Ivermectin for Covid-19
Amelia Carolina Sparavigna
sursa:
https://www.researchgate.net/publication/342170742_Ivermectin_for_Covid-19
Department of Applied Science and Technology, Politecnico di Torino
Discussion of scholarly papers published on Ivermectin, starting from the article of Caly et al. in
Antiviral Research, available online April 3, 2020, and of some news that we can find about the use
of this drug for the treatment of Covid-19. A list of clinical trials is also given. The proposed
discussion was made in a series of versions from 14 June this of 29 July 2020. For what concerns
scholarly papers, we report among them two preprints in MedRχiv. One, posted on 10 June,
concludes that Ivermectin was associated with lower mortality during treatment of Covid-19. The
other preprint, posted on 8 July, is showing the result of a clinical trial. This preprint tells, in its
conclusions that add-on use of Ivermectin is giving better results when compared to controls, in
particular a significant shorter hospitalization. A preprint, posted in Research Square on July 14, is
reported too. This preprint is giving the result of a trial regarding the combinations Ivermectin-
Doxycycline and Hydroxychloroquine-Azithromycin. Among news, we consider especially the
news regarding the use of Ivermectin in Peru. The case of Iquitos is discussed in detail. In Iquitos,
capital of the Department of Loreto, by May 25 Covid-19 cases and deaths had dropped notably, as
reported on the web. Epidemic data in this region are considered. Recent news (July 27), displaying
the observation of rare symptoms of Covid-19, is also reported in detail. The observation was
related to a set of more than 3,000 patients in Lima. The formulation of Ivermectin used in Peru is
also discussed, in particular that of the oral solution, disclosed by the Peruvian Government.
Torino, First version 14 June 2020 - Last version July 29, 2020 - DOI 10.5281/zenodo.3893750
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1 - Introduction
2 - The drug and the Nobel Prize
3 - The trailblazer of the use of Ivermectin against onchocerciasis
4 - a) Scholarly Papers, b) ChemRχiv, c) MedRxiv, d) Research Square preprints
5 - Clinical trials regarding the use of Ivermectin for Covid-19
6 - News from Bangladesh, Italy, US and Israel
7 - The problem of Surgisphere
8 - News from Peru and Bolivia
9 - The case of Iquitos (Peru)
10 - A drug for humans
11 - Stabilized aqueous formulation
12 - "There are no parenteral antihelminthic drugs licensed for use in humans"
13 - News propagation
14 - Discussion in TrialSite - A Health Movement
15 - Further news until 20 July and a report from Dr. T. Alam
16 - Not all doctors
17 - US monopolises Remdesivir
18 - From Bulgary, India and Brazil
19 - a) SSRN or Antiviral Research, b) Un breve commento sul documento in SSRN, ora ritirato
20 - Rare symptoms of Covid-19 - a report from Dr. E. Durand, Lima
21 - Making ivermectin for oral use (6mg/mL)
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22 - Data
Acknowledgement - Appendix - References
__________________
Before reading this work, please consider that I am not a physician. I do not suggest the use of
ivermectin. I am not touting this drug. As previously told, the analysis of publications and news
about ivermectin is made in the framework of a wider investigation about information concerning
drugs used for Covid-19.
_________________
1 - Introduction - In [SPA1], an article which is discussing the drugs used in Italy for the treatment
of Covid-19, we mentioned Ivermectin. In [SPA1], published on 9 May 2020, we reported the news
"Novità positive su Remdesivir e altri farmaci COVID-19/Farmaci", dated 7 May and written by
Ernesto Carafoli and Enrico Bucci, archived http://archive.is/YdIqh . It is told that "L’ultimo
farmaco giunto sulla scena del Covid-19 che vale la pena di citare è l’Ivermectina: un
antiparassitario noto per la sua attività antivirale a largo spettro usato anche in terapia umana per
affezioni dermatologiche. Un interessante studio australiano ha dimostrato che la sua aggiunta a
cellule infettate con SARS_CoV-2 riduce in 48 ore il livello dell’RNA infettante di 5000 volte.
Tuttavia, bisogna considerare alcune obiezioni che sono state sollevate, prima di essere sicuri che
abbia senso iniziare dei trial su questo composto, come peraltro sembra si voglia fare in Francia".
That is, the latest drug that arrived on Covid-19 scene, and which is worth mentioning, is
Ivermectin. This drug is a pesticide known for its broad-spectrum antiviral activity and also used in
human therapy for dermatological diseases. An interesting Australian study has shown that its
addition to SARS_CoV-2 infected cells reduces the level of infectious RNA in 48 hours by 5000
times. However, it is necessary to consider some objections that have been raised, before being sure
that it makes sense to start trials on this compound, as it seems to be done in France.
Let us see the scholarly papers published until July 2020, on Ivermectin and some news, that we
can find about its use for Covid-19. For what concerns scholarly papers, among them we can find
two preprints in MedRχiv. One, posted on 10 June, concludes that Ivermectin was associated with
lower mortality during treatment of Covid-19. The other preprint, posted on 8 July, is showing the
result of a clinical trial. This preprint tells, in its conclusions that add-on use of Ivermectin is giving
better results when compared to controls, in particular a significant shorter hospitalization. A further
preprint, posted in Research Square on July 14, is available too. This preprint is giving the result of
a trial regarding the combinations Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin.
Among news, we consider especially the news regarding the use of Ivermectin in Peru. The case of
Iquitos is discussed in detail. In Iquitos, capital city of the Department of Loreto, by May 25 Covid-
19 cases and deaths had dropped notably, as reported on the web. Epidemic data in this region are
considered. Recent news (July 27), displaying the observation of rare symptoms of Covid-19, is
also reported in detail. The observation was related to a set of more than 3,000 patients in Lima.
The aim of the discussion is to understand the different approach to Covid-19 treatment, based on
ivermectin, which is evident in Peru. In fact, the following discussion is made in the framework of
an investigation, which started from drugs used in Italy [SPA1-SPA9]. For what concerns the news,
in some cases, it has been preferred to left the original excerpt, to avoid misunderstanding.
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2 - The Drug and the Nobel Prize - Before discussing literature and news relevant for the use of
Ivermectin in Covid-19, let us remember the extraordinary history of the drug. Ivermectin is a drug
derived from avermectin. Actually, the term "avermectin" represents a series of drugs and pesticides
used to treat parasitic worms and insect pests. Its molecules are naturally occurring, being generated
as fermentation products by Streptomyces avermitilis, a soil actinomycete. Half of the 2015 Nobel
Prize in Physiology or Medicine was awarded to William C. Campbell and Satoshi Ōmura, for
discovering avermectin, the derivatives of which have drastically lowered the incidence of river
blindness and lymphatic filariasis. The other half of the prize was awarded to Tu Youyou for her
discoveries concerning a novel therapy against Malaria. http://archive.is/JMRhi
About ivermectin, here what is told by WHO: "The treatment for onchocerciasis is ivermectin
(brand name Mectizan®). Unlike previous treatments, which had serious – sometimes fatal – side
effects, ivermectin is safe and can be used on a wide scale. It is also a very effective treatment, and
has single-handedly transformed the lives of millions of people suffering from onchocerciasis since
its introduction in 1987". https://www.who.int/apoc/cdti/ivermectin/en/ archived http://archive.is/FizVA .
3 - The trailblazer of the use of Ivermectin against onchocerciasis
In fact, Ivermectin was the new drug that "led to a revolutionary break-through in the late 1980s for
human onchocerciasis control" [CUP1]. At the beginning of that decade, the ivermectin was
observed as being "efficacious against the microfilariae of Onchocerca cervicalis, a common
parasite of horses. Of particular interest was that none of the ivermectin-treated animals exhibited
the gross or clinical reactions commonly associated with diethylcarbamazine treatment (Klei et al.,
1980). Using that finding, Aziz et al. (1982) [AZI1] conducted a preliminary clinical trial of 32
patients in Senegal infected with O. volvulus and found the drug to be efficacious and safe. This
seminal report led to a series of in-depth studies in Africa spanning 4–6 years aimed at determining
dosage efficacy, tolerance and possible effects on parasite transmission" [CUP1]. Among the main
results of these studies we find that ivermectin is highly tolerated and "therefore can be used in
mass drug administration programs". "Controlled clinical studies have indicated that a single oral
dose of ivermectin is safer and more effective therapy for onchocerciasis than the standard seven- to
10-day course of diethylcarbamazine" [AZI2]. As explained in [AZI3], the other drugs used against
onchocerchiasis have serious side effects, but ivermectin was highly tolerated.
The "trialblazer" of the use of Ivermectin against onchocerciasis was Mohammed Abdul Aziz. " In
1981-1982, Dr. Mohammed Aziz at MDRL, an expert in River Blindness, conducted the first
successful human trial (Aziz et al., 1982) [AZI1]. The results were clear - patients given a single
dose of Ivermectin showed either complete elimination or near elimination of microfilariaload,
while the adult parasites were untouched" [NPM1]. The success of Ivermectin in clinical trials had
the following result. In 1982, Merck, the producer of Mectizan®, and WHO began a research
program, the Mectizan Donation Program, under the guidance of Mohammed Aziz and Kenneth
Brown, director of Merck's development of ivermectin for human use.
In 2015, "A Trailblazer in Medicine", written by Leedy Hoque, https://www.thedailystar.net/op-
ed/trailblazer-medicine-179983 , gave a movingly memory of Dr. Aziz, Leedy's father.
4 -a - Scholarly Papers
Here we consider the papers on ivermectin in relation to Covid-19. In the above-mentioned article
written by Carafoli and Bucci, it is told of an interesting Australian study concerning the drug. This
study is published in [CAL1] (available from Apr 3, 2020).
Ref. [CAL1] is the origin of researches, trials and use of Ivermectin for Covid-19. The authors -
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Caly, L., Druce, J., Catton, M., Jans, D. & Wagstaff, K. - tell that this drug, an FDA-approved anti-
parasitic, which has previously shown to have broad-spectrum anti-viral activity in vitro, "is an
inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h
post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h.
Ivermectin therefore warrants further investigation for possible benefits in humans". The
authors are also telling that, "Ultimately, development of an effective anti-viral for SARS-CoV-2, if
given to patients early in infection, could help to limit the viral load, prevent severe disease
progression and limit person-person transmission".
"The paper by Caly et al. has also elicited two letters to the editor," (Mike Bray, MD, Editor-in-
chief) The letters are printed in [BRA1], followed by the authors' response to both letters. [BRA1]
was published online 2020 Apr 21. "Readers should be aware that neither the letters nor the
response has been peer-reviewed, so appropriate caution should be used in quoting or citing them".
Some objections concerning the use of Ivermectin for Covid-19 exist. We can find them given in
[SCH1]. In the abstract it is told that "Caly, Druce [CAL1] reported that ivermectin inhibited
SARS-CoV-2 in vitro for up to 48 h using ivermectin at 5 uM. The concentration resulting in 50%
inhibition (IC50, 2 uM) was >35x higher than the maximum plasma concentration (Cmax) after oral
administration of the approved dose of ivermectin when given fasted". Authors of [SCH1] conclude
that "The likelihood of a successful clinical trial using the approved dose of ivermectin is low.
Combination therapy should be evaluated in vitro. Re-purposing drugs for use in COVID-19
treatment is an ideal strategy but is only feasible when product safety has been established and
experiments of re-purposed drugs are conducted at clinically relevant concentrations".
In [CHO1], it is told that "potential drugs like hydroxychloroquine, ivermectin and azithromycin
have been tested by diverse group of researchers worldwide for their potential against novel
coronavirus". The authors of [CHO1] are proposing a report derived from the major researches
about the above-mentioned drugs. "Hydroxychloroquine and ivermectin were known to act by
creating the acidic environment and inhibiting the importin (IMPα/β1) mediated viral import.
Azithromycin was found to act similar to the hydroxychloroquine as an acidotropic lipophilic weak
base. All the three categories of drugs seemed to potentially act against novel coronavirus infection.
However, their efficacies need to be studied in detail individually and in combination in-vivo in
order to combat COVID-19 infection".
Ref. [CHO1] illustrates the action of Ivermectin, as we can also find in Ref. [CAL1]. "SARS-CoV-2
(causative agent of COVID-19) is a single stranded RNA virus (positive sense) which is closely
related to SARS coronavirus (SARS-CoV). Recent study on ivermectin against SARS-CoV-2 under
in vitro conditions revealed that it can inhibit the viral replication. The single treatment of this drug
was able to reduce the virus up to 5000-fold in culture within 48h. However, no further reduction
was reported with further increase in time period i.e up to 72h. Moreover, no toxicity was seen with
the drug at any point of time" [CAL1]. "Mechanism by which ivermectin responded against the
CoV-19 virus is not known and was believed to be working similarly as it acted on other viruses. It
was known to inhibit the nuclear import of viral and host proteins. Integrase protein of viruses and
the importin (IMP) α/β1 heterodimer was responsible for IN nuclear import which further increases
the infection. As most of the RNA viruses are dependent upon IMPα/β1 during infection,
Ivermectin acts on it and inhibits the import with the increase in antiviral response" [CAL1],
[JAN1].
In Ref. [SHA1] the authors report, as [CAL1] and [CHO1], that the "antiviral potential of
ivermectin against various viruses is mediated via the targeting of the following: importin α/β-
mediated nuclear transport of HIV-1 integrase and NS5 polymerase; NS3 helicase; nuclear import
of UL42; and nuclear localization signal-mediated nuclear import of Cap. As SARS-CoV-2 is an
RNA virus, the antiviral activity of ivermectin may be mediated through the inhibition of importin
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α/β-mediated nuclear transport of viral proteins. The clinical efficacy and utility of ivermectin in
SARS-CoV-2-infected patients are unpredictable at this stage, as we are dealing with a completely
novel virus".
In [SHA1], it is told that it "has also been hypothesized that combination therapy using
hydroxychloroquine and ivermectin may exert a synergistic inhibitory effect on SARS-CoV-2. In
this combination, hydroxychloroquine acts by inhibiting the entry of SARS-CoV-2 into the host
cells, whereas ivermectin further enhances the antiviral activity by inhibiting viral replication"
[PAT1].
In [RIZ1], we find an article proposing "an alternative mechanism of action for this drug
[Ivermectin] that makes it capable of having an antiviral action, also against the novel coronavirus,
in addition to the processes already reported in literature".
In [CHA1], the dosage of Ivermectin is considered. "Caly et al. report a 5,000-fold reduction in
SARS-CoV-2 RNA levels, compared with those in controls, after infected Vero/hSLAM cells were
incubated for 48 hours with 5 μM ivermectin. ... Pharmacokinetic studies in healthy volunteers have
suggested that single doses up to 120 mg of ivermectin can be safe and well tolerated. However,
even with this dose," which is quite greater than those approved by the US FDA we are "one order
of magnitude lower than effective in vitro concentrations against SARS-CoV-2. These findings may
seem to discourage follow-up clinical trials with ivermectin. However, some in vivo effect may be
possible even if efficacious in vitro concentrations are physiologically unattainable. ... Until we
have a better understanding of ivermectin’s antiviral mode of action and of appropriate in vitro
systems for testing, we caution against using findings in Vero cells as more than a qualitative
indicator of potential efficacy". The authors continue telling that they "believe the recent findings
regarding ivermectin warrant rapidly implemented controlled clinical trials to assess its efficacy
against SARS-CoV-2. These trials may open a new field of research on the potential use of
avermectin antiparasitic drugs, including compounds with an improved pharmacokinetic profile, as
antivirals". The authors are pointing out some points, that need to be considered "before testing
ivermectin in severe disease". Three of the authors of [CHA1] are involved in trial [CHA2].
In [HEI1], abstract tells that "Ivermectin plays a role in several biological mechanisms, therefore it
could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19
as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal
models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are
necessary to appraise the potential efficacy of ivermectin in clinical setting". Ref. [HEI1] is a
systematic review of the antiviral effects of Ivermectin. "Several studies reported antiviral effects of
ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, ... Furthermore, there
are some studies showing antiviral effects of ivermectin against DNA viruses". Playing a role in
several biological mechanisms, Ivermectin "could serve as a potential candidate in the treatment of
a wide range of viruses including COVID-19 as well as other types of positive-sense single-
stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects
of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin
in clinical setting".
In [ARU1], we find told that "There are many common observations between COVID-19 and
dengue. Elevated levels of ferritin, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF),
D-dimer, coagulopathy, urticaria and ARDS are reported in both diseases. There are many
indicators that mast cell degranulation and histamine release may have a major role in COVID-19
and dengue severity. Mast cell stabilizers, antihistamines, Vitamin C, HCQ, azithromycin,
ivermectin may address different aspects of this cascade and thus reduce disease severity. Disease
mechanisms and immunopathology must be understood. Focusing on anti-viral action of drugs
alone could be counter productive. For example, CQ had no effect on viraemia but decreased cases
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of DHF".
"The in vitro antiviral activity end-points are analyzed from the pharmacokinetic perspective. The
available pharmacokinetic data from clinically relevant and excessive dosing studies indicate that
the SARS-CoV-2 inhibitory concentrations are not likely to be attainable in humans". This is told in
Ref. [MOM1].
In [ACH1], it is told that "Concerning the treatment outcome, adverse effect, and safety, Ivermectin
- Doxycycline combination is a better alternative to Hydroxychloroquine - Azithromycin therapy in
the case of mild to moderate degree of COVID19 patients. Though, both the treatment regimens
were found to be effective in this study" (On July 14, 2020, the same group of researchers [ACH1]
posted in Research Square the results of their clinical trial [ACH2]).
According to [GON1], the results are the following. "The search of the databases led to the retrieval
of 25 articles. After the different phases of the selection process, eight articles were included in the
present review for the extraction of relevant data. The results suggest that ivermectin inhibits the
viral replication of SARS-CoV-2 through the action of the hypoxia-inducible factor (HIF-1α) and
consequent destabilization of importin α/β1 proteins. Conclusions tell that "Ivermectin inhibits the
viral replication of SARS-CoV-2. Laboratory and clinical studies are needed to provide more
evidence in terms of the best posology and possible associations with other drugs for combatting
COVID-19".
In [PAN1], authors tell that "Ivermectin acts by selectively binding to the glutamate-gated chloride
on channels of the parasite and leads to hyperpolarization of the cell which results in the paralysis
and death of the parasite". The anti-viral activity of ivermectin was first discovered with its ability
to block the interaction between the nuclear transport receptor importin α/β(IMP) and integrase
molecule of HIV. It is also known to block the viral replication of host of viruses including
influenza, flavivirus and dengue virus. ... A phase-III, double blind, randomized clinical trial has
been started with the aim to determine the safety and efficacy profile of the combination therapy of
hydroxychloroquine and ivermectin I the treatment of hospitalized COVD-19 patients" (see the
Clinical Trial https://clinicaltrials.gov/ct2/show/NCT04391127).
In [GUP1], we find a Letter to the Editor of The Brazilian Journal of Infectious Diseases, entitled
"Ivermectin: potential candidate for the treatment of Covid 19". And a question is posed in [ECH1]:
Ivermectina: ¿La respuesta de Latinoamérica frente al SARS-CoV-2?
Ref. [MOL1] contains a discussion which is necessary to read, in particular because of the news that
we will see in the following. A "word of caution is more than required and opportune specially for
the use of IVM [ivermectin]. Although available data are coming from front-line medical personnel,
and official sources, most of the evidences are based on entirely empirical facts".
In Ref. [WIJ1], the authors are reporting "three confirmed cases of COVID-19 infection with
significant improvement clinically and radiologically following treatment with single dose of
ivermectin".
In [KUM1], a review is proposed, published 6 July. The abstract tells that "documentations serve as
a ray of hope for considering ivermectin in treating COVID-19 due to its suggested nuclear
transport inhibitory mechanism".
Other working papers (see Refs. [SCD1], [SCD2], [AGU1], [ORT1], [SHW1], [SOT1]) are given
in SSRN and Researchgate.
For what concerns Ivermectin in general, I strongly suggest the reading of articles [CRU1],
[CAM1], [ACS1]. Let us add also [BUO1]. The Background of the article is the following:
"Strongyloides stercoralis infection is a neglected condition that places people who are
immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the
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treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial
aimed to assess whether multiple doses of ivermectin were superior to a single dose for the
treatment of non-disseminated strongyloidiasis". Then, this article is important for what concerns
adverse effects of the drug. Authors tell that "Adverse events were generally of mild intensity and
more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due
to futility". Interpretation: "Multiple doses of ivermectin did not show higher efficacy and was
tolerated less than a single dose. A single dose should therefore be preferred for the treatment of
non-disseminated strongyloidiasis".
Then, as we have seen, WHO tells that ivermectin is "safe and can be used on a wide scale", and
adverse effects are "generally of mild intensity and more frequent in the multiple-dose".
From now on (that is, July 28, 2020), only scholarly articles with specific results and reporting on
the treatment of Covid-19 patients, will be added.
4 - b - ChemRχiv preprints
Let us consider two preprints in ChemRχiv. In [SEN1], 12 different COVID-19 targets are studied.
Among them, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site
show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively.
"Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of
RdRp with RNA has better structural stability than the Helicase NCB site, with MM/PBSA free
energy of -135.2 kJ/mol, almost twice that of Helicase (-76.6 kJ/mol). The selectivity of Ivermectin
to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation.
Identification of the target and its interaction profile with Ivermectin can lead to more powerful
drug designs for COVID-19 and experimental exploration".
Ref. [MAU1] is the other ChemRχiv preprint. It is discussing the combination Ivermectin and
Doxycycline. As we will see from news, "in Bangladesh, a group of doctors reported astounding
success in treating patients suffering from COVID-19 with two commonly used drugs, Ivermectin
and Doxycycline". In [MAU1], the author explored the possible mechanism by which the drugs
"might have worked for the positive response in the COVID-19 patients". To explore the
mechanism, molecular docking and the molecular dynamics simulations have been used. The study
"shows that both Ivermectin and doxycycline have significantly bind with SARS-CoV-2 proteins
but Ivermectin was better binding than doxycycline. Ivermectin showed a perfect binding site to the
Spike-RBD and ACE2 interacting region indicating that it might be interfering in the interaction of
spike with ACE2 and preventing the viral entry in to the host cells. Ivermectin also exhibited
significant binding affinity with different SARS-CoV-2 structural and non-structural proteins
(NSPs) which have diverse functions in virus life cycle. ... Thus, our docking and simulation studies
reveal that combination of Ivermectin and doxycycline might be executing the effect by inhibition
of viral entry and enhance viral load clearance by targeting various viral functional proteins".
4 - c - MedRχiv preprints
Let us conclude the review of scholarly articles on the use of Ivermectin in Covid-19 patients with
two preprint in MedRχiv.
In [RAJ1], the authors conclude that "Ivermectin was associated with lower mortality during
treatment of COVID-19, especially in patients who required higher inspired oxygen or ventilatory
support. These findings should be further evaluated with randomized controlled trials". Objective of
[RAJ1]: "To determine whether Ivermectin is associated with lower mortality rate in patients
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hospitalized with COVID-19". Design and Setting are: "Retrospective cohort study of consecutive
patients hospitalized at four Broward Health hospitals in South Florida with confirmed SARS-CoV-
2. Enrollment dates were March 15, 2020 through May 11, 2020. Follow up data for all outcomes
was May 19, 2020. Participants: 280 patients with confirmed SARS-CoV-2 infection (mean age
59.6 years [standard deviation 17.9], 45.4% female), of whom 173 were treated with ivermectin and
107 were usual care were reviewed".
In [GOR1], the results of the clinical trial NCT04343092C have been proposed (see the next section
for all the clinical trials available at ClinicalTrials.gov). The preprint was posted on July 08, 2020.
Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial), by Faiq I.
Gorial et al. , preprint in MedRχiv.
From the Abstract. In vitro, studies indicated that ivermectin (IVM) has antiviral effect. The
researchers made the clinical trial to assess the effectiveness of ivermectin (IVM) as add-on therapy
to hydroxychloroquine (HCQ) and azithromycin (AZT) in treatment of COVID-19. "Methods: This
Pilot clinical trial conducted on hospitalized adult patients with mild to moderate COVID-19
diagnosed according to WHO interim guidance. Sixteen Patients received a single dose of IVM
200Mcg /kg on admission day as add on therapy to hydroxychloroquine (HCQ) and Azithromycin
(AZT) and were compared with 71 controls received HCQ and AZT matched in age, gender,
clinical features, and comorbidities. The primary outcome was percentage of cured patients, defined
as symptoms free to be discharged from the hospital and 2 consecutive negative PCR test from
nasopharyngeal swabs at least 24 hours apart. The secondary outcomes were time to cure in both
groups and evaluated by measuring time from admission of the patient to the hospital till discharge.
Results: Of 87 patients included in the study, the mean age ± SD (range) of patients in the IVM
group was similar to controls ... Majority of patients in both groups were male but statistically not
significant ... All the patients of IVM group were cured compared with the controls [ 16 (100 %) vs
69 (97.2 %)]. Two patients died in the controls. The mean time to stay in the hospital was
significantly lower in IVM group compared with the controls (7.62 ±2.75 versus 13.22 ±.90 days,
p=0.00005, effect size= 0.82). No adverse events were observed Conclusions : Add-on use of IVM
to HCQ and AZT had better effectiveness, shorter hospital stay, and relatively safe compared with
controls. however, a larger prospective study with longer follow up may be needed to validate these
results".
4 - d - Research Square preprints
On July 14, 2020, the same authors of [ACH1] posted in Research Square the results of their
clinical trial [ACH2]. In their study, the authors "investigated and compared outcomes of
Ivermectin-Doxycycline vs. Hydroxychloroquine-Azithromycin combination therapy COVID19
patients with mild to moderate disease". Patients with mild to moderate COVID-19 disease were
tested positive by RT PCR for SARS-CoV-2 infection. "Patients were divided randomly into two
groups: Ivermectin 200μgm/kg single dose + Doxycycline 100 mg BID for 10days in group A, and
Hydroxychloroquine 400 mg 1st day, then200mg BID for 9days + Azithromycin 500 mg daily for 5
days in group B". "All subjects in the Ivermectin-Doxycycline group (group A) reached a negative
PCR for SARS-CoV-2, at a mean of 8.93 days, and all reached symptomatic recovery, at a mean of
5.93 days, with 55.10% symptom-free by the 5th day. In the Hydroxychloroquine-Azithromcyin
group (group B), 96.36% reached a negative PCR at a mean of 6.99 days and were symptoms-free
at 9.33 days. Group A patients had symptoms that could have been caused by the medication in
31.67% of patients, including lethargy in 14(23.3%), nausea in 11(18.3%), and occasional vertigo in
7(11.66%) of patients. In Group B, 46.43% had symptoms that could have been caused by the
medication, including 13(23.21%) mild blurring of vision and headache; 22(39.2%) increased
lethargy and dizziness, 10(17.85%) occasional palpitation, and 9(16.07%) nausea and vomiting".
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According to the researchers, "Ivermectin-Doxycycline combination showed a trend toward
superiority to the Hydroxychloroquine-Azithromycin combination therapy in the case of patients
with mild to moderate COVID19 disease, though the difference in time to becoming symptom-free
and the difference in time to negative PCR was not statistically significant".
5 - Clinical trials regarding the use of Ivermectin for Covid-19
On July 28, 2020, we can find 33 clinical trials reported by ClinicalTrials.gov , at the following link
https://clinicaltrials.gov/ct2/results?cond=COVID&term=ivermectin+&cntry=&state=&city=&dist=
For other trials about drugs for Covid-19, see [SPA4].
In the following list, the date is that when the trial was first posted on ClinicalTrials.gov .
1) 13 April 2020 - Efficacy of Ivermectin as Add on Therapy in COVID19 Patients - Drug:
Ivermectin (IVM) - Locations: General Directorate of Medical City, Bagdad, Baghdad, Iraq -
https://ClinicalTrials.gov/show/NCT04343092
2) 4 May 2020 - Max Ivermectin - COVID 19 Study Versus Standard of Care Treatment for
COVID 19 Cases. A Pilot Study - Drug: Ivermectin - Locations: Max Super Speciality
hospital, Saket (A unit of Devki Devi Foundation), New Delhi, Delhi, India -
https://ClinicalTrials.gov/show/NCT04373824
3) 19 May 2020 - Efficacy of Ivermectin in COVID-19 - Drug: Ivermectin 6 MG Oral
Tablet (2 tablets) - Locations: Combined Military Hospital Lahore, Lahore, Punjab, Pakistan
- https://ClinicalTrials.gov/show/NCT04392713
4) 27 May 2020 - Ivermectin and Doxycycine in COVID-19 Treatment - Drug: Ivermectin,
Doxycycline, Chloroquine - Locations: Sherief Abd-Elsalam, Tanta, Egypt -
https://ClinicalTrials.gov/show/NCT04403555
5) 9 June 2020 - Prophylactic Ivermectin in COVID-19 Contacts - Drug: Ivermectin Tablets -
Locations: Zagazig University, Zagazig, Sharkia, Egypt -
https://ClinicalTrials.gov/show/NCT04422561
6) 11 June 2020 - Ivermectin In Treatment of COVID 19 Patients - Drug: Ivermectin -
Locations: isolation and referal hospitals for COVID 19 patients, Cairo, Egypt -
https://ClinicalTrials.gov/show/NCT04425707
7) 17 April 2020 - The Efficacy of Ivermectin and Nitazoxanide in COVID-19 Treatment -
Drug: Chloroquine, Nitazoxanide, Ivermectin - Locations: Tanta University, Tanta, Egypt -
https://ClinicalTrials.gov/show/NCT04351347
8) 22 May 2020 - Ivermectin-Azithromycin-Cholecalciferol (IvAzCol) Combination Therapy
for COVID-19 - Drug: Ivermectin, Azithromycin, Cholecalciferol - Locations: Outpatient
treatment, Mexico City, Mexico - https://ClinicalTrials.gov/show/NCT04399746
9) 11 May 2020 - Ivermectin Effect on SARS-CoV-2 Replication in Patients With COVID-
19 - Drug: IVERMECTIN (IVER P®) arm will receive IVM 600 μg / kg once daily plus
standard care. CONTROL arm will receive standard care. - Locations: Centro de Educación
Médica e Investigaciones Clínicas "Norberto Quirno" CEMIC, Buenos Aires, Ciudad De
Buenos Aires, Argentina - https://ClinicalTrials.gov/show/NCT04381884
10) 5 May 2020 - Trial to Promote Recovery From COVID-19 With Ivermectin or
Endocrine Therapy - Drug: Bicalutamide 150 Mg Oral Tablet|Drug: Ivermectin 3Mg Tab -
Locations: Johns Hopkins Hospital, Baltimore, Maryland, United States -
https://ClinicalTrials.gov/show/NCT04374279
9
11) 24 April 2020 - Ivermectin and Nitazoxanide Combination Therapy for COVID-19 -
Combination Product: Ivermectin plus Nitazoxanide, Other: Standard Care -
https://ClinicalTrials.gov/show/NCT04360356
12) 18 May 2020 - New Antiviral Drugs for Treatment of COVID-19 - Drug: Treatment
group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of
seven days - Locations: Mansoura University, Mansoura, Select A State Or Province, Egypt
- https://ClinicalTrials.gov/show/NCT04392427
13) 16 June 2020 - A Comparative Study on Ivermectin and Hydroxychloroquine on the
COVID19 Patients in Bangladesh - Drug: Ivermectin + Doxycycline | Drug:
Hydroxychloroquine + Azithromycin - Locations: Chakoria Upazilla Health Complex,
Cox's Bazar, Bangladesh - https://ClinicalTrials.gov/show/NCT04434144
14) 12 June 2020 - Ivermectin vs. Placebo for the Treatment of Patients With Mild to
Moderate COVID-19 - Drug: Ivermectin Oral Product - Locations: Sheba Medical
Center, Ramat-Gan, Israel - https://ClinicalTrials.gov/show/NCT04429711
15) 18 May 2020 - Hydroxychloroquine and Ivermectin for the Treatment of COVID-19
Infection - Drug: Hydroxychloroquine, Ivermectin, Placebo - Locations: Jose Manuel
Arreola Guerra, Aguascalientes, Mexico - https://ClinicalTrials.gov/show/NCT04391127
16) 28 May 2020 - Efficacy of Ivermectin in Adult Patients With Early Stages of COVID-19
- Drug: Ivermectin Oral Product, Placebo - https://ClinicalTrials.gov/show/NCT04405843
17) 29 May 2020 - Efficacy and Safety of Ivermectin and Doxycycline in Combination or
IVE Alone in Patients With COVID-19 Infection. - Drug: Ivermectin + Doxycycline +
Placebo, Ivermectin + Placebo, Placebo - https://ClinicalTrials.gov/show/NCT04407130
18) 15 May 2020 - Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal Trial - Drug:
Ivermectin, Placebo - Clinica Universidad de Navarra, Pamplona, Navarra, Spain -
https://ClinicalTrials.gov/show/NCT04390022
19) 17 June 2020 - Ivermectin vs Combined Hydroxychloroquine and Antiretroviral Drugs
(ART) Among Asymptomatic COVID-19 - Drug: Ivermectin Pill, Combined
ART/hydroxychloroquine - Locations: Siriraj Hospital, Bangkok Noi, Bangkok, Thailand -
https://ClinicalTrials.gov/show/NCT04435587
20) 29 May 2020 - Efficacy, Safety and Tolerability of Ivermectin in Subjects Infected With
SARS-CoV-2 With or Without Symptoms - Drug: Ivermectin, Placebo -
https://ClinicalTrials.gov/show/NCT04407507
21) 11 May 2020 - Novel Regimens in COVID-19 Treatment - Drug: Nitazoxanide,
Ivermectin, Chloroquine, Azithromycin - https://ClinicalTrials.gov/show/NCT04382846
22) 11 June 2020 - IVERMECTIN Aspirin Dexametasone and Enoxaparin as Treatment of
Covid 19 - Drug: Ivermectin 5 MG/ML - Locations: Hospital Eurnekian, Buenos Aires,
Argentina - https://ClinicalTrials.gov/show/NCT04425863
23) 11 June 2020 - USEFULNESS of Topic Ivermectin and Carrageenan to Prevent
Contagion of Covid 19 - Device: iota carrageenan, Ivermectin - Locations: Hospital
Eurnekian, Buenos Aires, Argentina - https://ClinicalTrials.gov/show/NCT04425850
24) 5 May 2020 - Novel Agents for Treatment of High-risk COVID-19 Positive Patients -
Drugs: Hydroxychloroquine|, Hydroxychloroquine and Azithromycin, Hydroxychloroquine
and Ivermectin, Camostat Mesilate - Locations: University of Kentucky Markey Cancer
Center, Lexington, Kentucky, United States - https://ClinicalTrials.gov/show/NCT04374019
25) 14 June 2020 - A Real-life Experience on Treatment of Patients With COVID 19 - Drug:
10
Chloroquine, Favipiravir, Nitazoxanide, Ivermectin, Niclosamide, Other drugs - Locations:
Tanta university hospital, Tanta, Egypt - https://ClinicalTrials.gov/show/NCT04345419
26) 16 June 2020 - A Study to Compare the Efficacy and Safety of Different Doses of
Ivermectin for COVID-19 - Drug: Ivermectin, Other: Standard treatment for COVID-19 -
Locations: Hospital Univeristário da Universidade Federal de São Carlos (HU-UFSCar), São
Carlos, São Paulo, Brazil - https://ClinicalTrials.gov/show/NCT04431466
27) 19 June 2020 - COVidIVERmectin: Ivermectin for Treatment of Covid-19 - Drug:
Ivermectin - Other: Placebo - Locations: IRCCS Sacro Cuore Don Calabria hospital, Negrar,
Verona, Italy, Policlinico S. Orsola, Bologna, Italy, Ospedale Luigi Sacco, Milan, Italy,
Ospedale di Rovereto, Rovereto, Italy, Ospedale Amedeo di Savoia, Turin, Italy, Hospital
Clinic/ISGlobal, Barcelona, Spain, Hospital La Paz-Carlos III, Madrid, Spain -
https://ClinicalTrials.gov/show/NCT04438850
28) 24 June 2020 - Ivermectin in Treatment of COVID-19 - Drug: Ivermectin - Locations:
Waheed Shouman, Zagazig, Sharkia, Egypt - https://ClinicalTrials.gov/show/NCT04445311
29) 25 June 2020 - Early Treatment With Ivermectin and LosarTAN for Cancer
Patients With COVID-19 Infection. Drugs: Placebo, Ivermectin, Losartan -
https://ClinicalTrials.gov/show/NCT04447235
30) 24 June 2020 - A Preventive Treatment for Migrant Workers at High-risk of Covid-19 -
Interventions: Drug: Hydroxychloroquine Sulfate Tablets, Ivermectin 3Mg Tab, Zinc ,
Povidone-Iodine - Dietary Supplement: Vitamin C - Locations Tuas South Dormitory,
Singapore - https://ClinicalTrials.gov/show/NCT04446104
31) 24 June 2020 - Anti - Androgen Treatment for COVID-19 - Interventions: Drug:
Dutasteride - Drug: Ivermectin - Drug: Azithromycin - Locations: Corpometria Institute,
Brasilia, Brazil - https://ClinicalTrials.gov/show/NCT04446429
32) 7 July 2020 - Worldwide Trends on COVID-19 Research After the Declaration of
COVID-19 Pandemic - Drugs: Convalescent Plasma Transfusion, Hydroxychloroquine,
DAS181, Ivermectin, Interferon Beta-1A - https://ClinicalTrials.gov/show/NCT04460547
33) 15 July 2020 - Efficacy of Subcutaneous Ivermectin With or Without Zinc and Nigella
Sativa in COVID-19 Patients - Drug: Nigella Sativa / Black Cumin , Ivermectin Injectable
Solution, Other: Placebo , Zinc - Location Shaikh Zayed Hospital, Lahore, Punjab, Pakistan
- https://ClinicalTrials.gov/show/NCT04472585
6 - News from Bangladesh, Italy, US and Israel
Let us start for news coming from Bangladesh. https://worldhealth.net/news/ Anti Aging News -
May 25, 2020 - Bangladesh Medical Team Claims Ivermectin With Doxycycline Clears COVID-19
- Archived http://archive.is/wh6uE - "A Bangladeshi medical team is claiming that their research on
the combination of two widely used and common drugs has yielded positive results in clearing
COVID-19 patients with acute symptoms of the disease. "We have got astounding results. Out of
60 COVID-19 patients, all recovered as the combination of the two drugs were applied", said
Professor Dr Md Tarek Alam, the head of medicine department at private Bangladesh Medical
College Hospital (BMCH). According to Alam who is a reputed clinician in Bangladesh the
antiprotozoal medicine Ivermectin in combination with one dose of the antibiotic Doxycycline
yielded the results of COVID-19 patients being cleared as being negative from the disease".
UNB NEWS DHAKA PUBLISH- JUNE 06, 2020, 06:21 PM UNB NEWS - UPDATE- JUNE 07,
2020, 10:35 AM - Covid-19: BMCH physician reports ‘amazing results’ using Ivermectin,
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Doxycycline. It is not the patients who decide the medication, says Dr Tarek Alam - Archived
http://archive.is/A2rc2 - "Physicians from Bangladesh Medical College Hospital (BMCH), led by Dr
Tarek Alam, claimed that a combination of the anti-parasitic drug ‘ivermectin’ with antibiotic
‘Doxycycline’ yielded amazing results against Covid-19".
https://www.thedailystar.net/ 12:00 AM, June 14, 2020 / LAST MODIFIED: 08:43 AM, June 14,
2020 - Use of Ivermectin: Hope held out, caution called for - Archived http://archive.is/Hup01 -
"Physicians at a Dhaka hospital claimed they have observed "cumulative efficacy" of ivermectin in
Covid-19 patients while using the drug in combination with doxycycline. They said although they
were yet to be certain about the exact efficacy of the drug combination, they would seek permission
from Bangladesh Medical and Research Council (BMRC) for a clinical trial to know further about
its effectiveness."
The combination of ivermectin and doxycycline is used for the treatment of other diseases (see for
instance [HOE1], [BAZ1]). Then, we have the proposal of a combination hydroxychloroquine and
ivermectin.
From Italy - https://www.trialsitenews.com/university-of-naples-federico-ii-physicians-hypothesize-why-
not-try-hydroxychloroquine-ivermectin-in-combo-against-covid-19/ May 3, 2020- Archived
http://archive.is/yFsuG "University of Naples Federico II Physicians Hypothesize: Why Not Try
Hydroxychloroquine & Ivermectin in Combo Against COVID-19?" - "Two researchers /
physicians out of the University of Naples Federico II — one of the oldest universities in the world
— introduce the use of two drugs classically used by dermatologists for the investigational use in
fighting SARS-CoV-2, the virus behind the COVID-19 pandemic. The two doctors hypothesize that
the use of Hydroxychloroquine (HCQ) and Ivermectin may evidence a consequential and
synergistic action if administered simultaneously both for chemoprophylaxis and treatment of
COVID-19". Physicians are Dr. Angela Patri and Dr. Gabriella Fabbrocini.
https://www.stampareggiana.it - 8 Aprile 2020 - Una novità importante è che oggi al San Raffaele
inizia anche la sperimentazione di un nuovo farmaco, l’Ivermectina. Archived
http://archive.is/tqnX7 - "Il suo utilizzo [Ivermectina] è stato approvato in via sperimentale
dall’AIFA, l’ente Italiano del farmaco". Dopo l'annuncio della sua efficacia in vitro, "Adesso si
ricerca la conferma clinica, si tratta di un farmaco da tempo usato contro la scabbia, i vermi ed altre
malattie prodotte da parassiti la cui specifica modalità di azione è stata chiarita. Aumenta la
concentrazione di cloro all’interno delle cellule che hanno specifici recettori, Covid 19 compreso.
Questo fatto determina la paralisi e poi la morte del virus. Ora resta la rapida sperimentazione
clinica autorizzata in Italia essendo uno dei paesi più colpiti".
Then, news from US. https://www.newsmax.com/us/ - Breakthrough Drug: Ivermectin Shows
'Astounding' Results Against Coronavirus - By David A. Patten | Friday, 22 May 2020 11:16
PM - Archived http://archive.is/uqrxr - "Doctors have administered the drug ivermectin in several
simultaneous trials in several countries sometimes in combination with other common medications.
Physicians who participated in the study report that patients’ viral loads began declining almost
immediately after they began administering ivermectin, a widely available prescription drug
approved to combat parasites, scabies and head lice. ... Emergency medical physician Dr. Peter H.
Hibberd, M.D., of Palm Beach County, Florida, told Newsmax Friday evening in an exclusive
interview that he’s optimistic the drug will prove to be an important therapeutic advance, although
he expects more trials will be needed before it wins FDA approval for use as a COVID-19
medication. He noted it has impressed doctors in clinical trials on multiple continents. In some
cases, doctors reported just one dose of ivermectin markedly improved a patient’s condition. U. S.
patients received a single oral dose, and some of them received a booster dose seven days later. The
FDA-approved dose for parasitic infections was used. ... On Thursday, a team of U.S. doctors led
by Dr. Jean-Jacques Rajter at the Broward Health Medical Center in Fort Lauderdale, Florida,
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submitted findings to an institutional review board. According to a medical source familiar with the
study, some 250 coronavirus patients were involved in the Broward trial. The results were dramatic,
with “statistically significant improvement in mortality,” according to the source".
About the mentioned trial, see https://www.trialsitenews.com/broward-county-doctor-using-ivermectin-
off-label-combo-on-covid-19-patients-it-is-working-secures-county-health-protocol-approval/ Archived
http://archive.is/IQSts (See Ref. [RAJ1]).
From Israel - https://www.jpost.com/- Israeli researcher: Antiparasitic drug could 'cure' coronavirus -
JUNE 15, 2020 - Archived http://archive.is/HADqB - "Prof. Eli Schwartz launched a clinical trial of
the drug Ivermectin, a broad-spectrum antiparasitic agent that has also been shown to fight viruses.
A tropical disease expert is testing a drug used to fight parasites in third-world countries that he said
could help reduce the length of infection for people who catch coronavirus, enabling them to go
back to work and life in as little as a few days. ... "At the onset of this virus, everyone was talking
about the anti-malaria drug,” he said, referring to hydroxychloroquine, which was first touted by US
President Donald Trump, but has since been linked to increased risk of death in coronavirus
patients, among other health risks. “We decided to look more widely for other medications and
considered a few drugs that might have antiviral activity,” he said; Ivermectin was selected".
https://www.trialsitenews.com/ - In Pursuit of Real-World Ivermectin Stories: Tales from
Pathanamthitta JUN 17, 2020 - http://archive.is/iWQu6
https://www.trialsitenews.com/ - 100-Year-Old Discharged from Mumbai’s Rajawadi Hospital after
Successful Ivermectin Treatment - JUN 18, 2020- http://archive.is/hkuON - "Now apparently
commonly in use in India, the medics at Rajawadi Hospital report that Ivermectin was the drug that
actually worked, leading to the recent discharge of 100 year old Mr. Mali. It was to the thrill of all
the staff to see this patient heal rapidly".
7 - The problem of Surgisphere - https://www.the-scientist.com/ - 16 June 2020 - Surgisphere Sows
Confusion About Another Unproven COVID-19 Drug - "The company behind a now-discredited
study on hydroxychloroquine also posted a report that has been cited by Latin American
governments recommending ivermectin as a possible coronavirus treatment. Clinicians there say the
effects have been extremely damaging". http://archive.is/G6JM6 .
This article is telling "One of the most influential studies on ivermectin’s effect in COVID-19
patients was a large observational study that used a database owned by Surgisphere, a now-
discredited Illinois-based company founded by vascular surgeon Sapan Desai. That study, published
on the preprint server SSRN in early April and updated a couple weeks later, reported a strong
positive association between ivermectin treatment and COVID-19 patient survival, and has been
cited in white papers and reports by Latin American health researchers and governments as
evidence of the drug’s efficacy". The paper in SSRN is no more available1
. About it, see please the
discussion by Carlos Javier Chaccour (he is running a clinical trial about ivermectin).
http://archive.is/d0VOd
www.the-scientist.com/ is highlighting in the web page the following: "With ivermectin firmly
entrenched in political and public minds as a weapon against the pandemic, the question of evidence
is now of secondary importance for some members of the medical and scientific communities".
Even if mitigated by a "some members", this is a serious accusation against these communities. Let
us observe that the sentence of the-scientist concerning ivermectin, that is "firmly entrenched in
political and public minds as a weapon against the pandemic", could have been applied to
1 As told in the introduction, the aim of this discussion is to understand the different approach to Covid-19 treatment,
based on ivermectin, currently running mainly in Peru. in the framework of an investigation, which started from
drugs used in Italy. It is not the discussion of SSRN paper for sure. For it, see Chaccour 's web article.
13
hydroxychloroquine too, the "Trump's 'miracle' drug", as defined in The Guardian,
http://archive.is/ToTIv . About this drug, "Praised by presidents", see "Three big studies dim hopes
that hydroxychloroquine can treat or prevent COVID-19", Jun 9, 2020, in Science,
http://archive.is/oVg7I .
8 - News from Peru and Bolivia
Let us continue with news - Fron CNN in Spanish - https://cnnespanol.cnn.com/ - Ivermectina, el
arma sin validación científica que se usa en Bolivia para tratar covid-19 - Por Gloria Carrasco, CNN
Publicado a las 16:23 ET (20:23 GMT) 29 mayo, 2020 Archived http://archive.is/17R1Y - "Bolivia
incluyó a la ivermectina dentro de la lista de medicamentos esenciales para que pueda ser usada en
el tratamiento de pacientes con covid-19. En el departamento de Beni, en el norte del país, hay una
campaña para distribuir gratuitamente este medicamento entre los pobladores del municipio de
Trinidad".
https://cnnespanol.cnn.com/ - 17:17 ET(21:17 GMT) 10 Junio, 2020 - Perú da impulso a
hidroxicloroquina e ivermectina como tratamiento para covid-19 - Por Kiarinna Parisi Archived
http://archive.is/w8KLw - Bolivia autoriza el uso de ivermectina contra covid-19 3:53 - "El
Ministerio de Salud de Perú (Minsa) dio impulso como tratamiento para el nuevo coronavirus a dos
medicamentos que carecen de autorización por parte de autoridades sanitarias o de consenso
científico sobre su eficacia y seguridad para pacientes de covid-19. ... Por su parte, la ivermectina es
un agente antiparasitario de amplio espectro, aprobado por la Administración de Medicinas y
Alimentos de Estados Unidos para ciertos usos en humanos y animales, aunque la prevención o
tratamiento contra el coronavirus no es uno de ellos. A principios de mayo, dicha autoridad
desaconsejó su uso asociado al covid-19 tras afirmar que se necesitaban más estudios al respecto".
12/6/2020 https://www.eleconomistaamerica.pe/ "El hospital de San Juan de Lurigancho empezó a
elaborar ivermectina para cubrir la demanda existente de este medicamento por parte de pacientes
afectados por la COVID-19, que llegan al nosocomio que pertenece a la Dirección de Redes
Integradas de Salud (Diris) Lima Centro, informó el Ministerio de Salud". Archived
http://archive.is/hak3F
https://exitosanoticias.pe/ - 13/6/2020 Dr. Fernández: “Si más peruanos tomaran ivermectina, habría
menos casos de COVID-19” - Usar la Ivermectina es como ponerte un chaleco antibalas contra la
enfermedad. En el Perú, más de 1 millón de personas la consumen, y nadie se ha muerto”, indicó.
Archived http://archive.is/fusra - ¿Qué hace la Ivermectina en el cuerpo? "Evita que el virus se
multiplique en las células. Por eso, la Ivermectina y la Hidroxicloroquina trabajan muy bien en
casos iniciales o cuando recién comienza la enfermedad”.
https://www.marca.com/claro-mx/ - 11/6/2020 - Hidroxicloroquina e ivermectina: ¿por qué llevan la
delantera contra el coronavirus? "Por su parte, Marcelo Navajas, Ministro de Salud de Bolivia,
emitió un permiso para la aplicación de la Ivermectina en los humanos para tratar el Covid-19 en
dicho país, aunque aclaran que su uso contra el coronavirus no está avalado por la Organización
Mundial de la Salud." -------------- web.archive.org/web/20200614112908/https://www.marca.com/claro-
mx/trending/2020/06/11/5ee18c6d268e3eaf4b8b45a9.html
https://www.connuestroperu.com/ - Miscelánea 12 Junio 2020 - La Libertad producirá 150 mil dosis
de ivermectina para luchar contra el coronavirus - El Gobierno Regional de La Libertad producirá
150 mil dosis de ivermectina para combatir el coronavirus COVID-19 en los pacientes leves.
Archived http://archive.is/BKf8q
Here also a direct experience by Dr. A. Camargo - https://www.connuestroperu.com/ - An interview
with Dr. Antonio Camargo, 02 Junio 2020 - Archived http://archive.is/Cy8Wc . "Usted contrajo la
enfermedad y se curó con ivermectina, ¿podría narrarnos su experiencia? Me infecté en mis
14
actividades laborales, atendiendo pacientes oncológicos. Un paciente que buscó ayuda y estuvo
buen tiempo en nuestro centro contagió a dos trabajadoras y la trabajadora de limpieza me infectó.
El diagnóstico de mi infección fue realizado el 8 o 9 de mayo. Tenía una carga viral terriblemente
alta, como para hacer una especie de patrón de vigilancia. Tengo un laboratorio de biología
molecular y recuerdo que el biólogo me dijo que mi carga viral era muy alta. Hasta ese momento no
sentía nada, sólo una resequedad en la garganta, sin tos ni malestar general ni fiebre, pero sabía que
se venía un “tsunami” sobre mí. Allí decidí probar en mí lo que estaba probando en otros pacientes.
De inmediato tomé 60mg por día de ivermectina, acompañando con hidroxicloroquina: 200 mg
por la mañana y 200mg por la noche, más 200mg de sales de zinc por día, que son dosis altas. Ese
fue el tratamiento coronicida. A las 48 horas me realicé un control con PCR, test molecular para
controlar mi carga viral y no había carga viral en mi faringe, no había virus".
In this interview, Dr. Camargo is reporting his experience and the use of ivermectin,
hydroxychloroquine and zinc.
9 - The case of Iquitos (Peru)
This is a specific case which deserves a detailed discussion, because we can be sure that a large use
of Ivermectin has been made. It is therefore very important for any possible statistical analysis.
https://www.connuestroperu.com/ - 13/6/2020 "El verdadero Comando COVID-19 de Iquitos: médicos
independientes lograron contener el azote del coronavirus, no el Minsa ni Essalud" - Archived
http://archive.vn/ePtmg
"Desde fines de abril a mayo las escenas diarias en los hospitales de Iquitos eran de avalancha de
infectados con el coronavirus COVID-19, que sobrepasaron su capacidad y muchos pacientes no
podían ser atendidos, mientras que otros hasta morían en los exteriores. ... Es gracias a los médicos
independientes que Iquitos superó el desastre que causó la pandemia, que ahora está controlada,
pues de no contener a muchísimos pacientes en sus domicilios con estos tratamientos exitosos,
todos ellos habrían muerto". Interview by Con Nuestro Perú with Dr. Sergio Bardon, "uno de los
médicos independientes que participaron en esta lucha y fueron el verdadero Comando COVID-19
en Iquitos".
Question: "Desde abril y mayo hay un número creciente de médicos que usan exitosamente
ivermectina, habiendo una cura. ¿A qué atribuye que internacionalmente no se difunda ello y se
prefiera a fármacos que tienen menor efecto? Answer; "Con respecto a la ivermectina lo que se ha
visto es que ha bajado en muchísimos pacientes la carga viral, es decir, la cantidad de virus que una
persona tiene en el cuerpo, y por lo tanto, va a mejorar su cuadro clínico y disminuir drásticamente
las posibilidades de que la persona se complique la infección viral".
Dr. Bardon tells also: "Lo cierto es que somos muchos los médicos que estamos usando ivermectina
con muchísimo éxito. Por supuesto, estos medicamentos tienen mayor éxito cuanto antes se recetan
y cuanto menos síntomas tiene el paciente, porque cuando llega a una fase de complicación aguda,
con una disnea importante, allí ya empiezan a actuar muchas otras cosas que no son necesariamente
la carga viral, porque es la respuesta inflamatoria que tiene cada paciente. Entonces la ivermectina
ya no tiene mucho sentido, por eso es importante no solamente darla sino darla a tiempo ...
Efectivamente, el éxito que he tenido con ivermectina es mucho. En general, a partir del tercero o
cuarto día ya en la gran mayoría de los pacientes no se han visto síntomas ni signos de COVID-19,
y con respecto a la negativización de la prueba, se obtiene también rápidamente a partir de una
semana. ... Estoy tratando a todos los pacientes en forma ambulatoria. Solamente uno tuvo que
recibir internamiento, que fue el primero. De allí todos han sido seguidos ambulatoriamente,
especialmente porque trato pacientes en Amazonas, Loreto, en lugares donde ni siquiera tienen la
posibilidad de ir a un hospital y estamos manejándolo básicamente con la asociación de
15
ivermectina-azitromicina, y hasta ahora todos han sido exitosos".
As it is evident from previous news, in Iquitos the ivermectin was used. Iquitos is the capital of
Peru's Maynas Province and Loreto Region. It is the largest metropolis in the Peruvian Amazon,
east of the Andes, and it is the ninth most populous city of Peru.
In [FRA1], it was told that the health system in this town was subjected to a very high stress for
Covid-19. "The first COVID-19 case in the Peruvian Amazon, detected on March 17, seemed to be
a one-off — a tour guide who apparently caught it from foreign visitors. Within weeks, however,
Carlos Calampa [Regional Health Director] saw patients overflowing into the corridors of the
Loreto Regional Hospital in Iquitos, where he was director". After describing the situation in the
town and Peru, the article [FRA1] ends telling "By May 25, COVID-19 cases and deaths had
dropped in Iquitos but were rising in remote areas accessible only by river or light plane, Calampa
said. He is reinforcing staff and coordinating with the military to deliver medicine, oxygen, and
other supplies to health centres on the Marañón, Corrientes, and Tigre rivers, where much of the
population is Indigenous".
It seems that something happened before May 25. And in fact, in the article of June 8, 2020,
entitled "Effective formula knocks out Covid-19 in the Peruvian Amazon", by Juan J Chamie
https://medium.com/@juanjchamie/effective-formula-knocks-out-covid-19-in-the-peruvian-amazon-
150565e9b6c6 archived http://archive.is/pI5x6 , we find the proper question "How did they get through
it so quickly?". "The numbers don’t lie. While the coastal departments (Sí Covid) haven’t stopped
the growing number of reported deaths, the main departments in the jungle region (Ex-Covid), for
example in Loreto and Ucayali, broke the trend and within three weeks drastically lowered the rise
in mortality rates. Although they still need more time to reach normal values, the trend indicates
that they’ll manage it very soon". - And then: How did they get through it so quickly? - The author
of the article in Medium tells that the "drop in deaths in the region is attributed to the general use of
a medication, and that without even having scientific evidence, according to local residents, it has
saved many lives". The drug is Ivermectin.
"In mid-April, a group of volunteers initiated a campaign in the department of Ucayali to deliver
ivermectin to residents. They openly acknowledged that they were using veterinarian ivermectin
and confirmed positive results, as well. ... Similarly, in the city of Iquitos ... an independent group
of volunteer doctors initiated a public campaign plus free vaccinations with ivermectin". This is
told in medium.com.
As we have seen in news published by www.connuestroperu.com, there are physicians such a Dr.
Bardon that, in medical clinics, are administrating the drug under their medical supervision.
However, there are also different experiences, based on groups of volunteers, that used the drug in
the veterinary formulation. Here news in http://www.perulactea.com/ on 16/05/2020 - "En Iquitos
vienen aplicando Ivermectina de uso veterinario con buenos resultados frente a Covid19". Archived
http://archive.is/yx24r
"La dosificación que se está utilizando es 1ml x 2 días. Una botella de 1000 ml Ivermecticina al 1%
de uso en ganadería, se consigue en 130 soles en las veterinarias. En pocas palabras con 130 soles
se pueden inyectar a 500 personas. [1 Sol equals 0.26 Euro] Se afirma que ya atendieron más de
2000 personas con este tratamiento, quedando claro que la Ivermectina está dando resultados
favorables para pacientes covid 19 en etapas 1 y 2. ... Desde el día martes 12 de mayo se esta
aplicando la inyección de IVERMECTINA a personas con síntomas leves de Covid 19, la atención
será totalmente GRATUITA". The article tells that the dosage of the drug that is being used is 1ml x
2 days. A bottle of 1000 ml Ivermectin at 1% of use in livestock, is available in 130 soles in
veterinary medicine. In short, with 130 soles, 500 people can be injected. It is stated that more than
2000 people have already been treated with this treatment, making it clear that Ivermectin is giving
favorable results for covid 19 patients in stages 1 and 2. Since Tuesday, May 12, the Ivermectin
16
injection is being applied to people with mild symptoms of Covid 19, the care will be totally for
free.
Let us stress once more. A large use of ivermectin has been made in this province of Peru. It would
be very interesting to have further reports about the results of the treatment, besides the report
mentioned above.
For the moment, about the Department of Loreto, we can show data from
https://bing.com/covid/local/loreto_peru?vert=graph
Fig.1 - Red dots represents the confirmed cases, the black dots the victims of the virus. Data from 16 April to 26 July.
Fig.2 - Daily new cases in Loreto, on the left- https://bing.com/covid/local/loreto_peru?vert=graph. On the right, the
purple curve represents data from Loreto, the blue curve from Callao.
The number of victims in Loreto was 259 (20 May), 288 (20 June), 368 (20 July). The last number
is 544. Then, in Loreto the percentage of fatal cases was: 544/10721=0.05 , that is 5% . What could
we deduce from the graph and numbers, about a possible effect of ivermectin? It is difficult, and we
17
need further investigation. However, the curve of the confirmed cases seems to approach the
plateau.
The image given previously (on the right) shows the comparison of cases in Loreto and Callao,
which is much more densely populated than Loreto. It seems that in Loreto, the curve is closer to
the plateau than in Callao. From https://coronalevel.com/Peru/Loreto/ , the following plot is available.
Data: Johns Hopkins University CSSE. Data from 29 May to 28 July.
Fig.3 - Data from Johns Hopkins University CSSE.
20 June 2020 - https://ojo-publico.com/1909/medicos-piden-cautela-en-uso-de-hidroxicloroquina-e-
ivermectina - archived http://archive.is/Vdy90 - "Juan Carlos Celis Salinas es médico infectólogo en el
hospital regional de Loreto, en donde las últimas semanas han atendido a cientos de personas con
Covid-19 y a muchas otras que han llegado con síntomas de haberse automedicado con ivermectina,
un fármaco usado como parte del tratamiento experimental contra el Sars-Cov-2 y que necesita un
acompañamiento clínico. “Hay personas que llegan luego de haber tomado dosis excesivas de
ivermectina, y otros que se aplican la de uso veterinario; en ambos casos llegan con efectos
adversos. Llegan con mareos, taquicardia”, sostiene".
The drug must be used under medical supervision.
10 - A drug for humans
About the concerns of using a drug involved in veterinary use, an answer was the following. “La
Ivermectina fue creada para el tratamiento de humanos” - El médico trujillano Gustavo Elera ha
frenado en seco al coronavirus en unos mil 200 pacientes en Chanchamayo con este fármaco, muy
empleado en medicina veterinaria". http://www.laindustria.pe/nota/16073-la-ivermectina-fue-creada-para-
el-tratamiento-de-humanos - dated 7 June 2020 - Archived http://archive.is/beTgM
"Desde abril a la fecha, el médico Gustavo Elera Arévalo, trujillano él, ha tratado con excelentes
resultados a mil 200 pacientes, todos en su momento afectados por el coronavirus, en La Merced,
Chanchamayo, Junín". In this article, the reporter asks Dr. Elera about the difference between
Ivermectin for human and veterinary use. Question: "En el mercado encontramos la Ivermectina
para uso humano y animal. La de uso humano ha escaseado y las pocas que se encuentran, tienen un
costo muy elevado. Así las cosas, ¿se puede emplear la veterinaria?" Answer: "Claro. No es tóxica.
18
Nosotros hemos utilizado la de uso veterinario para el penal de La Merced (Chanchamayo), para la
Policía Nacional, para todos los pacientes que estamos viendo sin ningún problema y la vamos a
utilizar en el barrido que haremos en algunos otros sectores del mismo Chanchamayo. La diferencia
entre la Ivermectina de uso humano y la de uso veterinario es que la de uso humano es Ivermectina
más agua y Sorbitol, que es un saborizante que la vuelve dulce, y la de uso veterinario es
Ivermectina más agua y punto".
We can find Ivermectin in the formulation for human and veterinary use. The formulations for
human use are in short supply and at a very high cost. So, a question is "Can we use veterinary
medicine?" Elera's answer is the following: "Sure. It is not toxic. We have used the formulation for
veterinary use for the ... The difference (in the formulation) of Ivermectin for human use and for
veterinary use is the following. The formulation for human use is Ivermectin plus water and
Sorbitol, which is a flavouring that makes it sweet. The formulation for veterinary use is Ivermectin
plus water, plain and simple. Elera' answer is translated because, in a following sections, the two
formulations of ivermectin will be discussed in detail.
Let us stress that it is necessary to check carefully the formulations, and avoid self-medication (the
use of drugs needs medical supervision). At this is clear because of different concentrations. "El
médico veterinario Eleazar Vargas señaló que la ivermectina que viene siendo usada para humanos
difiere en concentración del empleado para animales". 18 Junio, 2020 - http://archive.is/1qN3N
Dr. Eleazar Vergas is dean of the Colegio Médico Veterinario. Let us report some sentences from
this article “Hay una sola ivermectina, que se dedique para animales o para humanos ya es un tema
de concentración. Aunque creo que para humanos lo utilizan solo de vía oral”, señaló el experto a
Exitosa. It is also told, "Por otro lado, el decano del Colegio Médico Veterinario hizo un llamado a
los médicos a respetar la profesión veterinaria, luego que se generaran algunos comentarios
despectivos de algunos de ellos respecto a los puntos de vista de veterinarios sobre la ivermectina:
“creo que es una contraposición inoportuna, no es momento para decir yo soy más o yo soy menos.
He escuchado que incluso hablan del veterinario de forma despectiva, no debería ser así. Nosotros
somos profesionales de la salud”.
We can find further information about the use of ivermectin in Peru in the recent
https://elcomercio.pe/tecnologia/ciencias/ivermectina-gustavo-elera-ivermectina-el-medico-que-se-ha-
convertido-en-el-referente-nacional-de-una-campana-anticovid-19-que-carece-de-base-cientifica-noticia/ -
26 June 2020. Ivermectina - El rostro de una campaña contra el COVID-19 que crece en el Perú
pero que no tiene base científica - El médico Gustavo Elera impulsa el uso de ivermectina en
diversas regiones del país con el apoyo de alcaldes. Pese a la opinión de expertos, asegura tener la
evidencia suficiente para ello". In the article, we find that Gustavo Elera is preparing an article to be
submitted to Lancet, where he will describe the results of the use of ivermectin. It is also stressed
that "En diversos medios regionales, el médico [Elera] ha defendido el uso de ivermectina
veterinaria en lugar de la fabricada para humanos, con el argumento de que la primera es mucho
más barata. Ha asegurado, además, que “la de uso veterinario es Ivermectina más agua y punto”.
The article continues telling "Pero especialistas consultados por este Diario advirtieron que su
consumo puede traer efectos secundarios y que bajo ninguna circunstancia un medicamento para
animales debe ser usado en humanos".
And a link is given: https://elcomercio.pe/tecnologia/ciencias/coronavirus-ivermectina-covid-19-en-
ucayali-autoridades-reparten-ivermectina-para-animales-para-tratar-pacientes-con-coronavirus-noticia/?
ref=ecr/ - dated 26 May 2020, where it is told that "Dos consejeros regionales, uno de ellos del
partido Alianza para el Progreso, publicitan su iniciativa como “un acto filantrópico”. Sin embargo,
expertos subrayan que la medicina veterinaria puede ser nociva en humanos". The article has the
title: COVID-19 | Autoridades reparten ivermectina para vacas para tratar pacientes con coronavirus
en Ucayali". Veterinary medicine is a branch of medicine, working with drugs, like the ivermectin,
19
which can have formulations both for humans and animals. "Although the majority of veterinary
dosage forms contain the same drug as human dosage forms, some veterinary preparation contain
drugs that are not widely used in humans. ... Some types of dosage forms are suitable for used in
humans and certain animal species. They include parenteral solution; conventional tablets and
capsules; oral solution and suspensions" [RAM1].
Then, like many other drugs, ivermectin is not only a drug "para vacas". The highlight of
elcomercio.pe is therefore misleading. In any case, we find there a discussion about the different
formulations.
“[La presentación para animales] podría tener ivermectina como principio activo, pero no se sabe
qué más tiene. Esos otros componentes son los que pueden producir efectos no deseados”, explica
Alfonso Zavaleta, profesor de Farmacia y Bioquímica de la Universidad Peruana Cayetano Heredia
(UPCH). ... El modo de aplicación en humanos es oral, mientras que en los animales es
intramuscular. ... Ricardo Grandez, profesor de la Facultad de Medicina Veterinaria y Zootecnia de
la UPCH, alerta que si se administra esta droga por vía subcutánea e intramuscular y “se aplica
inadecuadamente, puede producir necrosis en la zona de aplicación”. “La presentación inyectable
[usada en animales] es de larga duración, tiene sustancias que liberan lentamente el principio activo.
Algunos de estos productos podrían generar reacciones en algunos individuos o en todos los
individuos".
Actually, for animals too, it is necessary to be careful and in fact, it is told "Dosis y vía de
administración: ... Vía subcutánea (S. C.) únicamente"., as at the web page of this company
https://www.vecol.com.co/productos/veterinaria/antiparasitarios/ivermectina-1, http://archive.is/YAEVk .
See also https://www.ema.europa.eu/en/documents/referral/bovimectin-injection-article-33-referral-annex-i-
ii-iii_it.pdf . For veterinary use, subcutaneous injections2
are the proper route of administration for
aqueous solutions, as we will see in the next section. Novel oil formulations can be used for
intramuscular injection too. Let us add also that it is true that ivermectin for humans is in the form
of tablets, but we have case reports about the use of subcutaneous ivermectin too, as a safe salvage
therapy [PAC1],[BAR1].
11 - Stabilized aqueous formulation
Gustavo Elera tells that the drug for veterinary use is "Ivermectina más agua y punto”. Of course,
as soon as we can read the report that he promised we will know the specific drug, the dosage, and
the route of administration. However, we have to note the following. In Ref. [KSH1], which is
discussing about ivermectin for veterinary use, it is told that "Ivermectin is generally insoluble and
unstable in aqueous preparations. Hence, to overcome the problem of poor water solubility and
obtain a stable injectable formulation of ivermectin, several commercial preparations have been
developed which use organic solvents as vehicles". High concentrations of organic solvents have
been reported to induce significant side effects [DON1], and pain and inflammation at the injection
site were commonly observed side effects of commercial ivermectin preparations [FRO1]. "The
commercially available ivermectin preparations employ different vehicles that help in stabilizing
the compound".
Table 1 of [KSH1] is giving details. One of the formulations, for parenteral and oral routes of
administration, is the following. "Stabilized aqueous formulation containing 0.1-7.5% w/v
ivermectin (Parenteral administration) with other components such as surface active agent – 0.5-
2.5% (polyoxyethylene sorbitan monoisostearate, polyoxyethylene sorbitan monostearate, and
polysorbate 80). Cosolvent – 10-60% (glycerol formal, glycerin, and polyethylene glycol) and
Substrate – 1-5% w/v (benzyl alcohol, lidocaine, parabens, and choline)". The solubilization of
2 Subcutaneous and intramuscular injections are different techniques of injection.
20
ivermectin in water is described in the patent (Inventors Pak-Kan A. Lo , James B. Williams,
Merck and Co Inc), https://patents.google.com/patent/US4389397A/en . Abstract: "Ivermectin, an
antiparasitic agent which is insoluble and unstable in water, is solubilized by the formation of
colloidal particles, called micelles, with surface active agents as solubilizers and stabilized by using
cosolvents and/or appropriate substrates in the aqueous formulation. The liquid formulations are
suitable for use as parenteral or oral administration for the treatment of parasitic infections".
In [KSH1], among the several formulations for veterinary use, in the Table 1, we can find also the
following: "Subcutaneous and intramuscular administration of a novel oil-based formulation of
ivermectin was found to be superior to the commercially available standard preparation" [LIF1].
12 - "There are no parenteral antihelminthic drugs licensed for use in humans"
Since we are talking about ivermectin for veterinary use by means of a parenteral route of
administration, we have also to add an important observation. In [MAR1], it is told that "There are
no parenteral antihelminthic3
drugs licensed for use in humans. [The authors of [MAR1]] report the
successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of
ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To [authors']
knowledge, ivermectin levels are reported for the first time in this situation". The year of
publication of the article is 2005. In [ROG1], a book of 2010, it is stressed that patients "who are
unable to absorb oral therapy present a difficult challenge as no parental preparations" of ivermectin
are licensed for use in human. However, parenteral ivermectin exists and it is that for animals.
The same, that is that "At present there are no parenteral anthelminthics licensed for use in
humans", is also told in [BAR1], an article published in 2016. And in 2020, "Regarding the
treatment, oral ivermectin is recommended for uncomplicated strongyloidiasis and is usually well-
tolerated with a higher cure rate than with albendazole. In patients with hyperinfection, and no
available oral route, therapeutic options are limited. No parenteral anti-helminthic drugs are
licensed for use in humans, but parenteral ivermectin is used in veterinary medicine. Although drug-
related toxicity, parenteral ivermectin has been used in humans as rescue therapy, appearing to be
effective and safe" ([CIP1], and references therein).
It seems to me that the only parenteral ivermectin is that for veterinary use. The use of it in rescue
therapy is effective and safe, according to publications. If this ivermectin can be the proper bullet
for Sars-Cov-2, why not use it?
13 - News propagation
As we have seen, in the region of Iquitos, Peru, physicians in their clinics used, under their control,
ivermectin. However, there were also some volunteers, in particular an evangelical group, that
treated people having Covid-19 symptoms, with ivermectin for veterinary use.
"Un grupo evangélico peruano inyecta un medicamento veterinario a miles de personas para la
covid-19". This is the title of an article in El Pais that started a sequence of news. "En Nauta, al
menos 5.000 personas la han recibido [ivermectin]”, cuenta Leonardo Tello, director de Radio
Ucamara, la principal emisora de la ciudad ubicada a dos horas de la capital de la región, Iquitos".
https://elpais.com/sociedad/2020-06-19/un-grupo-evangelico-peruano-inyecta-un-medicamento-veterinario-
a-miles-de-personas.html dated 19 June 2020, archived http://archive.is/l4IhL .
"Tello cuenta que muchas personas sintieron el aceleramiento del corazón tras recibir la inyección.
“Ha sido horroroso el efecto secundario”, relata. El director de Radio Ucamara explica que algunos
3 Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms and other internal
parasites from the body by either stunning or killing them and without causing significant damage to the host.
21
pastores evangélicos de Loreto han vinculado al nuevo coronavirus con el demonio y el fin del
mundo, ofreciendo esas inyecciones “como una salvación”. El Pais continues explaining that "En la
comunidad de Cuninico, donde gran parte de la población tenía síntomas de la covid-19, el técnico
del módulo de salud ... dijo a los voluntarios de las denominadas Misiones Evangélicas de la
Amazonía, que ya no necesitaban la “vacuna” porque la mayoría de personas se estaba cuidando
con la medicina tradicional, con plantas. Sin embargo, los enviados por el grupo evangélico
decidieron administrar la ivermectina veterinaria. "La explicación de los voluntarios fue clara y
directa de que está aprobado mediante una ley, y que es un tratamiento animal que da resultados
positivos como vacuna”, refirió el apu –jefe indígena– de Cuninico, Wadson Trujillo Acosta.
“Dijeron que lo están haciendo a nivel nacional y también en Nauta, y alertaron de los efectos
secundarios como la diarrea. A algunas personas sí les produjo esa reacción”, describió".
Adverse effects were observed, and this is due to the dose of the drug. Ivermectin is safe, if used in
the proper manner, under the control of a physician. For the side effects of accidental self-injection
and ingestions of injectable solutions, see please what is reported in the web page on ivermectin at
http://www.inchem.org/documents/pims/pharm/ivermect.htm archived http://archive.is/awBXE .
In any case, it is clear from El Pais that Tello and Acosta are giving two different versions, and that
the behaviour of the evangelical group (or better, of some of the members of the group) was wrong.
Let us see how the SUN reduces the text: https://www.thesun.co.uk/news/11934870/sick-amazon-
evangelicals-animal-drug-coronavirus-ivermectin/ archived http://archive.is/IIxsF
"He [Tello] said that many of those who had received the treatment had suffered an increase in
their heart rate whilst others have warned of diarrhoea as a side effect." The SUN is reporting
only what was told by Tello. From the SUN, we can see a further propagation in Italy. The
information was proposed by the Messaggero in the following article
https://www.ilmessaggero.it/mondo/coronavirus_farmaco_animali_amazzonia_indigeni_ultime_notizie_24_
giugno_2020-5307039.html , dated 24 June 2020, archived http://archive.is/3wAic in the following
manner: "Leonardo Tello, direttore della stazione radio locale Radio Ucamara, racconta: «Gli effetti
collaterali sono stati terribili: attacchi cardiaci, diarrea e molto altro»." That is: Leonardo Tello,
director of the local radio station Radio Ucamara, says: «The side effects were terrible: heart
attacks, diarrhea and much more».
This is not what Tello told to El Pais, and it is also quite different from what is told in the SUN.
Nobody died after having received the drug. And this is clear form the news in El Pais.
14 - Discussion in TrialSite - A Health Movement
An interesting discussion is given in the article "How a Grassroots Health Movement Led to
Acceptance of Ivermectin as a COVID-19 Therapy in Peru", https://www.trialsitenews.com/how-a-
grass-roots-health-movement-led-to-acceptance-of-ivermectin-as-a-covid-19-therapy-in-peru/ , 12 June
2020, archived http://archive.is/e9t8k - The discussion is published in TrialSite News, a digital media
dedicated to the coverage of clinical research and clinical trials, investigators and pharma. A section
is devoted to Ivermectin. Here the link https://www.trialsitenews.com/category/ivermectin/ .
"Perhaps Peru is the epicentre of the movement for off-label use of Ivermectin to treat COVID-19
patients. The doctors there swear by it. In fact, some of them curse the government for not
embracing the anti-parasite drug sooner as they believe more lives could have been saved. ... This
grassroots medical movement for Ivermectin as a treatment for COVID-19 in many ways has been
driven out of Peru as the story continues to unfold".
The web page tells that "For many weeks now, TrialSite News researchers heard a greater number
of stories about the use of Ivermectin in both Bolivia and Peru". And also "TrialSite News has
22
interviewed doctors around the world using the anti-parasitic drug to treat COVID-19 with
significant success. ... an informal network of many doctors around Peru drove a kind of community
movement to use the medicine to treat COVID-19. The government came to the conclusion that a
sufficient number of experts in that country had formed a consensus that couldn’t be ignored".
TrialSite News tells that university-based documents exist, "floating around in Peru that may have
led to the off-label use and, ultimately, the approval". A title is given "Therapeutic Plan that
includes Ivermectin in the First Line of Action" (see https://archive.vn/aCprF ). To my best
knowledge, no document is available in English. Gustavo A. Aguirre-Chang seems to be the
author of the document entitled "INCLUSIÓN DE LA IVERMECTINA EN LA PRIMERA LÍNEA DE
ACCIÓN TERAPÉUTICA PARA COVID-19. Se reporta una muy significativa disminución de la Tasa de
Letalidad con su uso". Lima, Perú. 2 de Mayo del 2020. Available at https://megalabs.global/ -
http://archive.is/x12Co . In the paper, the author is telling that "Por su parte, en República
Dominicana, el Médico Neumólogo J. Tavares reporta que va tratando 247 pacientes con
Ivermectina con respuesta favorable en todos los casos y no ha manifestado ningún caso fatal. De
manera similar, a nivel local, si bien a la fecha aún no son muchos los casos documentados, la Tasa
de Letalidad viene siendo 0% y además se observa que en el 100% de los casos tratados con
Ivermectina se presenta una mejoría de la enfermedad y resolución de la fiebre dentro de las 48
horas de iniciado el tratamiento". Aguirre-Chang is detailing of 82 cases in Peru4
.
The TrialSite is also telling that Gustavo A. Aguirre-Chang, in mid May, commented in a Reddit
group "that his group had treated 39 COVID-19 cases and that the Ivermectin regimen was quite
successful for “those who complete the indicated treatment and undergo medical follow-up.” Dr.
Aguirre-Chan reported that 1) patients with the disease were showing improvement within 2 and 3
days of starting treatment (100% of the 36); 2) fever resolution rate at 36 hours of taking ivermectin
was at 94% and 3) resolution rate of dyspnea (difficulty breathing) at 72 hours was 86%."
Let us continue with the discussion in TrialSite. In Peru, "Doctors went about using Ivermectin and
reporting on positive results to colleagues. Conservative forces there resisted noting, after all, this
drug was for animals". "For Animals: Humans Need Not Try. ... the first line of defense against
this drug, at least in the developed “first world,” was that Ivermectin was an “animal drug.” This
sort of bias was evidenced clearly by the FDA’s Ivermectin warning. Titled “FAQ : COVID-19 and
Ivermectin Intended for Animals,” the FDA took overt advantage of a loaded headline to convey an
underlying point. ... But did they think anyone would take them seriously? But it was Created for
Humans. In reality, Ivermectin was in fact created for humans. In Peru, doctors are treating
COVID-19 patients with one drop every 24 hours for two days and many physicians report within a
month they see patients fully recovered". We have discussed before the formulations for humans
and veterinarian use.
TrialSite tells that "Prominent researchers and industry observers were obviously skeptical and
downplayed the Monash findings5
, arguing that studies in humans weren’t feasible due to dosage
and other factors". As we have seen, many scientists and physicians are running 33 clinical trials
with ivermectin. TrialSite continues: "However, in nations that struggle with poverty and lack of
access to more expensive drugs, such as remdesivir, physicians had to chart their own course.
Hence, dozens if not hundreds of doctors around the world are prescribing ivermectin in COVID-19
patients; Peru perhaps can be considered the epicentre of that movement. TrialSite News has
interviewed a handful of these doctors and they all report the same thing: that the anti-parasite
drug ... actually works better than remdesivir. This finding is heard from doctors all over the world;
TrialSite News has interviewed physicians in Bangladesh, France, India, Brazil and the United
4 Aguirre-Chang is also reporting the interest of MedinCell for an injectable formulation of ivermectin, see
https://www.trialsitenews.com/medincell-continues-its-investigational-pursuit-of-ivermectin-targeting-covid-19-
patients/
5 That is, the results reported in [CAL1].
23
States not to mention Peru, Bolivia and Mexico. ... TrialSite News recently interviewed a contact in
Peru, a PhD in Public Administration and Computer Science, that happens to be active in the
Ivermectin movement there. He reports that in the city of Iquitos, a place known for scary tropical
diseases, the widespread use of Ivermectin has led to a steep drop in the number COVID-19 cases".
As we have seen, we can find news telling that there is a large use in Peru of ivermectin. In the
TrialSite it is stressed that the use of this drug is linked to a health movement, which has
government support. When compared to the number of physicians in the world, the "dozens if not
hundreds of doctors around the world" is a small number, but it important to know, when possible,
their experiences in specific reports, in particular for the case of Iquitos.
15 - Further news until 20 July and a report from Dr. T. Alam
Trafficking drugs: a problem related to pandemic. SANTA CRUZ - Arrestan a dos personas por
venta de ivermectina con precio sextuplicado - 29 June 2020 - http://archive.vn/GWW7f and also
Ivermectin trafficking - "Dois homens são flagrados com 250 caixas de ivermectina contrabandeada
da Bolívia em MT [Mato Grosso]; remédio é usado contra Covid-19 - Além de ivermectina, eles
também contrabandearam 25 caixas de levofloxacino hemi- hidrato, nove caixas de Paracetamol e
14 caixas de Ibuprofeno. Toda a mercadoria está avaliada em R$ 8 mil. - 29/06/2020 10h51 -
http://archive.vn/K4pLG
The Gorvernor of Mato Grosso - “Não tomei cloroquina. Nada contra, mas ... ”. O governador
afirmou que fez uso de dois comprimidos de Ivermectina por um dia. O remédio é um anti-
helmíntico (vermífugo), que em estudo in vitro teria demonstrado capacidade de reduzir a
duplicação do vírus e impedir a entrada dele nas células. No entanto, poucas evidências demonstram
sua eficácia". 09/06/2020 - http://archive.vn/sHWX5
Once more we find - On Jul 7, 2020 - "Animal products not intended for COVID-19 treatment" -
https://www.kmaland.com/ag/animal-products-not-intended-for-covid-19-treatment/article_a7e78cdd-c7df-
572c-8a95-2f1194761e52.html - archived http://archive.vn/aWjsQ - "As the public became aware of the
research paper there were growing concerns about people wanting ivermectin to treat COVID-19 --
and self-medicating by taking ivermectin products intended for animals".
"Latin America is battling some of the world's most devastating coronavirus outbreaks, and is also
facing the scourge of fake cures and unproven treatments promoted on social media across the
region." 12 July 2020 - https://www.bbc.com/news/53361876 - "Along with many other drugs,
ivermectin's effectiveness against Covid is being evaluated in clinical trials. But the PAHO has said
studies so far "were found to have a high risk of bias, very low certainty of the evidence, and that
the existing evidence is insufficient to draw a conclusion on benefits and harms. Ivermectin "is
incorrectly being used for the treatment of Covid-19" says the PAHO, "without any scientific
evidence of its efficacy and safety for the treatment of this disease". Despite this, health officials in
Peru, Bolivia and parts of Brazil have endorsed and administered the drug - and it has been widely
sold".
In the Section 6, we have already seen that Dr. Alam reported of results on the use of Ivermectin.
Here further news - Dr Tarek Alam: Unleashing the potential of Ivermectin - UNB NEWS DHAKA
PUBLISH- JULY 19, 2020, 12:22 PM - https://unb.com.bd/category/special/dr-tarek-alam-unleashing-the-
potential-of-ivermectin/54846 - archived http://archive.is/XFQLe . For Covid-19, as we have previously
seen, it was used a combination of "two cheap, easily available drugs". The article tells that the
combination of drugs eas success in reducing the viral load and restricting the severity of disease.
"Apparently 98 percent of Covid-19 patients get cured with the combined use of anti-parasitic drug
Ivermectin and antibiotic Doxycycline within 4-14 days, said Dr Tarek Alam, the renowned doctor
who has been leading a team of BMC physicians in a study during the course of treating patients at
24
the hospital attached to BMC. They recently reported tremendous success with the two-drug
combination treatment against the virus during its study that started on April 15 last. “What we’ve
found is that it’s better to use the two drugs as soon as possible after a person is tested positive or
symptom is seen,” Dr Alam said in a virtual interview with UNB. “We used the drugs within 5-6
days on all patients (and almost all got cured). Actually it needs to conduct further study whether
these (drugs) will be effective in case of use after the time,” he said, adding that so far the drugs
have been used on “some 400-500 Covid patients” since April. But only “4-5 patients” having
diabetes and heart problems or who delayed in getting the treatment needed to go to Intensive Care
Unit (ICU). And two patients died despite being administered with Remdesivir and plasma
therapy".
16 - Not all doctors
Let us go back to news from Peru. As we have previously seen, there is a health movement - as
defined by TrialSite - in Peru, driven by physicians. From news we known that it is supported by
the Government. However, some "Médicos peruanos piden detener el uso de la hidroxicloroquina
e ivermectina en pacientes COVID-19" - 30 June 2020 ----------------------
https://larepublica.pe/sociedad/2020/06/29/coronavirus-peru-medicos-piden-detener-el-uso-de-la-
hidroxicloroquina-e-ivermectina-en-pacientes-covid-19-carta-abierta-al-minsa/ , http://archive.vn/YbsuR -
"Los doctores ... se mostraron preocupados por el uso de la hidroxicloroquina y la ivermectina que
impulsan las autoridades sanitarias en el país como tratamiento para la COVID-19". This is
important. And also here https://www.estrelladigital.es/articulo/america/medicos-peruanos-piden-detener-
uso-hidroxicloroquina-ivermectina-pacientes-covid-19/20200630102348422556.html archived
http://archive.is/7UAD0 - "Los doctores Julio Chirinos, médico internista y cardiólogo (Universidad
de Pensilvania), Vicente Corrales, médico internista e infectólogo (The Ottawa Hospital) y Germán
Málaga, médico internista (Universidad Peruana Cayetano Heredia) se mostraron preocupados por
el uso de la hidroxicloroquina y la ivermectina que impulsan las autoridades sanitarias en el país
como tratamiento para la COVID-19. Los especialistas precisaron que ambos medicamentos son
recomendados por el Minsa, pero numerosos estudios de importante credibilidad han reportado una
falta de efectividad por parte de los fármacos cuando se aplican con la finalidad de tratar la COVID-
19. Tras haber difundido la misiva el pasado 17 de junio, el grupo de galenos no ha obtenido una
respuesta concreta, pero confía en que establecerá un diálogo oficial y sincero con los
representantes de la cartera ministerial".
The Carta Abiertas is available at https://it.scribd.com/document/466257700/Carta-Abiertas-sobre-las-
recomendaciones-del-MINSA-sobre-el-tratamiento-con-medicamentos-de-COVID-19-en-el-
Peru#from_embed
17 - US monopolises Remdesivir
A very interesting discussion - US monopolises COVID-19 treatment drug. Which countries are
missing out? - https://www.sbs.com.au/news/dateline/us-monopolises-covid-19-treatment-drug-which-
countries-are-missing-out (web site visited 8 July 2029) - "The US has bought most of the globes’
supply of remdesivir, an antiviral drug that could help treat COVID-19. The Trump administration
has purchased more than 500,000 doses of remdesivir -- that’s almost all of the world’s supply for
the next three months. The antiviral could help treat COVID-19 by improving the recovery time for
hospitalised patients. It is not a cure". About Peru it is told - "Unless the country has its own stocks
of remdesivir, it’s unlikely Peru will have access to the drug in the next months. Last month,
officials spruiked ivermectin, an antiparasitic commonly used in tropical medicine, as a COVID-19
treatment. The Pan American Health Organization, a regional office of the World Health
Organization, has issued a statement warning against the use of ivermectin to treat COVID-19. The
25
Peruvian Ministry of Health also promoted hydroxychloroquine has an effective treatment". If US
possesses Remdesivir - if it is useful or not is another problem - what can the rest of humankind
use?
18 - From Bulgaria, India and Brazil
On July 6, 2020 - "Bulgarian Team Close to Finding a Treatment for COVID-19" -
https://www.novinite.com/articles/205180/Bulgarian+Team+Close+to+Finding+a+Treatment+for+COVID-
19 , archived http://archive.vn/EBN7l - "In May, a clinical trial with the drug Ivermectin was
launched in Bulgaria. The team is Bulgarian, and so is the manufacturing company. So far, 30
patients have been recruited for it. The clinical trial is being conducted in 9 hospitals in Bulgaria,"
Kirilov [director of Bulgarian Drug Agency] said. "Bulgaria was the first country in the EU to
launch such a clinical trial, followed by Spain, Brazil and the United States. We hope to have
primary results by the end of the month." "
7 July 2020 - "Grupo de 478 médicos do DF elabora protocolo para tratamento precoce da Covid-19
Documento com sugestão de medicamentos foi entregue à Secretaria de Saúde e inclui
hidroxicloroquina e ivermectina" - https://www.metropoles.com/colunas-blogs/grande-angular/grupo-de-
478-medicos-do-df-elabora-protocolo-para-tratamento-precoce-da-covid-19 - "Um grupo com 478
médicos da rede pública e privada do Distrito Federal se reuniu para elaborar e propor um protocolo
de tratamento precoce de pacientes infectados pelo novo coronavírus. Na lista de medicamentos a
serem ofertados aos doentes está a hidroxicloroquina, além do vermífugo ivermectina e do
antibiótico azitromicina. ... “Temos medicações que estão disponíveis, são de baixo custo, baixa
toxicidade e que podem ser prescritas pelos médicos no primeiro estágio da Covid-19 para diminuir
a replicação viral. É claro que todos nós gostaríamos de trabalhar com base em estudos científicos
sólidos. Mas vivemos uma situação atípica, de guerra. O novo coronavírus não está na bula, porque
ele não existia quando os medicamentos foram criados”, explica a otorrinolaringologista Carine
Petry, uma das integrantes do grupo.
On 3 July 2020 - https://www.nationalheraldindia.com/india/delhis-ln-hospital-to-discontinue-anti-viral-
drug-favipiravir-for-covid-19-treatment - "Delhi’s LN Hospital decides against using anti-viral drug
Favipiravir for COVID-19 treatment. The LN Hospital committee approved the use of three other
drugs – Remdesivir, Tocilizumab and Ivermectin – and plasma therapy in the treatment of COVID-
19. ... The committee acknowledges that though Ivermectin has shown only laboratory evidence as
an inhibitor of the COVID-19 causative virus, it should be considered for hospitalised patients
because it is a cheap drug, easily available and is known to be safer than other drugs. Its side effects
are only fever and skin rash. This drug, which has been approved by the US FDA for parasitic
infections, could help in limiting the viral load and prevent severe disease progression, according to
the doctors at LN Hospital".
19 - a - SSRN or Antiviral Research
As we have previously seen, a working paper was published in SSRN and then retracted by the
authors. For this reason, I have not discussed it above. In Google Scholar it appears as "Ivermectin
in COVID-19 related critical illness, SSRN 3570270, 2020 - papers.ssrn.com - "A pre-clinical
study, demonstrated that ivermectin, FDA approved as an anti-parasitic agent with an established
safety profile ...". I repeat, the paper was withdrawn from SSRN by the authors. However, we have
to mention SSRN for the following news.
5 July 2020 - "San Marcos: tratamiento con ivermectina tiene menos tasa de letalidad" -
https://www.radionacional.com.pe/noticias/locales/san-marcos-tratamiento-con-ivermectina-tiene-menos-
tasa-de-letalidad - La tasa de letalidad en los pacientes que usaron ivermectina en su tratamiento
26
contra el covid-19 fue 6.1 veces menor en comparación con los pacientes que no lo usaron, según
un estudio realizado por el médico egresado de la Universidad Nacional Mayor de San Marcos
(UNMSM), Gustavo Aguirre". The same in http://laindustria.pe/nota/16663-tratamiento-con-
ivermectina-tiene-menos-tasa-de-letalidad and in https://libero.pe/ocio/1570733-coronavirus-peru-estudio-
revela-100-pacientes-covid-19-trato-ivermectina-mejoraron-minsa - After two days - 7 July 2020 -
"Ivermectina y COVID-19: los errores y mentiras detrás de un “estudio” viral de dudosa calidad" -
https://elcomercio.pe/tecnologia/ciencias/ivermectina-covid-19-coronavirus-los-errores-y-mentiras-detras-
de-un-estudio-viral-de-dudosa-calidad-noticia/ .
The elcomercio.pe is not giving links to documents. However, it seems - due to published
screenshot - it is the same of that at http://archive.is/x12Co ). The elcomercio.pe tells the research
"había sido publicada en Antiviral Research. El Comercio comprobó que el estudio no figura en
esta revista médica internacional". In the document, Dr. Aguirre Chang does not tell that his work
has been published in the Antiviral Research journal. The document seems being a working paper.
In any case, let us stress that the paper published in the Antiviral Research journal is Ref.
[CAL1]. In Aguirre's working paper (http://archive.is/x12Co), there was a mistake in abstract and
text. It was told that the document in SSRN has been placed on the web site of Antiviral Research6
.
This mistake raised confusion, enhanced by elcomercio in the news. SSRN working paper is no
more available, because it has been withdrawn. Let us forget it, but ask for results obtained by
physicians that used ivermectin.
It seems to me that Aguirre's document to consider is [AGU1]. "RESULTADOS: Se trataron con
Ivermectina 33 pacientes adultos con Síntomas Persistentes de COVID-19. En el 97% de los 33
pacientes tratados con Ivermectina se encontró mejoría clínica después de las 2 dosis de
Ivermectina. La mejoría clínica fue total en el 87.9% de los pacientes después de la 2da dosis de
Ivermectina. En el 12.1% de los pacientes se requirió dar más días de tratamiento con Ivermectina,
pero con esto se logró una mejoría clínica y remisión de los síntomas en el 100% de los casos.
CONCLUSIÓN: El resultado del presente estudio encuentra efectividad del tratamiento con
Ivermectina de los pacientes con Síntomas Persistentes de COVID-19, observándose una mejoría
clínica en el 100% de los casos".
As we have previously told, Dr. Aguirre is reporting, in the previously mentioned documents, of
several cases in Peru. We are also waiting for the report of Dr. Elera, as he promised to
elcomecio.pe (see the news previously mentioning him) and from all the other doctors engaged in
the Health Movement. The reason is the following: to test the efficacy of ivermectin.
19 - b - Un breve commento sul documento in SSRN, ora ritirato
Il lavoro pubblicato su SSRN (16 Aprile) ed ora ritirato, autori con affiliazioni negli Stati Uniti,
sosteneva l'efficacia dell'ivermectina in pazienti ricoverati per Covid-19 in terapia intensiva. Lo
studio era retrospettivo tra il primo Gennaio del 2020 ed il 31 Marzo del 2020. Si dice che si sono
analizzati in Europa 107+120=227 casi. Guardate i dati delle vittime in Italia, Francia, Spagna,
Regno Unito. Vi sembra possibile che in Europa, avendo ottenuto in qualche caso buoni risultati
con l'ivermectina, essa non sia stata usata per evitare le stragi da Covid-19? Pensate a questo. In
ogni caso, i dati non potevano provenire dall'Italia, dove, secondo le notizie, solo da Aprile, nello
specifico l'8 Aprile, si sarebbe autorizzato l'uso dell'ivemectina in test clinici, a seguito della ricerca
pubblicata in [CAL1].
The work published on SSRN (April 16) and now withdrawn, authors with affiliations in the United
6 Aguirre-Chang has revised the text. The new version is at https://www.researchgate.net/publication/342466502
_INCLUSION_DE_LA_IVERMECTINA_EN_LA_PRIMERA_LINEA_DE_ACCION_TERAPEUTICA_PARA_COVID-
19_Se_reporta_una_muy_significativa_disminucion_de_la_Tasa_de_Letalidad_con_su_uso - See also
http://archive.is/vwHOs
27
States, supported the efficacy of ivermectin for patients in hospital intensive care units for Covid-
19. The study was retrospective, between 1 January 2020 and 31 March 2020. 107 + 120 = 227
cases are said to have been analysed as coming from Europe. Look at the data of the victims in
Italy, France, Spain, and in the United Kingdom. Does it seem possible to you that in Europe,
having in some cases obtained good results with ivermectin, it has not been used to avoid the
massacres of Covid-19? Think about this. In any case, data could not come from Italy, where,
according to the news, the use of ivermectin in clinical trials was authorized just from April, the 8
of April, after the results published in [CAL1].
In my opinion, but I have to check it, ivermectin was not used in Europe to treat Covid-19 from the
first of January to the end of March, not used at all. Therefore, I want to tell once more to forget
this damned SSRN preprint. There is no point in the news continuing to bring it up. Let us
concentrate on the results obtained by physicians who are using ivermectin.
20 - Rare symptoms of Covid-19 - a report from Dr. E. Durand, Lima
As previously told, ivermectin has a large use in Peru. This fact gives the possibility to receive
specific reports from physicians about the efficacy of it in the treatment of Covid-19 patients. At the
same time, these reports can evidence new facts about the disease and consequently improve the
knowledge about the effects of Sars-Cov-2 on human bodies. Here in the following an important
example.
"Perú: médico que ha tratado más de 3,000 pacientes de coronavirus reporta raro síntoma en
mujeres y confirma eficacia de la ivermectina" - Lima, Peru - 27 Julio 2020 -
https://www.connuestroperu.com/ciencia-y-tecnologia/salud/66246-peru-medico-que-ha-tratado-mas-de-3-
000-pacientes-de-coronavirus-reporta-raro-sintoma-en-mujeres-y-confirma-eficacia-de-la-ivermectina -------
archived http://archive.is/YKGWv
"Un síntoma raro ha sido observado en pocos pacientes contagiados con el coronavirus COVID-19
en Lima y se presenta en mujeres. El doctor Eduardo Durand, quien ha atendido en la práctica
privada a más 3,000 pacientes con coronavirus, reporta síntomas raros en pocos pacientes.
Consisten en debilidad de los miembros inferiores acompañada de dolor lumbar, que hasta el
momento ha observado en cinco pacientes mujeres. El galeno, de Consultorios Médicos San Luis,
Lima, señala que junto con estos síntomas, las pacientes presentaron también dolor de oído,
sensación de frío en la espalda y ardor en los ojos. Las pacientes, de edades de 30 a 65 años,
pasaron por análisis de prueba rápida y radiografía de tórax. Todas recibieron tratamiento que
resultó satisfactorio con su recuperación gradual en un promedio de diez días."
Rare symptoms have been observed in few Covid-19 patients in Lima and occurred in women.
Dr. Eduardo Durand, who has treated more than 3,000 patients with coronavirus in his
private practice, reports about them. The symptoms consist of weakness of the lower limbs
accompanied by low back pain, which have been observed in five female patients so far. Dr.
Durand, Consultorios Médicos San Luis, Lima, pointed out that, along with these symptoms,
the patients also presented ear pain, a feeling of cold in the back and burning eyes. The
patients, aged 30 to 65 years, underwent rapid test analysis and chest radiography. They all
received a treatment that was effective for their gradual recovery in an average of ten days.
The reports continues about ivermectin. "Eficacia de la ivermectina - El doctor Durand destaca la
eficacia de la ivermectina y considera a este fármaco un gran y rápido aliado, y destaca su fácil
accesibilidad. Tanto las pacientes con estos síntomas raros, como más de tres mil pacientes,
superaron la enfermedad en estados leve a moderado, a los cuales prescribió de una a dos gotas de
ivermectina por kilo de peso, según el grado de complicación, sin haberse observado efectos
28
adversos, salvo un caso de diarrea. Recomendación a la ciudadanía ante el aumento de contagios y
fallecimientos. El galeno recomienda a la ciudadanía estar alerta a los síntomas de esta enfermedad
y no dejar que avance, pues puede requerir hospitalización en un momento en que los hospitales
están saturados. De igual forma, no deje pasar el tiempo con calmantes. Indica que si en la zona en
que se encuentra no hay pruebas de descarte, deje que con diagnóstico de síntomas su médico inicie
el tratamiento, pues por televisión se ve a personas esperando días por la prueba sin inicio de
tratamiento, con lo cual van camino al agravamiento porque es una enfermedad que avanza a gran
velocidad."
Eduardo Durand highlights the efficacy of ivermectin and considers this drug a great and fast
allied agent, of easily availability, against Covid-19. The patients with rare symptoms, such as his
other Covid-19 patients - more than 3,000 -, overcame the disease in mild to moderate states.
Ivermectin was prescribed according to the state of patient. Adverse effects have not been
observed, except for a case of diarrhea. Actually, Dr. Durand recommends not letting the
symptoms of the disease progress, in order to avoid hospitalization. In the case that it is not possible
to test for Sars-Cov-2 infection, when symptoms are observed, it is better to ask a doctor for starting
a treatment as soon as possible to avoid the aggravation of the disease. Covid-19 is a disease that
progresses rapidly.
The rare symptoms observed and reported by Dr. E. Durand, Consultorios Médicos San Luis, Lima,
Peru, have to be added to the list of the neurological associations of the disease published in
[ELL1].
21 - Making ivermectin for oral use (6mg/mL)
As we have discussed before (see Section 13), it happened that ivermectin for veterinary use had
been injected in many persons with Covid-19. In fact, ivermectin for parenteral route of
administration is existing only in the veterinary formulation. The use of this formulation in rescue
therapy is effective and safe, according to publications. In fact, the drug for veterinary use must be
safe, because accidental self-injection and ingestions are possible. See cases in
http://archive.is/awBXE . Ivermectin is generally well tolerated. "Only side effects have been
reported: itching, swollen lymph glands, dizziness, hypotension, fever, headache and myalgia.
Side effects are more frequent and severe in patients with high microfilaria counts. Other persons at
risk include veterinarians and farm workers involved in treating animals for worms and
ectoparasites. Most cases reported involve accidental self-injection and some ingestions of
injectable solutions. No human deaths have been reported".
However, some web sites of newspapers raised concerns about the use of ivermectin for parenteral
route of administration, in particular elcomercio.pe as we have seen. On 28 June, the same web site
gives the important news. https://elcomercio.pe/peru/coronavirus-peru-san-martin-essalud-moyobamba-
comenzo-a-producir-ivermectina-con-capacidad-de-20-mil-dosis-mensuales-nnpp-noticia/ , we read that
ivermectin for oral use is produced in a local hospital. "Una excelente noticia para la región San
Martín dio a conocer EsSalud-Moyobamba, tras anunciar que viene produciendo ivermectina para
el tratamiento de pacientes con COVID-19, a cargo del área de Farmacotecnia del Hospital II-1 Alto
Mayo que está en capacidad de elaborar 20 mil dosis mensuales. ... Asimismo, la composición de
ivermectina incluye alcohol etílico, propilenglicol, sorbitol e ivermectina de uso médico (sólido), y
será suministrado bajo prescripción médica". The same, that is the production of ivermectin for oral
use to treat Covid-19, is happening in other hospitals is Peru.
In fact, a document dated 23 June 2020 of the Peruvian Government exists which is giving the
formulation. https://cdn.www.gob.pe/uploads/document/file/874053/RM_426-2020-MINSA.pdf
29
Formulation from MINSA, Peru.
22 - Data
As we can appreciate in the news from Peru - and South-America, in general - it seems that a large
use of ivermectin is and will be made for Covid-19. It is therefore clear that an efficacy of the drug
can be easily evidenced by the numbers about new, active cases and victims in the country. In the
plots given below, proposed by the www.worldometers.info for Peru, it is reasonable to imagine
that the curves, about new and active cases, and victims, can be influenced by any efficacy of the
drug.
Fig.4 - Daily New Cases. The blue line represents a 7-days moving average.
Fig.5 - Number of infected people (active cases).
30
Fig.5 - Daily victims. Red line represents a 7-days moving average.
The data (15 February - 27 July, are a courtesy of worldometers.info, available at
https://www.worldometers.info/coronavirus/country/peru.
The number of the daily cases is increasing, but the number of victims of the virus seems to have a
decreasing trend in the last days of July.
Acknowledgement
I would like to offer my special thanks to Dr. Rocio Ferrel for her precious support on literature and
news concerning Ivermectin.
Appendix A
Not only ivermectin is under investigation. 16 June 2020 - "Broad-Spectrum Antiparasitic Drug
Ivermectin Could Help `Cure` COVID-19" is told" by https://www.hospimedica.com/covid-
19/articles/294782974/broad-spectrum-antiparasitic-drug-ivermectin-could-help-cure-covid-19.html
archived http://archive.vn/mOV0b - The article is reporting about the clinical trial led by Eli
Schwartz, Sheba Medical Center (Tel Hashomer, Israel). But it is also telling the following.
"Another anti-parasitic drug niclosamide tested on ferrets in a study by Daewoong Pharmaceutical
Co., Ltd. (Seoul, Korea) was found to have eliminated the novel coronavirus from their lungs.
According to Daewoong, its experimental anti-viral drug completely cleared up the disease in the
lung tissues of ferrets and the company now plans to start human clinical trials in July with approval
of the COVID-19 treatment drug expected by the end of this year". Niclosamide is nentioned in trial
https://ClinicalTrials.gov/show/NCT04345419 .
In [XIN1], a study of possible drugs against Sars-Cov-2, it is told "Interestingly, three anti-parasitic
drugs pyrvinium, ivermectin, and niclosamide were ranked among the top 30 predicted drugs. Both
ivermectin and niclosamide were shown to inhibit the replication of SARS-CoV-2 in vitro (Caly et
al. 2020; Jeon et al. 2020), and pyrvinium and niclosamide were shown to be effective against
MERS-CoV and SARS-CoV (Shen et al. 2019; C.-J. Wu et al. 2004)".
In [KAN1], it is told: "Niclosamide: Another medication undergoing repurposing investigations for
SARS‐CoV‐2 is niclosamide, an oral anthelmintic drug used worldwide at a single dose of 2 g/d.
Niclosamide exerts anti‐MERS activity, inhibits SARS‐CoV replication and abolishes viral antigen
31
synthesis in vitro, (Refs. 51,52 of [KAN1]) and therefore, is considered a possible treatment option.
However, it is cytotoxic and has low absorption including low oral bioavailability (10%) and
although efforts have been made to formulate derivatives to overcome these obstacles, its extensive
clinical development as an antiviral agent may still be hindered. An interventional trial has been
registered to evaluate the use ...". As we have told before, Ivermectin is safe.
See also Ref. [PAU1]: "Clinical trials on the repurposing of some anthelmintics (Nitazoxanide,
NTZ; Ivermectin, IVT; Niclosamide, NCL) for COVID-19 seem to be based on in vitro data
showing that these compounds inhibit replication of a variety of viruses in cell culture assays. NTZ,
for instance, was active in cell culture assays against a broad range of influenza A and B, as well as
other RNA and DNA viruses, such as RSV, parainfluenza, coronavirus, rotavirus, norovirus,
hepatitis B and C viruses, dengue, yellow fever, Japanese encephalitis and HIV. Likewise, in in
vitro tests, IVM inhibited the replication of a broad range of viruses (dengue, West Nile virus, HIV,
simian SV-40, influenza and others) and strongly repressed SARS-CoV-2 virus replication in Vero-
hSLAM cells. Also in in vitro assays, NCL proved to be a potent inhibitor (nanomolar to
micromolar range) of replication of SARS-CoV, MERS-CoV, zika virus, hepatitis C virus and
human adenovirus. NCL had been reported to be active (in vitro) against SARS-CoV at
concentrations as low as 1.56 μM in 2003". See also [JXU1] , [POO1].
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