ivermectin
was subject to “special treatment . . . the ASNM [French Agency for the Safety of Health Products],
WHO, EMA, NIH openly cheat, unscrupulously, with the blessing of so-called democratic governments”.
On May 10, an article by Faisal et al. about a RCT with 100 outpatients in Pakistan indicated 68.4%
lower risk of no recovery (12.0% vs 38.0%, RR 0.32, p=0.005) on days 6-8 (mid-recovery) [314].
On May 10, the state of Goa in India announced ivermectin will be distributed to all adults for pro-
phylaxis [315]. The dosing was said to be 12 mg for five days. Some experts commented that five days
was not enough and the medicine should instead be administered continuously until the pandemic was
brought under control.
On May 11, the state of Karnataka in India announced one million ivermectin tablets had been procured
and their supply was to begin on May 14 [315]. A further 2.5 million tablets were going to be procured
for state hospitals.
22
On May 11, the WHO’s chief scientist Soumya Swaminathan reiterated her and the WHO’s opposition
to India’s ivermectin plan, linking to a statement by Merck & Co/MSD claiming there is no evidence of
efficacy but considerable safety risks [316];[154]. The report also said doctors across India were being
pressured into giving drugs despite knowing that they are not effective against all forms of COVID-19
and irrespective of the patient’s medical history. The head of critical care of one hospital said that there
was no evidence and that only two very poor quality studies studies exhibiting a very strong bias existed.
On May 12, in the FLCCC weekly update, Kory again criticized the WHO saying they were hurting
the global public health but stated he saw “a sea change” happening, with more attention paid to the
failures of public health agencies, this criticism “supercharged” by the publication of the FLCCC’s review
in the American Journal of Therapeutics which, in about three weeks, had reached a position in the top
250 of over 17,700,000 articles ever tracked by Altmetric, and the first position among approximately
1,200 articles of similar age in all journals [317]. The review was available on PubMed Central (PMC)
with PMCID PMC8088823 but could not be found in the PubMed search portal and had no PMID
assigned [318].
On May 12, the FLCCC issued a statement “on the irregular actions of public health agencies and the
widespread disinformation campaign against ivermectin” [319], detailing flaws in WHO’s meta-analysis.
On May 12, a commentary by Bannister stated that an efficient medicine for COVID-19 would halt
the international vaccine rollout under Emergency Use Authorization (EUA), endangering the profits
of approximately USD 100 billion expected from vaccine sales in 2021 [320]. The author said that
the WHO had either made serious mistakes or deliberately undermined early treatment drugs in favor
of vaccinations, adding it was a huge windfall for vaccine manufacturers, with Pfizer set to receive
approximately USD 70 billion from vaccines over the next five years according to Morgan Stanley. He
said that an extension to the Trusted News Initiative (TNI) [321] in December 2020 had led to censorship
of early treatments, adding that “almost every media house around the world has contributed to the
marginalization of ivermectin”.
On May 12, a news report stated that the state of Uttarakhand in India will mass distribute ivermectin
as prophylaxis [315]. The dosing for people over 15 was said to be 12 mg twice daily for three days, a
total of 72 mg. For children between 10 and 15 years the dosing was half of that. For children between
2 and 10 years ivermectin was to be administered only by prescription, and not administered at all to
children below 2 years, pregnant women and people suffering from liver diseases.
On May 13, a news report stated that the state of Odisha in India was to buy 720,000 ivermectin
tablets for patients in isolation [322]. Despite the WHO guidance against ivermectin the state health
department strongly recommended its use. A prophylaxis trial carried out at the All India Institutes
of Medical Sciences (AIIMS) in Odisha in mid-2020 had indicated a 73% reduction of SARS-CoV-2
infection among healthcare workers for the following month after administration of 0.3 mg/kg ivermectin
on days 1 and 4 (preprint published on November 3, 2020 [323];[324], peer-reviewed article published on
February 16, 2021 [325]). A local professor commented that “there is no time to wait for a clinical trial
during the ongoing emergency situation . . . ivermectin is an immune-regulatory and anti-parasite drug.
It has few side effects. In the given circumstances, it should continue to be used as certain studies show
promising results”. The suggested dosing was 12 mg daily for three days.
On May 13, an article by Mahmud et al. described a randomized trial with mild-to-moderate disease
treated with a combination of ivermectin and doxycycline with 183 patients in the treatment group and
180 controls (NCT04523831), the results of which were initially published on October 9, 2020 [326];[327].
According to the CovidAnalysis group, the trial indicated 96% lower risk of no recovery on day 12 (23.0%
vs 37.2%, RR 0.04, p<0.001), 57% lower risk of disease progression (8.7% vs 17.8%, RR 0.43, p<0.001)
and 39.0% lower risk of no virological cure (7.7% vs 20.0%, RR 0.61, p<0.002) [328].
On May 13, ivermectin was officially included in the ACTIV-6 trial with 15,000 patients
(NCT04885530) [329]. The estimated start date was May 2021, the estimated primary completion date
December 2022, and the estimated study completion date March 2023.
On May 13, Campbell discussed the plan of the state of Goa in India to distribute prophylactic ivermectin
for all adults [330].
23
On May 13, an interview of Didier Raoult discussed vaccines and corruption [331];[332]. Raoult noted
that among the vaccinated there were fewer hospitalizations but not fewer deaths, adding that because
the proportion of asymptomatic carriers remained extremely high the current data did not confirm that
vaccines significantly reduced circulation of SARS-CoV-2. Corruption, he said, was as old as the world,
and all of the current producers of vaccines had been convicted of corruption: Gilead had been fined USD
97 million, Pfizer USD 60 million, AstraZeneca USD 5.5 million, and also GSK. He described scientific
publishing as a profitable business with profits of 35% per year, saying that a significant part of the
revenue of premium journals comes directly from pharmaceutical industry, and as soon as a scientific
journal reached a large enough audience it became a target of science akin to marketing. Raoult saw
it necessary to recreate the seal between public interest activities and the industry, and said he did not
think that participating in industry-led trials contributed to knowledge, adding “it is not research to
include patients in a trial carried out by the pharmaceutical industry, whose analysis is made by the
pharmaceutical industry, whose methodology was decided by the pharmaceutical industry and even the
publication of which was written by the pharmaceutical industry and then offered to and accepted in one
the biggest journals . . . we must return to science that contributes to knowledge . . . it is also necessary
that ethics committees, rather than looking at the methodology, should ask themselves questions about
the ethics of clinical trials”.
On May 13, a news report from Hungary described that ivermectin tests in Hungarian hospitals had been
going well and in a few months ivermectin would likely be prescribed off-label for COVID-19 outpatients
in Hungary. The article said this would be a “major breakthrough”, as the pharmaceutical institute had
so far explicitly banned anyone from using the drug for COVID-19, with the government even prosecuting
a woman who had ordered a dose from South Asia. A local pharmaceutical company was beginning to
produce generic ivermectin, and a 70-patient phase II clinical trial managed by the University of Debrecen
was ongoing [333].
On May 13, an article by Konne et al. reviewed ivermectin and concluded that it could be a remarkable
medical breakthrough for the lasting treatment of COVID-19 [334].
On May 14, Hegazy et al., a group that in 2020 had carried out an ivermectin RCT in Egypt [335];[261],
published a review of ivermectin and suggested that ivermectin could be used for mass chemoprophylaxis
of populations with minimal risk [336].
On May 16, a commentary titled “Who’s advising WHO on the pandemic?” by a former president of
Jamaica Medical Doctors Association criticized WHO for the hypocrisy of claiming to be attempting to
save lives and ending the pandemic while at the same time recommending against the use of prophylactic
and therapeutic options [337].
On May 17, a news report described a strong disagreement on whether the state of Goa in India should
distribute ivermectin against the advice of the WHO [338].
On May 17, a preprint by Bryant et al. provided an updated version of the BIRD group’s ivermectin meta-
analysis [339]. Twenty-four RCTs involving 3,406 participants met review inclusion. Meta-analysis of 15
trials found ivermectin reduced risk of death by 62% (95% CI 27%-81%) compared with no ivermectin
(RR 0.38, 95% CI 0.19-0.73, n=2438, I2=49%, moderate-certainty evidence). Low-certainty evidence
found ivermectin prophylaxis reduced infections by an average 86% (95% CI 79%-91%). Effect estimates
for ‘improvement’ and ‘deterioration’ clearly favored ivermectin use. Severe adverse events were rare
among treatment trials and evidence of no difference was assessed as low certainty. In conclusion,
moderate-certainty evidence found large reduction in mortality to be possible.
On May 17, a book chapter by Kapoor et al. reviewing pharmacotherapy for COVID-19 mentioned
ivermectin trials in India and Bangladesh [340].
On May 18, a Twitter post by WHO African Region, labeled with “Fact-check” and “ViralFactsAfrica”
tags, stated that “ivermectin does not prevent COVID19 and is not an effective treatment for the virus.
The medication is used to treat parasitic worms .. . Unproven claims about miracle cures for COVID-19
have been around for almost as long as the pandemic. One of these is ivermectin . . . it has recently
resurfaced in Kenya. But there’s no evidence to support the use of ivermectin to prevent or treat COVID-
19 . . . follow trusted sources like the WHO, Africa CDC and Unicef for the latest COVID-19 info. If
you catch the virus, see a health care provider to get approved COVID-19 treatment” [341]. Of tens
24
of tweets posted by WHO African Region in the latter half of May, a majority concerned vaccines and
the COVAX program. WHO African Region also retweeted posts by Gavi The Vaccine Alliance, and by
Tedros Adhanom Ghebreyesus which celebrated WHO’s partnership with COVAX.
On May 18, the Times (UK) wrote that Bill Gates had sought the help of the convicted sex criminal
Jeffrey Epstein to get connected to influential people in order to improve chances of winning the Nobel
Peace Prize [342];[343]. Another report wrote that a former employee had said the prize was “what Bill
wants more than anything else in the world” [344].
On May 19, an opinion article by Mookim in Wired magazine wrote about Bill Gates’ “vaccine colo-
nialism” and “intellectual property stubbornness”, saying “the question is not whether people in rich,
Western countries will be prioritized over people in the Global South. Rather, it’s whether large Western
corporations will benefit to the detriment of people everywhere” [345]. Mookim noted that the Biden
administration had recently come out in support of waiving intellectual property rights to coronavirus
vaccines, after which the Bill and Melinda Gates Foundation also had reversed course and endorsed
the patent waiver [307] but Bill Gates himself had not. The article described that a WHO initiative,
a patent-free technology sharing pool C-TAP announced in early 2020 would have removed intellectual
property barriers for accessing COVID-19 treatments and vaccines but Gates, “maintaining his steadfast
commitment to intellectual property rights”, had blocked the plan in order for companies to retain ex-
clusive rights through Gates-initiated COVAX program, regardless of the vaccines and medicines having
been developed largely with public funding. Mookim described that COVAX “enshrines monopoly patent
rights and relies on the charitable whims of rich countries and pharmaceutical giants .. . should we be
surprised that a monopolist-turned-philanthropist maintains his commitment to monopoly patent rights
as a philanthropist too?” Mookim recounted Gates’ anticompetitive practices at Microsoft, calling him
a “ruthless monopolist”, adding that he “chose to launder his reputation by tried and true philanthropic
giving. But as he pivoted to global health, his faith in exclusive IP rights remained unchanged”. Mookim
also recounted Gates’ opposition to generic AIDS medicines for Africa, his two-decade advocation of
anticompetitive public health policies, and the Gates Foundation’s continuing acquisitions of substantial
intellectual property, also throughout the pandemic. In 2020, Gates was said to have leveraged his USD
750 million donation to Oxford University to convince it to not open-license its COVID-19 vaccine. As
a result, the rights to the vaccine were sold to AstraZeneca, “with no guarantee of low prices and an
extraordinary opportunity for profit”.
On May 19, in a FLCCC weekly update, Kory and entrepreneur Steve Kirsch, the founder of an COVID-
19 Early Treatment Fund (CETF) [346], discussed early treatments with ivermectin and fluvoxam-
ine [347].
On May 19, an interview of an early outpatient treatments pioneer Peter McCullough, who had already
published 40 peer-reviewed articles on COVID-19, described the policy response to the pandemic as
“profoundly disturbing” [348]. McCullough described the federal agencies CDC, FDA and NIH as “enor-
mously inept in terms of perceiving what the problem was and in applying any type of judgment or
direction to doctors . . . what happened was that the doctors were so terribly frightened that they said,
‘we are not going to do anything unless we get intellectual support from our associations, from our federal
agencies, from our medical societies’. And it was just the opposite of what medicine had always been:
early innovation by doctors, empiric treatment, small studies, randomized trials, and then sponsored
randomized trials, in that order, and then after large trials, guideline bodies looking at those trials, then
federal agencies . . . it always started out with early empiricism, then getting to guidelines, years later”.
He added that “it was a dangerous assumption to assume there is nothing one can do to a fatal infection”,
that due to poor precautionary measures “every hospitalization in America was a superspreader event”,
and that “this assumption that there is nothing we can do when giving someone a fatal diagnosis with no
instructions led to a massive amplification of cases .. . remarkably, not a single academic or community
medical center today treats COVID-19 patients as outpatients with the goal of reducing hospitalizations
and deaths”.
McCullough described US pandemic response as very weak, saying that “to this day, we still have not
had a doctor in any position of authority in the United States who has actually ever seen a patient with
COVID-19 and treated them .. . it is extraordinary .. . there was an enormous pressure to suppress
early treatments .. . the false paper published in the Lancet was extraordinary . . . we started to have
25
an array of incredibly flawed papers publishing exaggerated cardiac effects of hydroxychloroquine .. . as
the data came out on ivermectin, it became the next drug”.
McCullough said that “when the next patient called asking: ‘Can you help me?’ each doctor had a binary
choice, either: ’No, nothing works, there’s nothing I can do, just wait until you get hospitalized”, or the
answer could be: ‘You know what, let me try’. And what we found was that this binary choice was the
biopsy of who really had courage and excellent clinical judgment. Doctors who were not confident in
their clinical judgment quickly said there’s nothing they can do and they got into that groupthink. And
that could have been over 90% of doctors who had a lack of clinical judgment and a lack of courage.
What I found was that those two things are rare . . . we have 600,000 dead Americans, the vast majority
of whom didn’t get an ounce of treatment .. . that will go down in history as a shame for our country
. . . there are many ways to treat this illness .. . what I have learnt is that if doctors do almost anything
they can reduce hospitalizations and deaths . . . the only [reason for the disaster] is that doctors failed
to act".
On dismissal of off-label treatments, he said that because of the tremendous fear that settled in, state-
ments from the FDA, NIH and CDC started to take more weight than they ever would have in the
past, pharmacies did not dispense prescriptions, and doctors started to get warning letters from medical
boards. McCullough said that “we were getting official messages that basically said: don’t take care of
COVID-19 .. . these are codified in policies and emails by major medical organizations . .. we have never
seen this [before for any other disease] . . . there is a term that applies to what’s going on, wrongdoing
by those in positions of authority: malfeasance”. He added that at the same time there were Association
of American Physicians and Surgeons (AAPS), FLCCC and BIRD saying “this is wrong; treat patients”.
He commented that “the reason why you are talking to me today, instead of some FDA official, is because
you are getting the sense of reality that this virus is treatable .. . we made everything far worse by not
treating it, keeping patients in fear and isolation .. . we have done multiple things that have promoted
hospitalization and excess mortality”.
On May 20, an open letter from researchers, medical doctors and NGO representatives to the Ministry
of Health of Malaysia presented current research evidence on ivermectin and criticized Malaysia’s lack
of adoption of it [349].
On May 20, author and journalist Michael Capuzzo called upon journalists to cover ivermectin calling it
“a historic opportunity . . . for the first time in the long journey from Gutenberg to Google, journalists
may be the ones to save the world” [350]. His report covered legal battles in the US about prescribing
ivermectin to a couple of hospitalized patients, as well a very extensive coverage of the history of the
FLCCC [351]. Capuzzo also claimed that unreported by the press, president Trump had been adminis-
tered ivermectin at Walter Reed hospital. The report also covered recent experiences in India, quoting
an Indian surgeon and hospital owner describing that ivermectin saved India in 2020 after it got official
permission in Uttar Pradesh in August followed by many other states but after political changes in Jan-
uary 2021 it started getting “bad propaganda by big pharma and big scientists”, leading many doctors to
stop using it. That, in turn, led to collapse of prevention and home treatment, seeding the subsequent
crisis of overloaded hospitals and many needless deaths in the first half of 2021. The surgeon stated
that “we beg health agencies and mainstream media in other countries not to give bad propaganda of
ivermectin .. . it is saving India and Africa”.
On May 21, a news report stated that the University of Minnesota was adding ivermectin to an on-
going outpatient trial with hypoxia, emergency department utilization and post-COVID-19 syndrome
prevalence as primary endpoints (NCT04510194) [352]. The trial, with an estimated enrollment of 1,160
patients, included arms for metformin, fluvoxamine, ivermectin, metformin and fluvoxamine, metformin
and ivermectin, and placebo. Estimated primary completion date was October 2021 and estimated study
completion date December 2021.
On May 23, the First International Ivermectin Summit was organized online by the BIRD group [353];
[354]. The speakers included Martin Gill (South Africa), Jackie Stone (Zimbabwe), Sabine Hazan (US),
David Scheim (US), Jennifer Hibberd (Canada), Lucy Kerr (Brazil), Kylie Wagstaff (Australia), Tess
Lawrie (UK) and Thomas Borody (Australia).
26
Gill said the front line doctors are left to what they have, and have to repurpose drugs and come up with
protocols that will work. As soon they find one that is working they do a small trial because they need to
get information out so that it will be further researched and used around the world. Gill said these small
studies are not meant for decision makers but for researchers to have a guideline of what to research. He
said the situation with ivermectin was unique due to data on ivermectin being way beyond the point of
needing further data since no further data was unlikely to change the conclusion that ivermectin worked
so well that it could change the course of the pandemic.
Stone presented her experiences with severe cases and described that early treatment with high doses
with titration to effect and with a combination therapy utilizing zinc and doxycycline had improved
results in comparison to ivermectin only. She said combination therapy reduced oxygen requirements,
an important factor since they often did not have access to oxygen. She said their “hospital at home”
approach had resulted in a mortality rate approximately 90% lower than in state hospitals, adding
that the mortality rate in moderate to severe inpatients should be less than 1%. She described a
few patient cases, stressing the importance of early anticoagulation, aggressive diabetes control, and
home nursing on oxygen, adding that the response was a dose dependent. She also said D-dimer was
a marker of clot breakdown and an increase in D-dimer indicated recovery instead of deterioration.
They had developed a treatment protocol (0.3-0.6 mg/kg ivermectin, ceftriaxone, dexamethasone, zinc,
doxycycline, prednisolone, enoxaparin) that had been widely distributed in Zimbabwe so that nurses had
learnt to treat patients following the protocol. A January 26, 2021 statement from Zimbabwe Ministry
of Health had stated it was important to not deny patients effective treatment regimes. Stone said it
was “perhaps time we stood away from what the Northern hemisphere is doing because to be perfectly
honest it doesn’t really look like it’s working”.
Hazan said her team had carried out one of the first ivermectin trials. Hazan had used “Ziverdox”
protocol consisting of 12 mg of ivermectin on days 1, 4 and 8, 100 mg doxycycline BID, 50 mg of zinc,
3000 IU of vitamin D, and 3,000 mg of vitamin C. Some of her patient cases had been described in the
local press [355]. She stressed the importance of “making the patients feel that you are trying to save
them” and the importance of combination therapy.
Scheim presented an analysis of ivermectin distribution in Peru, describing that introduction of iver-
mectin had first caused a 14-fold reduction in excess deaths of people over 60 years old, and subsequent
restrictions introduced by a new president had caused a 13-fold increase, respectively. Community mo-
bility, household densities and seropositivity rates were considered as confounding factors. One state
without ivermectin distribution differed sharply from states with distribution (74% vs 25% reductions in
excess deaths, p<0.02).
Hibberd presented world data on ivermectin collected by her and Juan Jose Chamie. According to her,
India’s second wave started from the city of Mumbai in the state of Maharastra, and from the state of
Punjab (originating from Pakistan). Migrant workers fleeing from Mumbai spread the virus especially
to the city of Lucknow in the state of Uttar Pradesh. New viral variants were detected in regions where
Astra Zeneca vaccinations had been implemented, a pattern also noted for other countries including
the UK, South Africa and Brazil. The media represented remdesivir as very effective and ivermectin as
unproven and outdated. On April 21, 2021, the national guideline was updated to include ivermectin.
Daily death rates stabilized and case counts dropped in Maharastra and Uttar Pradesh. In Tamil Nadu,
a state without ivermectin distribution, deaths and case counts had continued increasing. In Mexico,
according to Hibberd, the pandemic was under control, with ivermectin being the main factor in enabling
that.
Kerr reviewed the pathophysiology of COVID-19 and mechanisms of action of ivermectin. Kerr was the
leader of a group “Doctors for Life” with 12,000 members in Brazil. The group was teaching principles of
early treatment to clinicians but also in for example factories with lots of workers. The group’s protocol
was similar to the FLCCC’s, with minor differences in dosing. Kerr also stated there had been no issues
with using ivermectin for pregnant women and for children over 15 kg.
Wagstaff, one of the authors of the Australian in vitro study published in April 2020 [7], explained
that due to for example lack of adaptive immune responses in the cell model, the in vitro study was
irrelevant for considerations of dosing in humans, rendering arguments against ivermectin based on the
in vitro IC50 value groundless. She explained that since ivermectin was a host acting agent it was
27
working in conjunction with immune system. Therefore, 1:1 ratio of drug to virus was unlikely to be
required. Ivermectin also accumulated in the lungs and other tissues. She said they were looking whether
ivermectin analogues possessed similar effects.
Lawrie said researchers had a fundamental moral obligation to share preliminary results through pre-
publication mechanisms. Journals were not to hinder this sharing of data, and WHO’s norms for public
health emergencies also encouraged sharing. According to Lawrie, in the case of ivermectin there had
been no support to low-and-middle income countries and their clinician-researchers, no editorial support
from journals, nor financial support from public health authorities. Instead, the response had been char-
acterized by a systematic denigration of the quality of studies, systematic hindarance to publication, and
systematic disinformation and censorship from public health authorities, pharmaceutical companies and
the “big tech”. In the UK, National Institute for Health and Care Excellence (NICE) had been silent
on ivermectin although according to Lawrie evidence for it had existed at every level of the evidence
pyramid. In contrast, the use of remdesivir and some other pharmaceuticals had been authorized in
the UK on very little evidence. She said the latest meta-analysis by Karale et al. [285] supported the
conclusions of the BIRD group. She also mentioned the Catracho protocol of Honduras [70] and the
experience of Mexico [284]. International doctors’ groups in favor of ivermectin included FLCCC, BIRD,
Doctors for Life (Brazil), Canadian Covid Care Alliance, UK Medical Freedom Alliance, Association of
American Physicians and Surgeons (AAPS), Ippocrate.org, United Health Alliance, and HART. Accord-
ing to Lawrie, major opponents to ivermectin were the ACT-Accelerator with USD 38.1 billion funding,
and the Trusted News Initiative (TNI).
On May 24, a Finnish company Therapeutica Borealis got a US patent for a nasal spray containing
ivermectin, hydroxychloroquine and aprotinin, a protease inhibitor [356]. The company said active
ingredients were used in a new, targeted manner on the upper respiratory mucous membrane, so that
the concentrations of the active ingredients throughout the body remained very low but were sufficient
locally to prevent the passage and replication of the virus, making the drug safer and more effective.
On May 24, FLCCC announced that they had been locked out of their Twitter account for “violation of
Twitter rules” [357].
On May 24, a Belgian virologist with experience in vaccine research and development in several pharma-
ceutical companies, the Bill and Melinda Gates Foundation, Gavi The Vaccine Alliance and the WHO,
Geert Vanden Bossche, presenting a review of unsolved issues in COVID-19 vaccine related immunology,
proposed early multidrug treatment (with e.g. ivermectin as one of the components of an early treatment
kit) as a way out of the “mismanaged pandemic” [358];[359]. Bossche said it was “difficult to imagine
how [’updating’ vaccines] could solve the problem of immune escape SARS-CoV-2 variants”. Bossche
referred to a steadily growing community of world-class scientists and experts calling for an immediate
halt to the mass vaccination campaigns as the only method. Instead, early treatment proven highly
efficient, practical and cost-effective should have been made widely available. He said quick ‘updates’
of the current Covid-19 vaccines would most likely fail to solve the pandemic because they were still
based on an immunological concept and mechanism that didn’t address the risk of evolutionary immune
escape. He predicted SARS-CoV-2 to become resistant to current vaccines and asked the vaccine com-
munity to develop vaccines with a different mechanism of action. Regardless, he predicted that it would
be necessary to rely on a short but large scale course of antiviral drug treatment using a compound that
can be made available in high quantities at low cost, adding that ivermectin would seemingly qualify. He
concluded that “a well-coordinated and targeted drug treatment program could be a game-changer and
turn the tide of this pandemic in that it could drastically reduce the chain of viral transmission, not at
least in vaccinees. Whether sensibly targeted virucidal chemoprophylaxis will provide populations with
sustained protection from COVID-19 in the post-pandemic era and hence, serve as a full-fledged substi-
tute for herd immunity is likely but unproven. Virucidal chemoprophylaxis seems, however, a promising
option, the effectiveness of which could rapidly be explored at low cost and without raising the type of
safety concerns that are associated with the ongoing mass vaccination campaigns”.
On May 24, entrepreneur Steve Kirsch, who had earlier founded a COVID-19 Early Treatment Fund
(CETF) which had funded fluvoxamine trials [346], offered an USD 1 million prize for any professor,
licensed physician, medical journal editor, NIH or WHO employee, mainstream media reporter, elected
official, public health official, or YouTube or Facebook censor who would provide a convincing argument
28
to a panel of Kirsch-selected judges that the current NIH or WHO recommendations on fluvoxamine or
ivermectin were more likely to fit the evidence than recommendations to support the use of both drugs,
or who could show that the recommendations were more likely to save more lives than recommending for
these drugs [360]. The prize was offered separately for each of the two medicines, making a total of USD
2 million. Kirsch said the evidence for both drugs had been in plain sight for over 7 months, yet Anthony
Fauci and Francis Collins (NIH) had remained silent. “If a computer entrepreneur from Silicon Valley
can figure all this out seven months ago that it’s virtually impossible for these two drugs not to work,
why can’t the NIH leadership?” Kirsch asked, adding that “why, when David Seftel confirmed the 100%
success rate in the original fluvoxamine RCT published in JAMA [on November 12, 2020 [361];[362]]
with a real-world study also with 100% effect size [on February 1, 2021 [363]], did they just ignore it like
it never happened? Why didn’t they send a team to investigate if there were any biases or confounders?
Instead, they just sat back and did nothing when the news came out. There was no investigation.
There wasn’t even a phone call or email to the investigator. Even after 60 Minutes did a story on this
miracle at the racetrack [on CBS News on March 8, 2021 [364]], they still did nothing to investigate.
They could have saved hundreds of thousands of lives if they had acted earlier on the evidence that was
hiding in plain sight for at least the past 7 months”. Kirsch also mentioned that in the beginning of
December 2020, the blog platform Medium had, “in response to my efforts to bring this lifesaving advice
to the world’s attention, suspended my account, removed all the content I had written over the past 7
years, and banned me for life”. Kirsch had asked if Medium had any factual information supporting their
contention that he was incorrect, to which Medium had responded only that they believed my comments
constituted elevated risk because I was making “health claims or advice which, if acted on, are likely to
have detrimental health effects on persons or public safety”.
On May 24, ivermectin tablets were being sold over-the-counter without prescription nationwide in the
Philippines, with the Philippines government funding a clinical trial on the president’s order, in parallel
with ivermectin distribution to the public [365].
On May 24, in the state of Goa, India, ivermectin tablets promised to health centers and villages, with
a value of approximately USD 3,000,000, had reportedly gone missing [366];[367].
On May 25, a preprint of a meta-analysis by Roman et al. describing a meta-analysis of ten ivermectin
trials (n=1,173) utilizing Cochrane tools and GRADE methodology concluded that in comparison to
standard of care or placebo, ivermectin did not reduce all-cause mortality, length of stay or viral clear-
ance in RCTs in COVID-19 patients with mostly mild disease, that ivermectin did not have effect on
adverse effects or severe adverse effects, and that ivermectin was not a viable option to treat COVID-19
patients [368].
On May 25, data analyst Alvaro Olavarría, the founder of the Tratamiento Temprano (“early treatment”)
website [369], noted on Twitter that the meta-analysis by Roman et al. had swapped the mortality results
of ivermectin and control arms of one of the included RCTs (Niaee et al. [123], n=180) [370]. According
to commentators, if the error had been be corrected, the meta-analysis would have indicated a mortality
reduction of 66% (p=0.031) [371]. Olavarría claimed the case was “an obvious disinformation campaign
by colleagues” [370].
On May 25, the BMJ published an article by Clarke discussing fact-checking health and science on
Facebook, saying that Facebook had removed 16 million pieces of its content and added warnings to
around 167 million, and that YouTube had removed more than 850,000 videos related to “dangerous
or misleading COVID-19 medical information” [372]. The article also mentioned that Facebook and
YouTube were relying on third party fact checkers funded by parties such as the Charles Koch Institute
related to the billionaire Charles Koch [373];[374];[372]. Clarke concluded that the approach taken by
social media platforms could ultimately undermine trust in public health, and that in the US, trust in
the government and media was already falling.
On May 25, the video of the First International Ivermectin Summit by the BIRD group was removed by
YouTube for violating YouTube’s Community Guidelines [375].
On May 25, the Indian Bar Association, a lawyers’ association in India, sent a legal notice to Soumya
Swaminathan, the chief scientist of the WHO [376];[377]. The 51-page document accused Swaminathan
of running a disinformation campaign against ivermectin by deliberate suppression of its effectiveness
29
despite the existence of large amounts of clinical data, issuing statements in social media and mainstream
media to turn the public against the use of ivermectin and to attack the credibility of the Indian Council
for Medical Research (ICMR) and All India Institute of Medical Sciences in Delhi (AIIMS) which had
included ivermectin in the national guidelines, and abusing her position by repeatedly issuing statements
with an intention to mislead and create confusion. The notice also stated that WHO’s reports were
increasingly seen as biased and lacking in quality, authenticity and rational approach. Copies of the
document were sent to the president and the prime minister, governors of all states, and to medical
associations and administrative offices.
On May 25, an opinion in a Cyprus newspaper asked about lack of early treatment for COVID-19, espe-
cially ivermectin treatment, noting that “to a layman . . . the behavior of governments and public-health
authorities seems bizarrely wrong, just from a common-sense standpoint . . . I try to gauge who’s telling
the truth by judging their conduct – and so far, the early-treatment proponents are more convincing”
[378].
On May 25, University of Minnesota Medical School announced its multi-site clinical trial had received
USD 1 million from the Rainwater Charitable Foundation and USD 500,000 from Fast Grants to add
ivermectin to their first randomized clinical trial for COVID-19 in the world to include pregnant wo-
men [379];[380]. Fast Grants were supported by Arnold Ventures, The Audacious Project, The Chan
Zuckerberg Initiative, John Collison, Patrick Collison, Crankstart, Jack Dorsey, Kim and Scott Farquhar,
Paul Graham, Reid Hoffman, Fiona McKean and Tobias Lütke, Yuri and Julia Milner, Elon Musk, Chris
and Crystal Sacca, Schmidt Futures, Amazon Web Services and others.
On May 26, an industry report enumerated COVID-19 therapeutics in development in Germany, Austria
and Switzerland [381].
On May 26, the preprint of a meta-analysis by Roman et al. was updated to correct an error, yet its
conclusions about mortality remained unchanged (“ivermectin did not reduce all-cause mortality”, RR
0.37, 95% CI 0.12-1.13) [382]. Commentators on medRxiv and the CovidAnalysis group pointed out
additional uncorrected errors in numbers of patients, numbers of events, duration of hospital stay, and
events being represented on the wrong side, noting that all errors were in the direction of showing lower
than actual efficacy of ivermectin, and adding that the included studies were “cherry-picked” [383].
On May 26, an article by Samaha et al. about a RCT in Lebanon indicated that a single dose of ivermectin
lowered the risk of fever on day 3 by 90.9% (2.0% vs 22.0%, RR 0.09, p=0.004 (ChiCTR2000033627) [384];
[385].
On May 26, a patent attorney and a former director of intellectual property at Gilead Sciences Inc.,
Brian Remy, commenting on an article asking whether “ivermectin is the new penicillin” [386], said that
“it’s simple, use what works and is the most effective – period” [387]. Remy added that “ivermectin used
in combination with other therapeutics is a no-brainer and should be standard of care for COVID-19
. . . other viral infections are treated most effectively with combinations (HIV, HCV, etc.). Thus, there
is no reason why ivermectin (with a superb safety profile) should not be combined with other generic or
patented therapeutics. For example, as a recommended treatment add-on or formulation, unless there are
adverse drug interactions, or legitimate IP/patent business reasons – which would be rare for such an old
generic drug. The best expert physicians know this and are already doing this (not only with antivirals,
but with anti-inflammatories and anticoagulants, with great success, efficacy and safety)”. Remy referred
to a December 2020 article by McCullough et al. on multifaceted highly targeted sequential multidrug
treatment of early ambulatory high-risk SARS-CoV-2 infection [388], saying “everyone should be following
their lead and approach .. . not only would this be good for business and help avoid the criticism, bad PR,
and potential civil/criminal liability for censorship, scientific misconduct, etc. etc. for misrepresenting
ivermectin and other generics but most importantly it would save countless lives and end this pandemic
for good”. A few days earlier, Remy had commented that “ivermectin crushes Delhi cases and provides
more evidence for a potential win/win solution for patients and companies with non-generic patented
therapeutics (criticized for cost, efficacy, etc.), to work on updating their clinical trials/labels to include
ivermectin (if possible). For example, as a recommended treatment regimen in the ‘Indications and Usage’
and ‘Dosage and Administration’ sections, increasing efficacy by additive (possibly synergistic) effects in
a combination approach, maybe even a combination formulation product. It would look great from a PR
perspective as well. Just some thoughts. I love it when everybody wins!” [389].
30
On May 28, a news report in Forbes India said that drugs such as ivermectin continued to be on India’s
health ministry’s treatment protocol despite evidence not inspiring confidence, and that the regulator
was approving medicines without following due scientific process, experts had said [390]. According to a
director of critical care at a major hospital and a member of state of Maharashtra’s COVID-19 task force,
only corticosteroids and oxygen were backed by evidence. A pulmonologist said hydroxychloroquine and
ivermectin needed to be taken out of the treatment protocol and called for an all-India committee with
government, private players and central institutes to finalize treatment protocols. He saw promise in two
new antibody cocktails that had recently received emergency use authorizations. These products were
said to be priced at approximately USD 900.
On May 29, an Austrian weekly magazine wrote about ivermectin, describing it as having a high efficacy,
yet being opposed by WHO and the “mainstream” [391].
On May 29, a news report from Spain interviewed José Muñoz who was initiating an 800-patient clinical
trial on ivermectin [392]. Muñoz said they had been trying various drugs for 1.5 years and so far the success
had not been equivalent to that of vaccines and that they now wanted to trial high-dose ivermectin.
On May 30, in a blog post citing FLCCC materials, bishop Thomas Schirrmacher, the president of the
International Council of the International Society for Human Rights (ISHR) and the secretary general of
the World Evangelical Alliance (WEA) which networks churches with 600 million conservative Protestant
Christians, stated that ivermectin treatments are safe and effective and could save many lives and speed
economic recovery [393].
On May 31, the FLCCC announced it had regained access to its Twitter account but Cision PRWeb and
PR NewsWire had announced they would no longer distribute FLCCC’s press releases. YouTube had
also removed two more videos by FLCCC.
On May 31, version 85 of the CovidAnalysis group’s meta-analysis indicated that all 17 RCTs for prophy-
laxis and early treatment reported positive effects, with an estimated 83% improvement for prophylaxis
(RR 0.17, 95% CI 0.05-0.61, n=1,974) and 73% improvement for early treatment (RR 0.27, 95% CI
0.18-0.41, n=1,826) [394]. For late treatment, eleven RCTs indicated 42% improvement (RR 0.58, 95%
CI 0.38-0.90, n=1,197). Together, all 28 RCTs indicated 66% improvement (RR 0.34, 95% CI 0.24-0.50,
p<0.0001, n=4,997). For mortality, three RCTs about early treatment indicated 83% improvement (RR
0.17, 95% CI 0.03-0.96, n=876), six RCTs about late treatment indicated 62% improvement (RR 0.38,
95% CI 0.17-0.85, n=922). Together, the nine mortality trials indicated 66% improvement (RR 0.34, 95%
CI 0.17-0.67, n=1,798). Together, all of the 56 RCTs and observational studies indicated 72% improve-
ment (RR 0.28, 95% CI 0.21-0.36, p=0.00000000000041, n=18,447).
June 2021
On June 2, the FLCCC updated its I-MASS protocol intended for mass prophylaxis [395];[396]. Iver-
mectin dose for outpatient treatment (daily for five days) was raised from 18 mg to 24 mg.
On June 2, a RCT with 164 patients by Abd-Elsalam et al. failed to produce statistically significant
results [397].
On June 3, Wang et al. (a group including Andrew Hill) reviewed production costs of potential repurposed
drugs for COVID-19, including dexamethasone, ivermectin, dutasteride, budesonide and colchicine [398].
They indicated that repurposed therapies could be generically manufactured at very low per-course costs,
for example USD 0.12 for ivermectin. They concluded that the analyzed drugs were widely available and
affordable, and that successful management of COVID-19 required equitable access to treatment for all
populations, not just those able to pay high prices.
On June 6, a systematic review and meta-analysis of 19 RCTs with 2,768 patients by Hariyanto et al.
indicated that ivermectin was associated with 69% reduction in mortality (RR 0.31, 95% CI 0.15-0.62,
p=0.001), 57% reduction in severity of COVID-19 (RR 0.43, 95% CI 0.23-0.81, p=0.008), higher negative
test result rate (RR 1.23, 95% CI 1.01-1.51, p=0.04), shorter time to negative test result (mean difference
-3.29, 95% CI -5.69 to -0.89, p=0.007), higher symptoms alleviations rate (RR 1.23, 95% CI 1.03-1.46,
p=0.02), shorter time to symptoms alleviations (mean difference -0.68, 95% CI -1.07 to -0.29], p = 0.0007)
31
and shorter time to hospital discharge (mean difference -2.66, 95% CI -4.49 to -0.82], p=0.004) [399]. The
authors concluded that more randomized clinical trial studies were still needed to confirm the results.
On June 7, in a blog post in the Science Magazine, Lowe wrote that while it was not important to know
the mechanism of action, the trials he had reviewed had used doses far too low in comparison to the
required level in vitro [7], the WHO had done a solid job in evaluating the literature [83], the JAMA
study [141] had found no benefit, the issue reminded him of the hydroxychloroquine situation, and he
was “not having it with people going the conspiracy theory route” [400].
On June 7, the Union Health Ministry and Family Welfare’s directorate general of health services (DGHS)
issued revised guidelines to stop the use of ivermectin and doxycycline in India [401]. The new guidelines
dropped all medicines, except antipyretic and antitussive, for asymptomatic and mild cases, while remde-
sivir was reserved only for patients hospitalized with moderate or severe disease receiving supplemental
oxygen [402]. The guidelines of the Indian Council for Medical Research (ICMR), the country’s leading
health agency in the fight against COVID-19, remained unchanged, optionally suggesting ivermectin for
outpatients.
On June 7, an article by Głuchowska et al. discussed whether parasitic diseases were protective agents
or risk factors in COVID-19, noting lower incidence of COVID-19 in most African countries, especially
those where malaria is endemic, and speculating that parasites might have also beneficial immunomod-
ulatory effects but also noting that the difference may be due to hydroxychloroquine and chloroquine
prophylaxis [403]. They however did not mention the possible effect of ivermectin prophylaxis pointed
out by Guerrero et al. [404].
On June 7, in Malaysia, a news report said a complaint had been filed accusing the health minister and
the health director-general of refusing to adopt ivermectin for COVID-19 [405].
On June 8, a news report by Birrell discussed conflicts of interest of scientific journals, suggesting that
open access journals published by Springer Nature and Elsevier depended on donations of China and
access to the Chinese market, which may have led to publication bias [406].
On June 8, in Japan, Constitutional Democrats submitted a bill to the House of Representatives to allow
use of existing drugs including ivermectin to treat COVID-19 [407].
On June 9, a news report said the US government had agreed to pay USD 1.2 billion for 1.7 million
courses (USD 700 per course) of Merck & Co/MSD’s molnupiravir, if it is proven to work in an 1,850-
patient trial expected to complete in the fall of 2021, and emergency use authorized by U.S. regulators
[408]. Other drugs in development included Pfizer’s PF-07321332 and Roche Holding AG’s AT-527.
On June 9, the chief minister of the state of Goa in India said that the government of Goa had not
purchased a single tablet of ivermectin and that it had been dropped from the treatment protocol,
despite an earlier announcement of the Health Ministry on May 10 to distribute it for mass prophylaxis
in Goa [409];[410]. Instead, a plan to vaccinate as many people as possible in the age group 18-44 years
was announced [411].
On June 12, an article by Zaheer et al. stated that potential toxicity and careful dosage analyses are
urgently required before declaring ivermectin as an anti-SARS-CoV-2 drug candidate [412].
On June 14, a Canadian newspaper published an interview of Edward Mills, the principal investigator in
the Canadian Together trial led by McMaster University, with funding for ivermectin and fluvoxamine
provided by Fast Grants [413]. Mills discussed the principles and practices of organizing clinical trials
and the possible role of repurposed medicines, criticized the FLCCC for overcalling the importance of
what they were doing, and held a neutral stance about ivermectin. He expected the ivermectin trial to
complete in a few months.
On June 14, an editorial commentary by Siedner introduced a meta-analysis by Hill et al. to be published
in the same issue [414]. The meta-analysis was said to include 24 studies and 2,127 participants for
mortality outcome. Siedner described the results as “compelling. . . suggesting a modest to large benefit
of a low-cost, widely available, well-tolerated therapy for COVID-19 – a dream scenario – but based
on studies with small sample sizes, design flaws, incomplete results, or some combination thereof”. He
worried about possible “erosion of trust in the scientific community” due to “early support for therapies
32
prior to a solid evidence base” and stressed the need for larger trials, mentioning that “the best we can
do is guess the mechanism of action”. He concluded that ivermectin might be best considered as an
extremely promising therapy not quite ready for public use; otherwise, there would be “a real risk that
the scientific community will once again be bitten by over-enthusiasm and forced to answer to a public
that will not be shy about holding us to account”.
On June 15, a review by Zaidi et al. provided an extensive review of 20 mechanisms of action of ivermectin
for SARS-CoV-2 on four levels: first, direct action on SARS-CoV-2, including action on SARS-CoV-2
cell entry, action on importin superfamily, and action as an ionophore; second, action on host targets
important for viral replication, including action as an antiviral, action on viral replication and assembly,
action on post-translational processing of viral polyproteins, and action on karyopherin (KPNA/KPNB)
receptors; third, action on host targets important for inflammation, including action on interferon (INF)
levels, action on toll- like-receptors (TLRs), action on nuclear factor-κB (NF-κB) pathway, action on the
JAK-STAT pathway, PAI-1 and COVID-19 sequelae, action on P21 activated kinase 1 (PAK-1), action
on interleukin-6 (IL-6) levels, action on allosteric modulation of P2X4 receptor, action on high mobility
group box 1 (HMGB1), action as an immunomodulator on lung tissue and olfaction, and action as an
anti-inflammatory; fourth, action on other host targets, including action on plasmin and annexin A2,
action on CD147 on the red blood cells, and action on mitochondrial ATP under hypoxia on cardiac
function. [415];[416].
On June 15, an article by Aref et al. about a RCT with ivermectin containing nasal spray in Egypt
(n=114) indicated 63.2% lower relative duration of fever (relative time 0.37, p<0.001) and 78.6% lower
risk of no virological cure (RR 0.21, p=0.004, 5.3% vs 24.6%) (NCT04716569) [417];[418].
On June 15, a commentary by Thakur in an Australian newspaper questioned the “lack of alternative
treatments” required for emergency authorization of vaccines, suggesting that a significant number of
specialists have pointed out benefits of prophylaxis and early treatment with ivermectin [419].
On June 15, adoption of ivermectin had been recently petitioned for in Namibia [420].
On June 15, a news report by NPR wrote about Brazil’s use of “unproven drugs” [421].
On June 16, a private clinic was raided in Malaysia for offering ivermectin to COVID-19 patients [422].
On June 16, FLCCC introduced a new protocol, I-RECOVER, for long haul COVID-19 syndrome (LHCS)
[423];[424]. The protocol consisted of an initial therapy with 0.2-0.4 mg/kg of ivermectin for 3-5 days,
added with 50 mg of fluvoxamine twice daily for 15 days if the patient was presenting with neurological
symptoms. If not all symptoms resolved with ivermectin, an additional corticosteroid protocol was
indicated. In case corticosteroids did not produce a resolution, suspected mast cell activation was to be
treated with low histamine diet, antihistamines and mast cell stabilizers and possibly other drugs. For
all patients, vitamin C, omega-3 fatty acids, atorvastatin and melatonin were suggested.
On June 17, a news story by Zimmer in the New York Times said the U.S. government was to invest
USD 3.2 billion to develop antiviral pills for Covid-19 and other viral diseases [425]. The new influx of
money was to speed up the clinical trials of a few promising drug candidates which were said to become
available by the end of 2021 or in a few years. The mentioned candidates included molnupiravir, AT-527
and PF-07321332. Anthony Fauci commented that “the first drugs for Covid-19 will probably only offer
modest benefit against the disease but that would be a good start”.
On June 17, an article by Krolewiecki et al. about a proof of concept RCT with 30 patients and 15
controls indicated no difference in clinical outcomes but in patients with higher median plasma ivermectin
levels there was a concentration dependent antiviral activity with mean ivermectin plasma concentration
levels correlating with viral decay rate (r=0.47, p=0.02) (NCT004381884) [426];[427]. Due to the small
number of patients and controls, the risks of mechanical ventilation and disease progression appeared
increased (p=1.00).
On June 17, an article by Bryant et al. presented a meta-analysis of 15 RCTs with 2,438 patients indi-
cating 62% lower risk of death (RR 0.38, 95% CI 0.19-0.73, n=2,438, moderate-certainty evidence) [428].
Also, low-certainty evidence from three trials indicated 86% lower risk of infection in prophylaxis (5.0%
vs 29.6%, RR 0.14, 95% CI 79-91%, n=738).
33
On June 17, an article by Gold et al. suggested that many long haul COVID-19 syndrome (LHCS)
symptoms may not be a direct result of the SARS-CoV-2 virus but the result of COVID-19 inflammation-
induced Epstein–Barr virus reactivation [429].
On June 18, an analysis by Lind et al. from the COVID-19 response team of the US Centers for Disease
Control and Prevention (CDC) analyzed ivermectin prescriptions in the US during the pandemic and
found that ivermectin dispensed from outpatient retail pharmacies increased from an average of 3,589
prescriptions per week at the pre-pandemic baseline to a peak of 39,102 prescriptions in the week ending
on January 8, 2021 (989% relative percent increase) [430]. The authors stated that clinicians should be
aware of the stances of FDA and NIH, and that better trials are needed.
On June 18, an opinion article by Royes discussed the situation in Jamaica, with the government wanting
to follow WHO’s advice in order to protect the public against possible dangers of ivermectin [431].
On June 18, an opinion article by Gordon discussed the situation in South Africa, indicating that while
ivermectin was approved for COVID-19, the process of applying for an individual permit for each patient
was unreasonably restrictive and as a result ivermectin was not being widely used [432].
On June 18, in a WHO media briefing, in a reply to a question about the possible relationship between
ivermectin home treatment kit distribution in Mexico and the decline in COVID-19 cases and deaths
(study by Merino et al. [284]), COVID-19 technical lead Maria Van Kerkhove said that the decline was
likely a result of a combination of factors, that WHO only recommends ivermectin in clinical trials,
that WHO’s clinical management team led by Janet Diaz were constantly looking at all ivermectin
studies, there were meta-analyses adding more studies as their results were becoming available, these
meta-analyses being updated regularly, and after the meta-analyses providing “robust, comprehensive
review” were updated the WHO would be looking at the recommendations again to decide what the
guideline development group “can and cannot, should and should not recommend”. She said the process
was underway and updates would be coming soon [433]. Also the chief scientist Soumya Swaminathan
pointed out that epidemiological changes were usually due to combinations of things, never due to a
single intervention, and peaks in infections had fallen for various reasons, also in countries not using
ivermectin. She said it was important to undertake properly designed studies, adding that “we must
have an open mind, and the WHO certainly has an open mind to look at each and every intervention
that could be beneficial . . . unfortunately there are not very high quality trials yet conducted about the
role of ivermectin in either prevention or treatment, and this is what our guideline development group
pointed out. When they looked at the meta-analysis, the studies were all very low quality, and therefore
what is needed is more evidence . . . we encourage more research on this .. . the jury is still out on this”.
On June 20, a news report by Jaswal analyzed the failure of Goa’s ivermectin distribution plan [434].
Earlier, the ICMR had allowed optional use of ivermectin for outpatients with a mild disease. Subse-
quently, with the intention of prophylaxis, the health minister of Goa had announced a mass distribution
of ivermectin. Goa’s political opposition soon framed the operation as a financial scam. WHO’s chief
scientist Swaminathan and a group of prominent medical institutes of hospitals announced ivermectin
should only be used in clinical trials. Petitions were filed in the high court against the plan, leading the
court to swiftly axe it. Regardless, ivermectin was available over-the-counter in Goa.
On June 20, a news report stated that Goa’s directorate of health services has instructed health centres
and hospitals across the state to remove ivermectin, zinc and doxycycline tablets from COVID-19 home
isolation kits [435].
On June 20, a 16-minute television report on Fox News featured US senator Ron Johnson and FLCCC’s
Kory presenting their view on ivermectin and censorship. Commenting the week’s announcements of US
government investing USD 3.2 billion in new antivirals for early treatment, Kory said “they will never
develop a drug that is more effective than ivermectin” [436].
On June 22, a systematic review by Murchu et al. about the effectiveness and safety of various phar-
macological and nonpharmacological interventions in the ambulatory setting, aimed at preventing severe
COVID-19, found very low certainty evidence of effect for ivermectin plus doxycycline and insufficient
evidence of effect for ivermectin monotherapy [437].
34
On June 22, a news report said that the National Agency of Drug and Food Control of Indonesia (Badan
POM) had licensed ivermectin for the treatment of COVID-19 [438]. General Moeldoko, the chief of
staff of the Executive Office of the President of the Republic of Indonesia, was said to have celebrated
the decision. In the previous weeks he had already distributed tens of thousands of doses to various red
zone locations.
On June 22, a news report from Argentina described monitoring results of 4,000 patients provided by
the ministry of health of the province of Misiones, saying that in comparison to untreated population,
ivermectin had reduced hospitalization from 4.7% to 1.2%, and mortality from 1.7% to 0.2% [439]. The
effect was dose dependent.
On June 23, a news report said Oxford University was testing ivermectin in its large-scale ‘Principle’
trial [440]. The intent to include ivermectin in the trial had initially been reported on January 23 [441];
[442].
On June 23, Warren Buffett announced his resignation as the trustee at the Bill and Melinda Gates
Foundation, describing his previous role as the trustee as “inactive” [443].
On June 24, emeritus professor Robert Clancy, an immunologist at the University of Newcastle, backed
ivermectin as a COVID-19 treatment [444].
On June 24, an article by Yuce et al. determined ivermectin as a Mpro inhibitor candidate to be evaluated
against SARS-CoV-2 infections [445].
On June 25, an article by Dias de Melo et al. about an animal study showed that standard doses of
ivermectin prevented clinical deterioration, reduced olfactory deficit, limited the inflammation of the
upper and lower respiratory tracts but had no effect on viral load in the airways in SARS-CoV-2-infected
hamsters [446]. It dampened type-I interferon responses, and dramatically reduced the IL-6/IL-10 ratio
in lung tissue and promoted macrophage M2 polarization.
On June 25, in a video interview professor of biochemistry and molecular biology Gordan Lauc, an
official advisor to the Croatian government on pandemic management strategy, discussed, among other
subjects, COVID-19 testing [447]. Lauc commented that he continuously wondered what the reason was
for all the fear-inducing propaganda which overestimated mortality, adding that “for example in Croatia
I have reasonable influence: I’m a formal advisor of the prime minister. When I look into into this
information which is being distributed to the media, most of the times it can be attributed to people
who are actually making a lot of profit in this pandemic because this testing industry has become maybe
the largest industry in the world. It’s a huge amount of tests. Croatia is at the bottom of Europe by
the number of tests that we are doing, yet we have already spent maybe USD 250 million on testing. I
have a PCR laboratory, I know the technology. The raw cost of testing is virtually zero, so the the kit
producers, distributors, laboratories all make a profit. There is a 90% profit margin on all levels. I think
this is one of the reasons why people want to keep this going. Because when you have this huge amount
of profit just accumulated, you can easily use it to persuade some of the scientists or journalists to go
your way. I’m not sure about politicians. I think that every politician wants to be successful. Yet now
they all try to strangle their own countries. It is going on with the economies all around Europe and
it is going to be a disaster. If you look at what is happening in the US, it is exploding with recovery,
and China.. I don’t know what will happen to Europe in the end. And we did it to ourselves”. The
interviewer described the situation as “an unscientific or anti-scientific mass delusion . . . people going
into politics are not the hardcore nerdy technical types. It’s the opposite. We know what their talents
are, and they’re not technical. So the politicians are ripe to be misled”.
On June 25, in a news report, WHO’s representative in Malaysia rehearsed WHO’s stand on ivermectin:
inconclusive evidence of efficacy, very low certainty of this evidence, ivermectin being recommended only
in the context of a clinical trial, guidelines being developed by a group of independent experts, trials
ongoing, and ivermectin potentially having adverse effects including seizures, coma and even death [448].
On June 25, a survey of 1,055 physicians in 24 states of India indicated that one third had used ivermectin
for COVID-19 [449].
On June 26, a news report indicated that the Medicines Control Authority of Zimbabwe (MCAZ) had
authorised doctors to prescribe ivermectin for COVID-19, on the condition they record patient symptoms
35
and adverse effects and report them monthly [450];[451];[452]. One interviewed local physician welcomed
the regulations but criticized the Medical and Dental Practitioners Council of Zimbabwe (MDPCZ) for
arresting a doctor [Jackie Stone] who had been a key figure among early adopters of ivermectin in
Zimbabwe. The physician said “many deaths could have been avoided if the regulatory authorities had
paid attention to the science as opposed to parroting the WHO and pharmaceutical vested interests”,
adding that “the evidence has been there for a while and we know ivermectin works from local treatment
done by some courageous doctors”. He also commented that MCAZ had continuously resisted adoption
of ivermectin but had recently been forced to backpedal because of pressure from the government which
was seeing the evidence as it had moved out of medical circles into the mainstream. The physician asked
why MCAZ had instigated the arrest and humiliation of a doctor despite dozens of studies and a meta-
analysis showing ivermectin’s efficacy and added that now when Oxford University and the Americans
were coming on board, the regulators had suddenly realized the monumental mistake they had made
and the risk to their credibility". He said they welcomed the development but were quite disappointed
about how studies had previously been ignored and lives lost unnecessarily.
On June 28, a news report indicated an apparent reversal of Zimbabwe’s ivermectin policy announced a
few days before, saying the health regulator will only allow it for research [453].
On June 28, an article by Roman et al. presented a meta-analysis of ten RCTs including 1,173 patients
with mild or moderate disease [368]. The authors wrote that in comparison to standard of care or
placebo, ivermectin did not reduce all-cause mortality, length of stay or viral clearance. They concluded
that ivermectin was not a viable option to treat COVID-19 patients. The article was based on a previous
preprint [382];[383].
On June 29, Fordham, one of the authors of the March 2021 ivermectin meta-analysis by Bryant et al.
[15], discussed their rejected submission of it to Lancet Respiratory Medicine, their earlier attempt to
publish it as a Cochrane review, and related issues [454].
On June 30, the latest meta-analysis of 60 ivermectin studies by CovidAnalysis group indicated similar
improvements than their March 31 meta-analysis of 49 studies [455]. The improvements in March vs
June were 89% vs 85% in prophylaxis, 80% vs 76% in early treatment, 50% vs 46% in late treatment,
and 72% vs 71% all together.
Discussion
In the United States and the European Union, most of the year 2020 appeared to have been characterized
by an attempt to collect ivermectin-related data. The period from the beginning of November 2020 to
the end of March 2021 appeared to be characterized by disputes about interpretation of this data. The
change of administration in the United States did not appear to significantly change its ivermectin-
related health policy, likely to the disappointment of ivermectin proponents. Beginning from the March
30 guideline decision by the WHO against ivermectin, a period of a kind of trench warfare appeared to
emerge. Ivermectin proponents, especially the FLCCC, announced they had resigned their attempts to
influence the US National Institutes of Health, the Food and Drugs Agency, the European Medicines
Agency and the World Health Organization. Similarly, the BIRD group turned directly to clinicians
and the public. Changes to existing treatment protocols were mostly minor. Fluvoxamine emerged
as an option and was added to many protocols including the FLCCC’s. The FLCCC introduced two
new protocols: the I-MASS protocol for mass prophylaxis and the I-RECOVER for long haul COVID-19
syndrome (LHCS). An interesting new development was the recognition of the role of mast cell activation
and histamine release in LHCS [456].
The US NIH announced a new trial, ACTIV-6, for repurposed medicines, estimated to finish in March
2023, almost two years in the future, rendering the trial practically irrelevant for the purposes of handling
the pandemic. Simultaneously, pharmaceutical companies continued their attempts to finish their trials
of new outpatient treatment pharmaceuticals as swiftly as possible, and new projects for the development
of such treatments were initiated in the US and the UK.
A third concurrent process was the slower-than-expected progress of vaccination programs. A fourth
concurrent process was the adoption of ivermectin in countries outside the US and EU. The countries who
36
had adopted ivermectin previously, including Slovakia, implicitly disregarded the March 2021 guideline
set by the WHO [171];[457]. India adopted ivermectin nationally after the announcement of the WHO
guideline, then mostly dropped it, with the current situation being somewhat unclear. Legal action
against the WHO was initiated in India. At the end of the period, Indonesia adopted ivermectin.
With regard to researchers and clinicians, medical professionals whose practices appeared to be predom-
inantly based on following existing regulations and protocols appeared to feel criticism against them
unjustified and unfair. Similarly, medical professionals whose interest was in the further development of
the protocols felt criticism against them unjustified and unfair. The first group may have perceived the
latter group as deviants, whereas the latter group may have perceived the first group as anti-innovative.
Presumably, both groups saw each others’ practices as somewhat unethical and antisocial. The difference
was possibly due to different perspectives on collegiality and the perception of the role of patients. The
first group appeared to put more weight on collegial cohesion and rule-adherence, with less weight put
on individual patient outcomes, assumedly perceiving that patient outcomes were predominantly the
product of the inflexible regulations which lay beyond their responsibility. The second group appeared to
put less weight on collegial cohesion and regulations, placing more weight on individual patient outcomes,
assumedly perceiving that patient outcomes superseded the rules and that validation of rules was the
responsibility of individual clinicians.
With regard to COVID-19, knowledge about the mechanisms and treatments was somewhat scarce
especially in the early phase of the pandemic. A recent study described that in such a situation, it would
be adaptive to seek further information to resolve uncertainty and obtain a more accurate worldview but
biases in such information-seeking behavior could contribute to the maintenance of inaccurate views [458].
The study indicated that more dogmatic individuals were less likely to seek out new information to
refine an initial perceptual decision, leading to a reduction in overall belief accuracy despite similar
initial decision performance. In addition, dogmatic participants placed less reliance on internal signals
of uncertainty, rendering them less likely to seek additional information to update beliefs derived from
weak or uncertain initial evidence. Dogmatism is often defined as a viewpoint or system of ideas based on
insufficiently examined premises. Thus, differences in openness to research evidence may have been due
to differences in personalities and habits which, in turn, may be seen as products of the life experiences
(environments) of the individuals, including their medical education.
At times, the views appeared to differ up to a point in which the existence of a shared reality could be
questioned, and the practice of presenting opposite conclusions on the same, existing data was in effect
making further research irrelevant.
Validity of statistics-based research
In the context of clinical trials, the fundamental validity of the statistics-based research in general is
rarely discussed. In 2011, Penston said that the extent and depth of the criticisms of statistics-based
research usually comes as a surprise to investigators, doctors and other health care professionals who
use the data from large-scale RCTs and epidemiological studies, as they rarely have the time, inclination
and skill to read the related literature [459]. He questioned the large size of a study as a sign of strength,
saying that as the number of patients recruited to a study increases, statistical significance may be
achieved but causal inference is weakened, adding that the source of the problem was the belief that
causal relationships of value can be derived from extremely heterogeneous samples. He also said that
the methodology of statistics-based research cannot be tested independently of statistics; therefore it is
unknown whether the causal inferences drawn from the data of large-scale RCTs and epidemiological
studies are valid. According to him, lack of understanding of diseases and the properties of drugs, i.e.
ignorance, were driving up the size of studies, and we had witnessed “an inexorable increase in the size
of epidemiological studies and RCTs over the past 50 years without any concern for the consequences”.
Saint-Mont discussed the effect of randomization, detailing various false assumptions related to it, con-
cluding that randomization does not lift experimental procedures in the medical and social sciences to
the level of classical experiments in the natural sciences but may lull researchers into a false sense of
security instead [460]. Both Saint-Mont and Penston stressed the importance of the existence of sound
background theory as crucial for the success of science. Theory allows for stricter definitions of concepts
37
and the identification of homogeneous reference classes that ensure regularity and, hence, reliable causal
inference. In the context of COVID-19, the FLCCC appeared to present their conclusions more in the
context of background theory (especially the MATH+ protocol [77]), while most others appeared to rely
more on statistics.
An alternative or adjunct to RCTs to investigate could be causal modeling [461];[462];[463];[464].
According to Sgaier et al., causal modeling allows testing for causality in individuals and population
groups faster and more efficiently, along with the ability to unravel the underlying complexity, and
allows researchers and program designers to simulate an intervention and infer causality by relying on
already available data [461]. Karvanen has provided examples of causal models for a case-control study,
a nested case-control study, a clinical trial and a two-stage case-cohort study [463].
Journalistic ethics
With regard to journalistic ethics, the censorship discussion of April 11 appeared to indicate that jour-
nalistic principles that should have been self-evident no longer were, such as the responsibility of the
media “to tell the truth” [165]. As described already for the period preceding April 2021, the financial
press (e.g. the Wall Street Journal [163] and the Financial Express [171]) seemed to be more in favor of
repurposed medicines, whereas the generalist press mostly continued to ignore or oppose them [217].
MacLeod has written about practices of the mass media in the United States, stating that corporate
shareholders have no interest in the veracity of the news, only in short-term profits, and that reporting
that challenges corporate profits is strongly discouraged [465]. A key factor shaping the content of the
media is its reliance on advertising from large businesses for revenue. Advertisers wish to appeal to the
groups and individuals with a greater spending power and to avoid controversial and critical content.
Also, the collapse in advertising revenue in the traditional media has led to an increasing dependence
on official sources, government and corporations which effectively subsidize the media by providing free
content but expect something in return. In addition, in many cases, journalists are preselected based
on their obedience to authority and their credulousness, and they increasingly come from the elite
themselves [466]. The media houses also depend on social media for visibility which may be easily denied
of them. Yet another factor are ideologies which in the United States were traditionally anti-communist
but more recently anti-Trump and anti-Russian, for example. In the US media, ivermectin was often
associated with hydroxychloroquine, and hydroxychloroquine with president Trump [467].
The dismissal of ivermectin in the press appeared to be related to the Trusted News Initiative (TNI)
founded by Associated Press (AP), Agence France-Presse (AFP), British Broadcasting Corporation
(BBC), Canadian Broadcasting Corporation (CBC), European Broadcast Union (EBU), Facebook, Fi-
nancial Times, First Draft, Google, YouTube, The Hindu, Microsoft, Reuters, Twitter and Washington
Post [321]. TNI appeared to function as some kind of peer-to-peer structured censorship mechanism.
Social media fact-checkers
In its COVID-19 medical misinformation policy, YouTube explicitly forbade treatment misinformation
including “content that recommends use of ivermectin or hydroxychloroquine for the treatment of COVID-
19” and “claims that ivermectin or hydroxychloroquine are effective treatments for COVID-19” [468]. The
policy forbade also a large amount of peer-reviewed medical publications, in effect making YouTube an
anti-science organization.
In a similar manner the policy forbade “prevention misinformation”, explicitly defined as “content that
promotes prevention methods that contradict local health authorities or WHO”, specifically mentioning
“content that recommends use of ivermectin or hydroxychloroquine for the prevention of COVID-19”. It
also explicitly disallowed discussions of efficacy and possible adverse effects of vaccines which “contradict
expert consensus from local health authorities or WHO”. Also diagnostic, transmission, social distancing
and self-isolation information contradicting local health authorities or WHO were banned. The defini-
tions of “expert” and “consensus” remained undefined, making the policy arbitrary, subsequently making
YouTube an unpredictable promoter and enforcer of possibly arbitrary or authoritarian practices. In
addition, technically, where local health authorities and WHO disagreed, application of the “or” operator
38
banned content contradicting with either of them. Therefore in countries such as Slovakia and India,
YouTube could not be used for content that recommended either for or against ivermectin for prophylaxis
of COVID-19.
Clarke mentioned that YouTube and Facebook were relying on third party fact checkers funded partly
by Charles Koch Institute [373];[374];[372]. Koch was listed as one of the 18 major funders of Poynter
Institute, each with an undisclosed sum of at least USD 50,000, making it impossible to compare funders’
contributions [469];[470]. The International Fact-Checking Network (IFCN) is a unit of the Poynter
Institute [471]. In May 2020, Facebook stated that all of its fact-checking partners were certified by
IFCN [472]. IFCN stated it led an alliance of over 100 fact-checkers [473]. Poynter Institute described
that the alliance was launched in January in response to “rampant misinformation globally” which the
WHO classified as an “infodemic”, with the alliance “on the front lines in the fight against it”.
IFCN and the alliance also maintained a database of checked facts [474]. The database was updated
daily, with members collaborating on the “massive crowdsourcing project” by using a shared spreadsheet
and instant messaging apps. Poynter said the international collaboration had allowed the members to
respond faster and reach larger audiences. All of the over 80 items found in the database with search
term “ivermectin” dated between April 2020 and May 2021 were labeled either as no evidence, unproven,
exaggerated, misleading, missing context, partly false, or false (the most common label), with two items
labeled as explanatory [474]. Most of the items originated from South American partners such as Estadão
Verifica in Brazil.
Some of the other major funders of Poynter included Facebook, Google News Initiative [475], Foundation
to Promote Open Society (FPOS) of George Soros, a primarily US government funded agency National
Endowment for Democracy (NED) [476], Democracy Fund created by eBay founder Pierre Omidyar,
funding especially PolitiFact [477], and the Omidyar Network/Luminate also of Omidyar, Craig New-
mark Foundation of Craigslist founder Craig Newmark, with at least USD 6 million donated to Poynter
Institute [478], and Rita Allen foundation involved in medical research, with its stated goal of “inves-
ting in transformative ideas in their earliest stages to promote breakthrough solutions to significant
problems” [479].
It was of note that the major funders of Poynter included several individuals who were billionaires.
Assumedly, they may have possessed influence over guidelines for what qualified as “facts”. While there
was not enough information to ascertain whether the observed patterns of social media censorship were
related to the values and previously observed practices of the any of the funders specifically, it was also
not possible to rule out such influences.
An example may illustrate what kind of issues may arise from the use of donations as a tool for gaining
political influence. With regard to funding by Koch, a report by Mayer in the New Yorker described the
Koch brothers as “longtime libertarians who believe in drastically lower personal and corporate taxes,
minimal social services for the needy, and much less oversight of industry .. . their combined fortune of
thirty-five billion dollars is exceeded only by those of Bill Gates and Warren Buffett . . . many of the
organizations funded by the Kochs employ specialists who write position papers that are subsequently
quoted by politicians and pundits. David Koch has acknowledged that the family exerts tight ideological
control. ‘If we’re going to give a lot of money, we’ll make darn sure they spend it in a way that goes
along with our intent .. . and if they make a wrong turn and start doing things we don’t agree with, we
withdraw funding’ ” [480];[481].
A republican political consultant commenting Kochs’ strategies for opposing climate change related oil
industry reforms said that “the key .. . was to question the science – a public-relations strategy that
the tobacco industry used effectively for years to forestall regulation”. As an example of health related
interests, David Koch had served on the US National Cancer Advisory Board without disclosing his
conflicts of interests as a major producer of formaldehyde, while simultaneously lobbying to prevent the
US Environmental Protection Agency (EPA) from classifying formaldehyde as a carcinogen, and funding
members of Congress who had stymied the EPA, requiring it to defer new regulations until more studies
would be completed.
Mayer’s article described Kochs’ operations as “covert”, referring to David Koch’s description of their
businesses as “the largest company that you’ve never heard of”. According to SourceWatch, in addition to
39
denying climate change, other issues on the Kochs’ agenda included repealing health reform (Obamacare),
dismantling collective bargaining rights, fighting reductions in carbon emissions, keeping corporate money
in elections and fighting internet neutrality [482];[483]. With regard to COVID-19, Koch Industries were
producing test kit materials, sanitizers, alerting systems, healthcare IT systems related to COVID-19
diagnostic testing, ventilators, and personal protective equipment [484].
Poynter’s largest custom training partners in 2019-2021 included Facebook, Huffington Post, Market-
place, MRC Media, Middle East Broadcasting Networks, National Public Radio (NPR), Newsweek, New
York Times, Southern Newspapers Publishers Association, Washington Post, TikTok, USA Today Net-
work, Vice and Voice of America [469].
Academic journals
Regarding the academic journal publisher Frontiers Media SA’s, one of the members of its board of
directors responsible for the financial and governance oversight of the company was Steve Koltes, founder
and co-chairman of CVC Capital Partners Ltd [485]. In 2019, CVC Capital Partners, one of the world’s
largest private equity and investment advisory firms, was said to have USD 75 billion of assets under
management [486]. CVC announced that a group of its executives had helped fund University of Oxford’s
vaccine research [487];[488]. CVC had also invested in System C, a company providing key software being
used for planning and managing the UK’s COVID-19 vaccination programme [489]. The Times described
CVC as “powerful, successful and extremely low profile” [490].
In 2015, Frontiers had removed 31 editors after the editors had complained that company staff were
interfering with editorial decisions and violating core principles of medical publishing [491].
The WHO
During the period, an intensifying critique of the WHO emerged as a result of the March 2021 iver-
mectin guideline lacking transparency and breaking established practices of meta-analysis and research.
Presenting criticism towards the feasibility of the vaccines-only approach and its possible relationship
to financial interests of the pharmaceutical industry, or possible failures of entities such as WHO, FDA,
NIH and EMA, has been difficult during the pandemic. Regardless, it is necessary to consider whether
funding-related biases might exist with regard to the current practices of these agencies, especially the
WHO.
First we may note that the main funders of the WHO for the 2018/2019 biennium were United States
(USD 893 million), Bill and Melinda Gates Foundation (USD 531 million), United Kingdom (USD
435 million), Gavi The Vaccine Alliance (USD 371 million), Germany (USD 292 million), Japan (USD
214 million), UN Office for the Coordination of Humanitarian Affairs (UNOCHA) (USD 192 million),
Rotary International (USD 143 million), World Bank (USD 133 million), European Commission (USD
131 million), National Philanthropic Trust (USD 108 million), Canada (USD 101 million), China (USD
86 million), Norway (USD 86 million), UN Central Emergency Response (USD 86 million), Sweden (USD
77 million), France (USD 76 million), Kuwait (USD 70 million), Republic of Korea (USD 70 million) and
Australia (USD 67 million) [492];[493];[494].
The Bill and Melinda Gates Foundation stated that its focus was on vaccine equity [307]. Also Gavi The
Vaccine Alliance had been founded by the Bill and Melinda Gates Foundation in 1999, and the Gates
foundation had invested a total of USD 4 billion in Gavi [495]. Gavi described the Gates foundation as
“a key Gavi partner in vaccine market shaping”. The Gates Foundation also had long-term partnerships
with Rotary International (polio vaccinations), National Philanthropic Trust, and the World Bank. To-
gether, the USD 902 million contributions of the Gates Foundation and Gavi exceeded the United States
contributions of USD 893 million, making the Gates-Gavi cluster the largest funder of the WHO in the
2018/2019 biennium (in April 2020, president Trump announced that US halted funding to the WHO;
the effects of this remained unclear [496];[497]). In addition, the Global Fund to Fight AIDS, Tuberculo-
sis and Malaria (GFATM) contributed 33 million. Co-founded by the Bill and Melinda Gates Foundation
in 2002, the foundation has contributed a total of USD 2.49 billion to GFATM [498].
40
Considering the recent USD 4 billion donation by the United States government to Gavi [89], one inter-
pretation of the situation might be that the US outsourced a large part of its public health policy setting
to Gavi and, subsequently, to Gates.
Yet another member of the Gates cluster was the Seattle-based PATH (Program for Appropriate Tech-
nology in Health), one of the largest nonprofit organizations in global health [499]. In 2021, its website
presented with a banner saying “600 million people are vaccinated. 7 billion haven’t had a shot. Help
PATH today”. PATH’s CEO Nikolaj Gilbert, previously the global partnerships director for the Uni-
ted Nations Office for Project Services (UNOPS) and an employee of Novo Nordisk, described PATH’s
priorities: “the partnership with the Bill and Melinda Gates Foundation and the U.S. government has
shaped what this organization is all about today .. . so one of my key priorities will be to see: how can
we sustain and grow those relationships that we have, how can we continue to be the preferred partner
for those donors, and how can we also help them with their priorities?” [499].
A 2017 Politico article described Gates as “the world’s most powerful doctor”, saying his sway over the
WHO spurred criticism about misplaced priorities and undue influence [500];[501]. The article quoted
Gates’ critics saying that “Gates’ priorities have become the WHO’s . .. he is treated liked a head of state,
not only at the WHO, but also at the G20”. Top WHO officials were said to have raised concerns that
the foundation was distorting research priorities. Over three quarters of the WHO’s budget was coming
from voluntary contributions which were usually earmarked for specific projects or diseases so that the
WHO could not freely decide how to use them. The article stated that the Gates foundation’s focus on
delivering vaccines and medicines, rather than on building resilient health systems, had drawn criticism.
Changes had been made to the WHO’s budget approval process to in order to decrease the foundation’s
influence. Yet a senior fellow for global health at the Council on Foreign Relations commented that “the
foundation’s impact on the WHO is enormous . . . if they weren’t there, if they walked away with their
money, the deleterious impact would be profound, and everyone is all too aware of that”.
Importantly, it should also be noted that the other top 20 funders predominantly represent high-income
countries of the North America and Europe. None of the countries that had officially adopted ivermectin
country-wide for COVID-19 up to April 2021 were represented [502]. Similarly, Coalition for Epidemic
Preparedness Innovations (CEPI), an organization aiming to accelerate the development of vaccines
against emerging infectious diseases and enable equitable access to these vaccines for people during
outbreaks was founded by the governments of Norway and India, Bill and Melinda Gates Foundation,
UK Wellcome Trust, and the World Economic Forum [503]. It had later secured financial support from
Australia, Austria, Belgium, the Bill and Melinda Gates Foundation, Canada, Denmark, the European
Commission, Ethiopia, Finland, Germany, Hungary, Iceland, Indonesia, Italy, Japan, Kuwait, Lithuania,
Luxembourg, Malaysia, Mexico, Netherlands, New Zealand, Norway, Panama, Romania, Saudi Arabia,
Serbia, Singapore, Switzerland, The Republic of Korea, United Kingdom, USAID, and UK Wellcome
Trust. Of these countries, as of June 2021, ivermectin had been officially adopted in Mexico, Panama
and Indonesia, as well as mixed use or occasional off-label use in some other countries [502].
Additionally, CEPI had received support from undeclared private sector entities as well as public con-
tributions through the UN Foundation COVID-19 Solidarity Response Fund [503]. Each investor was to
get one representative to an Investors Council providing guidance and oversight of CEPI activities, with
four members serving on the CEPI board. Another entity, a Joint Coordination Group, was intended to
discuss how to best enhance CEPI’s efforts to deliver and deploy vaccines, and had a role in planning for
rapid response to a priority pathogen or an unknown pathogen. The Joint Coordination Group inclu-
ded the WHO, Gavi, European Medicine Agency (EMA), United States Food and Drug Administration
Agency (FDA), Médecins Sans Frontières (MSF), UNICEF, International Federation of Red Cross and
Red Crescent Societies (IFRC), African Vaccine Regulatory Forum (AVAREF), UK National Institute
for Biological Standards and Control (NIBSC) and UK Wellcome Trust. The Wellcome trust had been
previously found out to secretly invest in companies that contributed to the same problems the trust
said it wanted to solve [504]. The trust’s known investments through offshore companies in the Cayman
Islands amounted to USD 891 million in 2018.
In 2010, the Bill and Melinda Gates Foundation, Gavi, WHO, US NIH/NIAID, CDC, UNICEF, PAHO
and several research organizations launched a Decade of Vaccines collaboration, initiated by the Ga-
tes Foundation [505]. The intention was to enable greater coordination across all stakeholder groups –
41
national governments, multilateral organizations, civil society, the private sector and philanthropic orga-
nizations. The five-member leadership council included the director general of WHO, Anthony S. Fauci
of the National Institute of Allergy and Infectious Diseases (NIAID), executive director of UNICEF, an
representative of African Leaders Malaria Alliance, and the president of global health at the Bill and
Melinda Gates Foundation. All the relevant organizations had thus intimately and for the long term
participated in the vaccine-centric collaboration initiated by Gates.
According to a recent study, in 2020, governments had spent a total of EUR 93 billion on COVID-19
vaccine and therapeutics development projects, with 95% allocated to vaccines and 5% on therapeu-
tics [506]. 32% of the funds came from the US, 24% from the EU, and 13% from Japan and South
Korea (a total of 69%). Only 7% of funds were preferred loans or conventional grants. 93% were advance
market commitments (AMCs), i.e. binding agreements to subsidize purchases of vaccine doses prior to
availability. Interestingly, 71% of the vaccine funding was allocated to Small and Medium Enterprises
(SMEs) and MidCaps, with only 18% allocated to large pharmaceutical manufacturers. The figures did
not include private sector investments.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership
program initiated by the US National Institutes of Health aimed at developing a coordinated research
strategy for prioritizing and speeding development of the most promising treatments and vaccines [228].
Its public partners included Biomedical Advanced Research and Development Authority (BARPA), Cen-
ters for Disease Control and Prevention (CDC), Department of Defense, Department of Veterans Affairs,
European Medicines Agency (EMA), National Institutes of Health (NIH), The Operation (formerly
known as Operation Warp Speed), and US Food and Drug Administration (FDA). Industry partners
included AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Dewpoint Therapeutics, Eisai, Eli Lilly
and Company, Gilead, GlaxoSmithKline, Johnson & Johnson, Merck & Co/MSD, Moderna, Novartis,
Novavax, Pfizer, Rhythm Therapeutics, Roche-Genentech, Sanofi, Takeda, and Vir Biotechnology. Non-
profit partners included Bill and Melinda Gates Foundation, Fred Hutchinson Cancer Research Center,
Foundation for the National Institutes of Health, and RTI International.
According to the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA),
as of February 2021, there were approximately 382 vaccine candidates in development, of which 24 in
Phase I, 34 in Phase II and 23 in Phase III [507]. In addition to vaccines, there were over 1,000 clinical
trials for therapeutics, of which 190 in Phase III. For example, Eli Lilly and Company and the Bill and
Melinda Gates Foundation had entered into an agreement to facilitate access to future Lilly therapeutic
antibodies under development, to benefit low- and middle-income countries.
According to Schwab, in five years up to 2020 the Gates Foundation had invested at least USD 250
million in companies that were currently working on COVID-19 vaccines, therapeutics, diagnostics or
manufacturing [508];[509]. Hel also noted that Wellcome Trust had invested at least USD 1.25 billion
to COVID-19 related industries [510]. Both funders were thus positioned to potentially gain from the
pandemic financially. Wellcome’s director had a position on the Scientific Advisory Group for Emergencies
advising the UK government on COVID-19, as well as a board seat on the Coalition for Epidemic
Preparedness Innovations (CEPI). Earlier, the UK’s Scientific Advisory Group for Emergencies had
failed to publicly disclose competing interests related to COVID-19. A Canadian professor emeritus
of health policy and management commented that the funders were assumedly “acting the way they
always have .. . looking after their own financial interests [and] pursuing their own privately developed
objectives without being responsible to anybody but their own boards of directors”. Schwab said that
despite the outsize role of the private charities in the pandemic response their financial interests had
been little scrutinized, likely because foundations were not subject to the same oversight mechanisms as
public institutions. A professor of sociology in the UK commented that the foundations were giving a
false ideological impression that they are solving the problem even when they’re not.
The Gates foundation had also donated almost USD 2 billion to for-profit businesses, including USD 89
million to Novavax Inc., USD 65 million to GlaxoSmithKline Biologicals, USD 63 million to Evotec and
Just Biotherapeutics, USD 61 million to Biologial E. Limited, USD 53 million to LG Chem Ltd., USD
43 million to Dimagi Inc, USD 40 million to Inventprise, USD 38 million to Bharat Biotech International
Ltd., USD 37 million to Janssen Vaccines and Prevention BV, and USD 35 million to AJ Vaccines
AS [510]. Schwab claimed the foundation was subsidizing private companies’ research costs, opening up
42
markets for their products, and bankrolling their bottom lines. He also claimed the foundation had funded
groups pushing for industry-friendly government policies and regulation, including the Drug Information
Association. He was also said to have funded nonprofit think tanks and advocacy groups that wanted to
limit the role of government or direct its resources toward helping business interests. Schwab also noted
that despite having given away USD 23.5 billion in the last five years up to 2020, Bill and Melinda Gates
Foundation’s income from its investments had exceeded USD 28.5 billion in the same period [510].
Other commentators asked whether the Gates Foundation was addressing or reinforcing systemic pro-
blems raised by COVID-19, citing lack of transparency, dogmatic defence of intellectual property rights
and monopolies, and intimate involvement with large pharmaceutical corporations as the main issu-
es [511]. A 2016 report by Curtis gave details about Microsoft’s tax avoidance practices and its mono-
polistic nature, the foundation’s excessive global influence and support to various questionable practices
including industrial agriculture with patented genetically modified seeds, Gates family’s “considerable
personal access to senior levels of the WHO”, Gavi’s alleged overpaying for vaccines leading to excessive
increases in vaccine prices, Gates’ dismissal of the issue, and the foundation’s agenda skewing health
priorities and distorting health programmes [512]. Curtis wrote that one problem with the foundation’s
heavy focus on developing new vaccines was that it detracted from other, more vital health priorities such
as building resilient public health systems. As a rationale, Gates was said to have provided the following:
“Vaccines are an extremely elegant technology. They are inexpensive, they are easy to deliver, and they
are proven to protect children from disease. At Microsoft, we dreamed about technologies that were so
powerful and yet so simple.. . all 193 member states, you must make vaccines a central focus of your
health systems”. Curtis commented that Gates had “a fixation on vaccines”. He also claimed the foun-
dation was stifling criticism through its media and NGO influence built on donations. An US professor
of media, culture and communications was quoted saying the foundation “wielded enormous propaganda
power”. A 2009 editorial in the Lancet, describing the foundation’s governance principle of being “driven
by the interests and passions of the Gates family” as “whimsical”, proposed that the foundation should
be more transparent and accountable and listen to opinions of external parties [513];[514].
In April 2020, the Bill and Melinda Gates Foundation awarded a five-year grant of USD 50 million to
Unitaid to fight against HIV, tuberculosis and malaria, in addition to previous contributions of USD 100
million since 2006. Unitaid’s budget for the year 2021 was approximately USD 32 million [515]. In late
2020, Unitaid partially funded the ivermectin meta-analysis by Hill et al. published as a preprint [16].
This meta-analysis was later ignored by the WHO in its March 2021 decision against the use of ivermectin
except in clinical trials [6]. On April 22, the chief of Unitaid stressed the need to increase commercial
research and development of new pharmaceuticals for the treatment of COVID-19 [242]. A core function
of Unitaid is Medicines Patent Pool, a tool or practice to negotiate patents for low-income countries;
this emphasis may have made unpatentable products seem foreign to the organization [516];[517]. Gates
foundation was the chair of Unitaid’s Finance and accountability committee and a member of its policy
and strategy committee [518].
Comparing the countries most heavily involved in the development and funding of vaccines to the coun-
tries with interest in ivermectin it can be noted that the two sets of countries have little overlap. Also, it
can be noted that if influence is related to the amount of funding given, the first set of countries likely
had more influence in the WHO in comparison to the rest of the countries.
Comparing the countries most heavily involved in the development and funding of vaccines to the coun-
tries with interest in ivermectin it can be noted that the two sets of countries have little overlap. Also, it
can be noted that if influence is related to the amount of funding given, the first set of countries likely
had more influence in the WHO in comparison to the rest of the countries.
The WHO, the philanthropic entity Bill and Melinda Gates Foundation, the public-private partner-
ship Gavi The Vaccine Alliance, and the philanthropic-commercial entity CEPI appeared to be strongly
interconnected with each other and with high-income nation states. Major financial investments and
commitments likely created propensities for various biases and a vulnerability to the sunk cost falla-
cy [519]. A haphazard or ideological commitment solely to vaccines (95% of government spending) may
have overlooked considerations of cost-effectiveness and feasibility, such as vaccines likely being more
expensive and more vulnerable to viral variants than repurposed medicines, their long-term safety being
unclear, and vaccines likely requiring constant redevelopment and revaccinations, in addition to not being
43
suitable for self-administration and requiring refrigerated delivery systems. With regard to the sunk cost
fallacy, it would be more economical for the governments to reconsider the vaccine and investigative
pharmaceuticals dominated pandemic policy and at least adjunct it with broad-spectrum repurposed
medicines.
Comparisons to the H1N1 pandemic
After the H1N1 ‘swine flu’ pandemic of 2009-2010, the WHO was accused of malpractice when conflicts
of interests of key WHO scientists led to unfeasible WHO recommendations which in turn led to billions
of public money spent on inefficacious antivirals for H1N1 influenza [520];[521];[522];[523]. In her
book, Abeysinghe has written about the role of the WHO [524]. A review by Andres summarizes key
points, including the monopoly of the WHO to declare a pandemic [525]. In the case of H1N1, WHO was
retrospectively criticized for unnecessarily declaring a pandemic, as for example the European Centre
for Disease Control (ECDC) did not agree that the disease should be qualified as severe (measured by
mortality), which at the time was considered a requirement for a pandemic but is no longer mentioned.
At the time, an epidemiologist commented that the WHO, public health officials, virologists and phar-
maceutical companies had “built this machine around the impending pandemic . . . there’s a lot of money
involved, and influence, and careers, and entire institutions .. . all it took was one of these influenza
viruses to mutate to start the machine grinding” [526].
WHO was later criticized by the Council of Europe for giving too much importance to vaccination and
for not sufficiently emphasizing other measures such as the use of antivirals even though some arguments
suggested that other measures, such as taking antivirals preventively, could be at least as efficacious as
vaccines [525];[521];[522]. WHO emphasized mass vaccination as the most effective strategy against
H1N1 [524]. According to Abeysinghe, this emphasis was a result of the path-dependent institutional
reaction of the organization, where prior experience with infectious disease (including notable victories
using mass vaccination strategies) resulted in the favoring of this reaction, whereas other potential actions
were disregarded or underemphasized.
In June 2010, the rapporteur of Council of Europe Parliamentary Assembly described the acts of the
WHO as foolish, saying “this is not going to go away” [524]. The rapporteur assumedly meant the
criticism was not going to go away; yet it appears instead that the organizational patterns did not go
away, leading the WHO and the national governments to repeat the same issues a decade later in the
COVID-19 pandemic.
Legal responsibility of public-private partnerships and the WHO
Clarke has noted that the regulation of global health has partially shifted from the hands of states
and international organizations into the hands of public-private partnerships such as Gavi The Vaccine
Alliance and the Global Fund [527];[528]. These partnerships then become capable of also adversely
impacting the rights of individuals, leading to concerns of responsibility under international law. However,
the private entities in public-private partnerships typically fall outside the framework of responsibility
under international law, and thus cannot be held responsible under it. In addition, in certain instances
the partnerships have been granted immunity from the jurisdiction of domestic courts. This immunity
applies to the staff, funds, properties and assets of these partnerships. The situation regarding Gavi and
the Global Fund appeared especially complicated and the legal details were therefore considered out of
the scope of this review.
With regard to the WHO, Gostin has described WHO’s regulatory powers as extraordinary, noting that
it may set regulations on a broad range of health topics including the safety, potency, and advertising
of biologicals and pharmaceuticals, and a nomenclature for diseases, causes of death, and public health
practices [529];[530]. These regulations, unlike most international law, are binding on member states un-
less they proactively “opt out”. In addition, also the WHO enjoys several privileges and legal immunities.
Regardless of the original purpose of these privileges, the possibility of abuse of these privileges by the
WHO also exists. Also here the details were considered out of the scope of this review.
44
Private philanthropy, society and science
In his recent book, Callahan discussed the role of private philanthropy, noting the rising influence and
political significance of elite philanthropy, asking who is making choices over public life and who actually
benefits from those choices [531]. Callahan described “today’s era of austerity” as a result of an orche-
stration of the upper class to reduce its taxes and the size of government, even so that in some US states,
cuts to higher education specifically helped finance tax reductions for the wealthy and corporations. He
noted that in a decade, Bill Gates and Warren Buffett, the main funders of the Bill and Melinda Gates
Foundation, had added USD 25 billion and USD 80 billion, respectively, to their wealth, and that the
Koch brothers had increased their wealth from USD 9 billion in 2005 to USD 85 billion in 2015.
In a book review, Saunders-Hastings asked whether elite philanthropists are a counterweight to other,
self-interested elites or to democracy itself, and noted that the distance between elite “charity” and elite
political influence is small and shrinking, and that donors’ motivations matter less than the results of
their actions [532].
Broad wrote that due to cuts to public funding and increase in private donations, “American science,
long a source of national power and pride, is increasingly becoming a private enterprise” and quoted a
policy analyst commenting that “the practice of science in the 21st century is becoming shaped less by
national priorities or by peer-review groups and more by the particular preferences of individuals with
huge amounts of money” [533].
Callahan proposed putting some curbs in place against the private philanthropy, yet noted that foundati-
ons and nonprofit trade groups are strongly against any new restrictions, partly due to their dependency
on philanthropy. He noted that “rethinking philanthropic freedom is a Pandora’s box that almost nobody
wants to open”, saying the current situation was a result of “yesterday’s mantras about philanthropic
freedom and the dated regulation upholding it”.
Vaccines vs repurposed medicines
In Finland, a team led by two leading Finnish professors, Kari Alitalo and Seppo Ylä-Herttuala, had
a patent and intellectual property free adenovirus-based nasal spray COVID-19 vaccine ready in May
2020. Despite taking approximately EUR 18 billion of public debt to mitigate damages caused by societal
lockdowns and using hundreds of millions of Euros on diagnostic tests only, the Finnish government
refused the approximately EUR 50 million needed to fund a phase III patient trial for the vaccine [534];
[535].
The above case illustrates that the issue at hand is fundamentally not even about vaccines versus repur-
posed medicines or new pharmaceuticals versus repurposed medicines. Based on this data it is difficult
to say whether it is about excessive adherence to inflexible regulations, subconscious biases present in
corporate cultures and individuals, intellectual property enforcement, or intentional misleading for pro-
fit; likely, it is a mixture of all these factors. Personal biases, organizational cultures and commercial
incentives of the vaccine cluster may have lead to attempts to build near-monopolies mass-producing
proprietary but inferior products that outcompete more feasible alternatives. In Finland, significantly
less interest has been present for any repurposed medicine than for the patent-free vaccine, with the
sole exception of the company which developed the ivermectin-containing nasal spray not yet on the
market [356].
More generally, the situation may partly be a result of the unprepared and rushed way in which the
pandemic has been handled by the governments. Assumedly, from the perspective of governments with
95% of their funding committed to vaccines and international co-operation led by the WHO, paradigm
change inducing innovations from outsiders may be perceived as unwanted disturbances. Considering
these paradigms, the dismissal of ivermectin might be perceived as cultural discrimination, an instinctive
reaction to avoid unfamiliar ideas.
As a result of the chosen policy of vaccines and new pharmaceuticals only, in order to avoid losing the sunk
costs and credibility, the interests of the governments and the pharmaceutical industry appeared to align
with each other but likely not with the public health interest. The concept of “regulatory capture” may be
described as the agencies tasked with protecting the public interest coming to identify with the regulated
45
industry and protecting its interests against those of the public, with the result of government failing
to protect the public [536]. Whether rejection of ivermectin may be seen as an example of “regulatory
capture” depends on how the vaccines-only policy was selected: primarily to align with the interests of
the pharmaceutical industry, or because a better option could not be imagined. Curiously, options could
be imagined early on in many low-income countries, but not in the high-income countries, possibly as
a result of “technological capture”: when access to advanced technology exists, every problem looks like
a problem to be solved with advanced technology, even though such solutions would be suboptimal due
to being overly complex and unnecessarily expensive. For example, the idea of spending tens of billions
of dollars per year for testing 20 percent of the global population every week assumedly for a single
pathogen (SARS-CoV-2) appeared irrational at best [89]. Gates’s speeches repeated terms such as “war”
and “battle plan” [537]; these talks may easily be interpreted as priming fear in the public. Gates is also
famous for regularly predicting the next pandemics [538].
Since the beginning of 2021 at the latest it should have been obvious that the continuing denial of early
treatments could not be characterized either as accidental or as a rational choice with respect to public
health interest. During the pandemic, a large part of the medical community seemed incapacitated like an
old-fashioned military unit lacking leadership. The model based on the fear of losing medical license and
an inflexible hierarchical chain of command appeared unsuitable for ensuring proper care of populations.
While denial of treatments for certain illnesses such as drug addictions, post-traumatic stress disorder
or “treatment-resistant” depression for years or decades for example by denying funding for the research
of psychedelic therapies has become normalized, it was unexpected that in the case of COVID-19 this
antisocial behavior on behalf of governments and the pharmaceutical industry would be extended to
literally everyone in the world. In a comment suggesting adoption of ivermectin, a patent attorney and a
former director of a pharmaceutical company referred to “potential civil/criminal liability for censorship,
scientific misconduct for misrepresenting ivermectin and other generics” [387].
The exact causes of the situation remained unclear. Regardless, the consequences remain to be seen
and felt. One way forward might entail the majority of governments halting their funding to the WHO
in order to dissolve the whole organization which appeared beyond repair. Another necessary change
might be the eviction of the so-called philanthropic entities from healthcare contexts. In the long term,
another beneficial action might be a worldwide conversion of the pharmaceutical industry into a non-
profit operation. Continuing on the current path may result in a further polarization or destabilization
of societies.
Near-future objections to adoption of ivermectin will undoubtedly include the possible environmental
impacts. In the mid-to-long term, due to the need to reduce water usage and enable better retention of
nitrogen, phosphorus and ammonia [539], transition from water based sewer systems to toilet systems
not using water and not requiring wastewater processing but utilizing for example composting and new
kind of treatments to degrade pharmaceuticals will become inevitable in many areas in any case.
Conclusions
During this period, ivermectin was officially adopted in South Africa but not widely used, adopted
but later dropped in most of India, and adopted in Indonesia. In the United States and the United
Kingdom, projects with involvement of both the governments and commercial companies were announced
for development of new pharmaceuticals for early outpatient treatment of COVID-19, indicating unclear
boundaries between these entities. The dismissal of repurposed medicines including ivermectin continued
in high-income countries due to very differing views on what constituted evidence of efficacy. The divide
between ivermectin proponents and opposers remained mostly unchanged during the period, indicating
a stagnated situation.
There was a noticeable centralization of power, with pandemic response and public discussions largely
directed by a few organizations that were largely funded by a few billionaires which, in turn, were affected
by their own personal preferences and biases such as obsessive-compulsive attachment to testing and new
technologies, primarily vaccines. Legal responsibilities of these organizations appeared, in the words of
one researcher, “obscure”.
46
Commercial interests appeared to override public health interests during this period. As a result, se-
veral low-and-middle-income countries and regions either implicitly or explicitly disregarded the WHO
guidance, accelerating an erosion of WHO’s credibility.
Abbreviations
SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: coronavirus disease 2019;
WHO: World Health Organization; C-TAP: WHO’s Covid-19 Technology Access Pool; ACT-Accelerator:
Access to COVID-19 Tools Accelerator under WHO; COVAX: COVID-19 Vaccines Global Access, a vac-
cine arm of ACT-Accelerator; PAHO: Pan American Health Organization; NIH: United States National
Institutes of Health; NIAID: National Institute of Allergy and Infectious Diseases; CDC: United States
Centers for Disease Control and Prevention; FDA: United States Food and Drug Administration Agency;
EMA: European Medicine Agency; CADTH: Canadian Agency for Drugs and Technologies in Health;
SAHPRA: South African Health Products Regulatory Authority; ICMR: Indian Council of Medical Re-
search; CEPI: Coalition for Epidemic Preparedness Innovations; Gavi: Global Alliance for Vaccines and
Immunization, or Gavi The Vaccine Alliance; IFPMA: International Federation of Pharmaceutical Manu-
facturers and Associations; TNI: Trusted News Initiative; IFCN: International Fact-Checking Network;
JAMA: Journal of American Medical Association; BMJ: British Medical Journal; LMIC: low-or-middle-
income country; CSU: Christian Social Union in Bavaria; NGO: non-governmental organization; BIRD:
British Ivermectin Recommendation Development Group; FLCCC: Frontline COVID-19 Critical Care
Alliance; ICU: intensive care unit; RCT: randomized controlled trial; MEDLINE: Medical Literature Ana-
lysis and Retrieval System Online; PubMed: a search engine for the MEDLINE database; NCT: number
of clinical trial, a ClinicalTrials.gov identifier; LHCS: long haul COVID-19 syndrome; HCQ: hydroxychlo-
roquine; IVM: ivermectin; mRNA: messenger ribonucleic acid; D-Dimer: a fibrin degradation product;
PCR: polymerase chain reaction; IC50: half maximal inhibitory concentration; CFR: case fatality ratio;
EUA: Emergency Use Authorization; CD147: Basigin (BSG), or extracellular matrix metalloproteinase
inducer (EMMPRIN), or cluster of differentiation 147; RdRp: RNA-dependent RNA polymerase; RR:
relative risk, or risk ratio; CI: confidence interval; OR: odds ratio; r: correlation coefficient; p: p-value.
Acknowledgements
The author wishes to thank Simon Barber for a grammar check.
Authors’ contributions
The author was responsible for all aspects of the manuscript.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors.
Availability of data and materials
Not applicable.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The author declares that he has no competing interests.
Author details
Independent researcher, Helsinki, Finland. ORCID iD: 0000-0002-8575-9838
47
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