[-] TrumpLyftAlles | 2 points | Jul 11 2020 00:29:06

ATTENTION! When I posted this to twitter on 2020-07-10, I said I would fix the links today. Unfortunately, I have other chores to deal with, so the links are NOT fixed. I'll put notice here when they are. Might be next week.

The PDF is weird in having a bit of Italian and quite a bit of Spanish. This is a recreation of the PDF in just English. It is complete except (1) it eliminates some in-line citations because I'm lazy and (2) it omits a list of the 32 clinical trials, which I simulate with a link (it will stay updated).

A great thing about the article is its many links, esp. to archive.is. Doubtless I'll find a few that haven't made it to this sub (yet).

This article is LONG so it has to be posted in 11 chunks because of reddit's 10,000 character limit on posts.

#Ivermectin for Covid-19

Amelia Carolina Sparavigna

Politecnico di Torino (Polytechnic of Turin)

Discussion of scholar papers published until 10 July, 2020, on Ivermectin, and of news that we can find about its use for Covid-19. A list of clinical trials is also given. For what concerns scholar papers, we report among them a preprint posted on 10 June in MedRχiv, which concludes that Ivermectin was associated with lower mortality during treatment of Covid-19. We report also the preprint posted on 8 July in MedRχiv, showing the result of a clinical trial. The preprint tells in the conclusions that add-on use of Ivermectin is giving better results when compared to controls, in particular a significant shorter hospital stay. From news, we consider in particular the case of Iquitos, capital city of the Loreto Region in Peru, where, by May 25, Covid-19 cases and deaths had dropped notably. 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 10, 2020 - DOI 10.5281/zenodo.3893750

In [1], an article which is discussing the drugs used in Italy for the treatment of Covid-19, we mentioned the Ivermectin. In [1], published on 9 May 2020, we reported the news "Positive news on Remdesivir and other drugs COVID-19 / Drugs ", dated 7 May and written by Ernesto Carafoli and Enrico Bucci, archived http://archive.is/YdIqh. There it is told that "The last drug arrived on the Covid-19 scene that is worth mentioning is Ivermectin: a pesticide known for its its broad-spectrum antiviral activity also used in human therapy for dermatological conditions. A interesting Australian study has shown that its addition to cells infected with SARS_CoV2 reduces the level of infecting RNA in 48 hours by 5000 times. However, some must be considered."

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 the 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 want to do in France.

Let us see the scholar papers published until now on Ivermectin and the news that we can find about its use for Covid-19. For what concerns scholar papers, we also report a preprint posted on 10 June in MedRχiv which concludes that Ivermectin was associated with lower mortality during treatment of COVID-19. From news, we consider in particular the case of Iquitos, Peru. In this city, by May 25, Covid-19 cases and deaths had dropped notably.

#Nobel Prize Before discussing literature and news, let us remember the extraordinary history of the drug. Ivermectin is a drug derived from avermectin. Actually, avermectin is 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.

#Scholar literature 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 [2]. Ref. 2 is the origin of researches, trials and use of Ivermectin. The authors - 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 SARSCoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans".

However, some objections exist. We can find them given in [3]. In the abstract it is told that "Caly, Druce [2] 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 [3] 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 [4], 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".

In [5], 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 [5] 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.5 illustrates the action of Ivermectin, as we can also find in Ref.2. "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" [2]. "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" [2,6].

[-] TrumpLyftAlles | 2 points | Jul 11 2020 01:02:20

In Ref.7 the authors report, as [2] and [5], 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 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 [7], 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" [8].

In [9], 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 [10], the dosage of Ivermectin is considered. "Caly et al. report a 5,000-fold reduction in SARSCoV-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 [10] are involved in trial [11].

Ref. 12 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 positivesense 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 [13], 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), Ddimer, 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 of DHF".

In [14], "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".

In [15], it is told that "Concerning the treatment outcome, adverse effect, and safety, IvermectinDoxycycline 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".

In [16], 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 [17], 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 [47]1, we find a Letter to the Editor of The Brazilian Journal of Infectious Diseases, entitled "Ivermectin: potential candidate for the treatment of Covid 19".

Let us conclude the review of scholar articles on the use of Ivermectin in Covid-19 patients with two preprint in MedRχiv.

In [18], 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 [18]: "To determine whether Ivermectin is associated with lower mortality rate in patients 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 [40], the results of the clinical trial (see the next section) https://ClinicalTrials.gov/show/NCT04343092. Posted July 08, 2020. Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial), by Faiq I. Gorial et al. , preprint in mderxiv.

[-] [deleted] | 2 points | Jul 11 2020 01:05:11

Here 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".

See also Refs.41-46 in SSRN and Researchgate

For what concerns ivermectin in general, I strongly suggest the reading of articles [19-21]. Let us add also [22]. 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 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" (this in the case of S stercoralis infection)

[A complete list of the 32 ivermectin vs covid-19 trials is provide, just titles, no value added. Omitted here, replaced with this link showing all the trials]

#News

News 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, 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."

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 - An important novelty is that today at San Raffaele testing of a new drug, Ivermectin, also begins. Archived http://archive.is/tqnX7

"Its use [Ivermectin] has been approved experimentally by AIFA, the Italian body of drug ". After the announcement of its efficacy in vitro," Now we are looking for clinical confirmation, yes it is a drug that has long been used against scabies, worms and other diseases produced by parasites whose specific mode of action has been clarified. Increases the concentration of chlorine inside cells that have specific receptors, including Covid 19. This fact leads to paralysis e then the death of the virus. Now the rapid clinical trial authorized in Italy remains, being one of the most affected countries ".

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, 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".

[-] TrumpLyftAlles | 2 points | Jul 11 2020 01:07:12

About the 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.18).

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/ - 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-mumbais-rajawadi-hospital-after-successful-ivermectin-treatment/ - 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".

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 available. 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 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

https://cnnespanol.cnn.com/ - Ivermectin, the weapon without scientific validation used in Bolivia to treat covid-19 - By Gloria Carrasco, CNN Posted at 16:23 ET (20:23 GMT) 29 mayo, 2020 Archived http://archive.is/17R1Y

"Bolivia included ivermectin in the list of essential drugs so that it can be used in the treatment of patients with covid-19. In the Beni department, in the north of the country, There is a campaign to distribute this medicine for free among the residents of the municipality. from Trinidad. "

https://cnnespanol.cnn.com/ - 17:17 ET(21:17 GMT) 10 Junio, 2020 - Peru gives impetus to hydroxychloroquine and ivermectin as a treatment for covid-19 - By Kiarinna Parisi Archived http://archive.is/w8KLw - Bolivia authorizes the use of ivermectin against covid-19 3:53

"The Ministry of Health of Peru (Minsa) gave impetus as treatment for the new coronavirus to two medicines that lack authorization by health authorities or consensus scientist on its efficacy and safety for covid-19 patients. ... For its part, ivermectin is a broad-spectrum antiparasitic agent approved by the Medicines Administration and United States food for certain uses in humans and animals, although prevention or Coronavirus treatment is not one of them. In early May, said authority discouraged its use associated with covid-19 after stating that more studies were needed in this regard. "

12/6/2020 https://www.eleconomistaamerica.pe/ "The San Juan de Lurigancho hospital began to prepare ivermectin to meet the existing demand for this drug by patients affected by COVID-19, which reach the hospital belonging to the Network Directorate Integrated Health (Diris) Lima Centro, informed the Ministry of Health." Archived http://archive.is/hak3F

https://exitosanoticias.pe/ - 13/6/2020 Dr. Fernández: “If more Peruvians took ivermectin, there would be fewer cases of COVID-19 ”- Using Ivermectin is like putting on a bulletproof vest against disease. In Peru, more than 1 million people consume it, and no one has died”, indicó. Archived http://archive.is/fusra

What does Ivermectin do in the body? "It prevents the virus from multiplying in cells. So the Ivermectin and Hydroxychloroquine work very well in initial cases or when just the disease begins ”.

https://www.marca.com/claro-mx/ - 11/6/2020 - Hydroxychloroquine and ivermectin: why do they carry the lead against coronavirus? "For his part, Marcelo Navajas, Minister of Health of Bolivia, issued a permit for the application of Ivermectin in humans to treat Covid-19 in said country, although they clarify that its use against the coronavirus is not endorsed by the Organization World Health." web.archive.org/web/20200614112908/https://www.marca.com/claromx/trending/2020/06/11/5ee18c6d268e3eaf4b8b45a9.html

https://www.connuestroperu.com/ - Miscellaneous June 12, 2020 - La Libertad will produce 150 thousand doses of ivermectin to fight the coronavirus - The Regional Government of La Libertad will produce 150 thousand doses of ivermectin to fight the coronavirus COVID-19 in mild patients . Archived http://archive.is/BKf8q https://www.connuestroperu.com/ - An interview with Dr. Antonio Camargo, June 02, 2020 - Archived http://archive.is/Cy8Wc. "You contracted the disease and were cured with ivermectin, could you tell us about your experience? I became infected in my work activities, caring for cancer patients. A patient who sought help and had a good time in our center infected two workers and the The cleaning worker infected me. The diagnosis of my infection was made on May 8 or 9. I had a terribly high viral load, to make a kind of surveillance pattern. I have a molecular biology laboratory and I remember the biologist told me My viral load was very high. Until that moment I felt nothing, just a dry throat, no cough or general discomfort or fever, but I knew that a "tsunami" was coming over me. There I decided to try what was testing other patients, I immediately took 60mg per day of ivermectin, accompanying with hydroxychloroquine: 200mg in the morning and 200mg at night, plus 200mg of zinc salts per day, which are high doses. treat me entonic coronicida. After 48 hours I had a control with PCR, a molecular test to control my viral load and there was no viral load in my pharynx, there were no viruses. "

In this interview, Dr. Camargo is reporting his experience and the use of ivermectin, hydroxychloroquine and zinc.

#The case of Iquitos (Peru)

This is a specific case which deserves a detailed discussion.

https://www.connuestroperu.com/ - 13/6/2020 - "The real COVID-19 Command of Iquitos: independent doctors managed to contain the scourge of the coronavirus, not the Minsa or Essalud" Archived http://archive.vn/ePtmg

[-] TrumpLyftAlles | 2 points | Jul 11 2020 01:13:02

"From the end of April to May, the daily scenes in the hospitals of Iquitos were of an avalanche of those infected with the coronavirus COVID-19, which exceeded their capacity and many patients could not be cared for, while others even died abroad. .. It is thanks to the independent doctors that Iquitos overcame the disaster caused by the pandemic, which is now controlled, because if it did not contain many patients in their homes with these successful treatments, all of them would have died. " Interview by Con Nuestro Perú with Dr. Sergio Bardon, "one of the independent doctors who participated in this fight and were the true COVID-19 Command in Iquitos."

Question: "From April to May, there is a growing number of doctors who use ivermectin successfully, there is a cure. To what do you attribute that this is not spread internationally and is preferred to drugs that have less effect? Answer;" Regarding ivermectin, what has been seen is that the viral load has decreased in many patients, that is, the amount of virus that a person has in the body, and therefore, will improve their condition. clinically and dramatically decrease the person's chances of complicating the viral infection. "

Dr. Bardon tells also: "The truth is that there are many doctors who are using ivermectin with great success. Of course, these drugs are more successful the sooner they are prescribed and the fewer symptoms the patient has, because when reaches a phase of acute complication, with significant dyspnea, there are many other things that are not necessarily acting viral load, because it is the inflammatory response that each patient has. Then ivermectin does not have much sense, that is why it is important not only to give it but to give it on time ... Indeed, the success that I have had with ivermectin is a lot. In general, from the third or fourth day already in the vast majority of patients No symptoms or signs of COVID-19 have been seen, and with regard to test negativization, it is also quickly obtained after one week .... I am treating all patients on an outpatient basis. Only one had to receive internally or, which was the first. From there they have all been followed on an outpatient basis, especially because I treat patients in Amazonas, Loreto, in places where they do not even have the possibility of going to a hospital and we are basically managing it with the association of ivermectin - azithromycin, and so far all have been successful. "

Then, in Iquitos the ivermectin was used. Iquitos is the capital city 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 [24], it was told that the health system in this town was subjected to a very high stress for Covid19. "The first COVID-19 case in the Peruvian Amazon, detected on March 17, seemed to be a oneoff — 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 [24] 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-peruvianamazon-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? - 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 - "In Iquitos they have been applying Ivermectin for veterinary use with good results compared to Covid19 ". Archived http://archive.is/yx24r

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 soles2 , 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 injection is being applied to people with mild symptoms of Covid 19, the care will be totally for free.

#A drug for humans

About the concerns of using a drug involved in veterinary use, an answer is the following. "Ivermectin was created for the treatment of humans" - Trujillo doctor Gustavo Elera has stopped the coronavirus in about 1,200 patients in Chanchamayo with this drug, widely used in veterinary medicine. " http://www.laindustria.pe/nota/16073-la-ivermectina-fue-creada-para-el-tratamiento-de-humanos - dated 7 June 2020 - Archived http://archive.is/beTgM

"From April to date, the doctor Gustavo Elera Arévalo, not Trujillo himself, has treated 1,200 patients, all of them affected by the coronavirus, in La Merced, Chanchamayo, Junín with excellent results." In this article, the reporter asks Dr. Elera about the difference between Ivermectin for human and veterinary use. Question: "On the market we find Ivermectin for human and animal use. Human use has been scarce and the few that are found have a very high cost. So, can you use the veterinary medicine?" Answer: "Sure. It is not toxic. We have used the one for veterinary use for the La Merced prison (Chanchamayo), for the National Police, for all the patients we are seeing without any problem and we are going to use it in the sweep that We will do in some other sectors of Chanchamayo itself. The difference between Ivermectin for human use and veterinary use is that for human use is Ivermectin plus water and Sorbitol, which is a flavoring that makes it sweet, and the one for veterinary use is Ivermectin plus water, period. "

[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:18:29

In the market we find Ivermectin for human and veterinary use. The formulations for human use are in short supply and at a very high cost. "So, can you use veterinary medicine?" Elera's answer: "Sure. It is not toxic. We have used the one for veterinary use for the ... The difference between Ivermectin for human use and that 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.

Of course, 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. "Veterinary doctor Eleazar Vargas pointed out that the ivermectin that has been used for humans differs in concentration from that used for animals". 18 Junio, 2020 - http://archive.is/1qN3N

Dr. Eleazar Vergas is dean of the Veterinary Medical College. Let us report some sentences from this article “There is only one ivermectin, which is dedicated to animals or humans is already a matter of concentration. Although I think they only use it orally for humans, ”the expert told Exitosa. It is also told, "On the other hand, the dean of the Veterinary Medical College called on physicians to respect the veterinary profession, after some derogatory comments were generated by some of them regarding veterinarians' views on * ivermectin *: "I think it is an unwelcome contrast, this is not the time to say I am more or I am less. I have heard that they even speak of the vet in a derogatory way, it should not be like that. We are health professionals."

We can find further information about the use of ivermectin in Peru in the recent https://elcomercio.pe/tecnologia/cienciasivermectin-gustavo-elera-ivermectin-el-medico-que-seha-convertido-en-el-referente-nacional-de-una-campana-anticovid-19-que-carece-de-base-cientifica-noticia/ - 26 June 2020. Ivermectin - The face of a campaign against COVID-19 that is growing in Peru but has no scientific basis - Doctor Gustavo Elera encourages the use of ivermectin in various regions of the country with the support of mayors. Despite the opinion of experts, he claims to have sufficient evidence for it ". 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 "In various regional media, the doctor [Elera] has defended the use of veterinary ivermectin instead of the one made for humans, arguing that the former is much cheaper. He has also assured that" the of veterinary use is Ivermectin plus water and period.

And a link is given: https://elcomercio.pe/tecnologia/ciencias/coronavirus-ivermectin-covid-19-en-ucayali-autoridades-reparten-ivermectin-para-animales-para-tratar-pacientes-con-coronavirusnoticia/?ref=ecr/ - dated 26 May 2020, where it is told that "Two regional councilors, one of them from the Alliance for Progress party, publicize their initiative as "a philanthropic act." However, experts emphasize that veterinary medicine can be harmful in humans.". The article has the title: COVID-19 | Authorities distribute ivermectin to cows to treat patients with coronavirus in Ucayali". Veterinary medicine is a branch of medicine, working with drugs, like the ivermectin, 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" [25].

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.

“[The animal presentation] could have ivermectin as the active ingredient, but what else it has is unknown. Those other components are those that can produce unwanted effects ”, explains Alfonso Zavaleta, professor of Pharmacy and Biochemistry at the Universidad Peruana Cayetano Heredia (UPCH). ... The mode of application in humans is oral, while in animals it is intramuscular. ... Ricardo Grandez, professor at the UPCH Faculty of Veterinary Medicine and Animal Husbandry, warns that if this drug is administered subcutaneously and intramuscularly and "is applied improperly, it can cause necrosis in the area of application." “The injectable presentation [used in animals] is long-lasting, it has substances that slowly release the active ingredient. Some of these products could generate reactions in some individuals or in all individuals. "

Actually, for animals too, it is necessary to be careful and in fact, it is told "Dosage and route of administration: ... Subcutaneous route (S.C.) only"., as at the web page of this company https://www.vecol.com.co/productos/veterinaria/antiparasitariosivermectin-1,which is archived http://archive.is/YAEVk . See also https://www.ema.europa.eu/en/documents/referral/bovimectininjection-article-33-referral-annex-i-ii-iii_it.pdf . For veterinary use, subcutaneous injections3 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 [26,27].

#Stabilized aqueous formulation

Gustavo Elera tells that the drug for veterinary use is "Ivermectin more water and point”. 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.28, 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 [29], and pain and inflammation at the injection site were commonly observed side effects of commercial ivermectin preparations [30]. "The commercially available ivermectin preparations employ different vehicles that help in stabilizing the compound".

Table 1 of [28] 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 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 [28], 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" [31].

[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:24:22

#"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 [32], it is told that "There are no parenteral antihelminthic4 drugs licensed for use in humans. [The authors of [32]] 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 [33], 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 [27], 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" ([34], 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?

#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.

"A Peruvian evangelical group injects a veterinary drug into thousands of people for covid-19." This is the title of an article in El Pais that started a sequence of news. "In Nauta, at least 5,000 people have received it [ivermectin]", says Leonardo Tello, director of Radio Ucamara, the city's main radio station located two hours from the region's capital, 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 says that many people felt the acceleration of the heart after receiving the injection." The side effect has been horrifying, "he says. The director of Radio Ucamara explains that some evangelical pastors from Loreto have linked the new coronavirus with the devil and the end of the world, offering those injections “as a salvation.” El Pais continues explaining that "In the community of Cuninico, where a large part of the population had symptoms of covid-19, the health module technician ... told the volunteers of the so-called Evangelical Missions of the Amazon, who no longer needed the “vaccine” because the majority of people were taking care of themselves with traditional medicine, with plants. However, those sent by the evangelical group decided to administer the veterinary ivermectin. "The volunteers' explanation was clear and direct that it is approved by law, and that it is an animal treatment that gives positive results as a vaccine," said Cuninico's apu - indigenous chief - Wadson Trujillo Acosta. They are doing it nationally and also in Nauta, and they warned of side effects such as diarrhea. Some people did have this reaction, "he described."

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-amazonevangelicals-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.

In actuality, the radio guy said that the side-effects were diarrhea, increased heart rate, and that's all. There are at least three articles in the sub quoting the guy. - TLA

#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

"Perhaps Peru is the epicenter 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 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". The titles of some of these documents are given by the site. Gustavo A. Aguirre-Chang is the author of the document entitled "INCLUSION OF Ivermectin IN THE FIRST THERAPEUTIC LINE OF ACTION FOR COVID-19. A very significant decrease in the Mortality Rate is reported with its use. Lima, Peru. May 2, 2020". Available at the link https://www.reddit.com/r/ivermectin/comments/gqm6k7/inclusion_of_ivermectin_in_the_first_therapeutic/ - http://archive.is/x12Co .

The link from the article is broken and searching for the title didn't produce any hit on the original domain (i.e. the domain of the article's broken link) -- but it did turn up hits on this sub, so I substituted one of those. - TLA

The author5 is telling that "For his part, in the Dominican Republic, the Pulmonologist J. Tavares reports that he is treating 247 patients with Ivermectin with a favorable response in all cases and has not reported any fatal cases. Similarly, locally, Although to date there are not many documented cases yet, the case fatality rate has been 0% and it is also observed that in 100% of the cases treated with Ivermectin there is an improvement in the disease and resolution of fever within 48 hours of starting treatment. " Aguirre-Chang is detailing of 82 cases in Peru6.

[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:28:42

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%."

This information actually comes from this post to this sub quoting information Dr. Aquirre posted to quora. Still, it's nice to be a source, apparently, even if the details are slightly off. :) -TLA

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".

"Prominent researchers and industry observers were obviously skeptical and downplayed the Monash findings7 , arguing that studies in humans weren’t feasible due to dosage and other factors.

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 epicenter 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 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".

Further news (until 10 July) Trafficking drugs. SANTA CRUZ -Arrestan the personas for ivermectin with sextuplicate price - 29 June 2020 - http://archive.vn/GWW7f and also Ivermectin trafficking - "Two men are caught with 250 boxes of ivermectin smuggled from Bolivia in MT [Mato Grosso], medicine used against Covid-19 - In addition to ivermectin, they also smuggled 25 boxes of levofloxacin hemihydrate, nine boxes of Paracetamol and 14 boxes of Ibuprofen. the merchandise is valued at R $ 8 thousand. - 29/06/2020 10h51 - http://archive.vn/K4pLG

The Gorvernor of Mato Grosso - “I didn't take chloroquine. Nothing against, but ... ”. The governor said he used two pills of Ivermectin for one day. The remedy is an anthelmintic (vermifuge), which in an in vitro study would have demonstrated the ability to reduce the duplication of the virus and prevent it from entering the cells. However, little evidence demonstrates its effectiveness ". 09/06/2020 - http://archive.vn/sHWX5

"Peruvian doctors ask to stop the use of hydroxychloroquine e ivermectin in COVID19 patients" - 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/ archived http://archive.vn/YbsuR - "The docto rs ... were concerned about the use of hydroxychloroquine and ivermectin promoted by the health authorities in the country as a treatment for COVID-19."

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".

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 Peruvian Ministry of Health also promoted hydroxychloroquine has an effective treatment".

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 - "A group of 478 doctors from the Federal District elaborates a protocol for early treatment of Covid-19 Document with suggestion of medications was delivered to the Health Department and includes hydroxychloroquine and ivermectin" - https://www.metropoles.com/colunas-blogs/grande-angular/grupo-de-478-medicos-do-df-elabora-protocolo-para-tratamento-precoce-da-covid-19 - "A group of 478 doctors from the public and private network of the Federal District met to elaborate and propose an early treatment protocol for patients infected with the new coronavirus. In the list of drugs to be offered to patients is hydroxychloroquine, in addition to the vermifuge ivermectin and the antibiotic azithromycin. ... “We have medications that are available, they are low cost, low toxicity and can be prescribed by doctors in the first stage of Covid-19 to decrease viral replication. Of course, we would all like to work based on solid scientific studies. But we live in an atypical, war situation The new the coronavirus is not in the package insert, because it did not exist when the drugs were created ”, explains the otorhinolaryngologist Carine Petry, one of the members of the group.

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 antiviral 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".

[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:33:53

#SSRN or Antiviral Research

As we have previously seen, a working paper was published in SSRN and then retracted. For this reason, I have not discussed it above. However it is time to give some information. In Google Scholar "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 …". The paper was withdrawn from SSRN by the authors. The reason to consider it is in the following news.

5 July 2020 - "San Marcos: treatment with ivermectin has a lower case fatality rate" - https://www.radionacional.com.pe/noticias/locales/san-marcos-tratamiento-con-ivermectina-tiene-menos-tasa-de-letalidad Fatality Rate - The fatality rate in patients who used ivermectin in their covid-19 treatment was 6.1 times lower compared to patients who did not use it, according to a study by the doctor graduated from the 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 - "Ivermectin and COVID-19: the errors and lies behind a viral “study” of dubious quality "- 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, I suppose it is the same of that at the link in the note8 ). The elcomercio.pe tells the research "it had been published in Antiviral Research. El Comercio found that the study does not appear in this international medical journal". In the document (see the footnote), Dr. Aguirre Chang does not tell that his work was published in the Antiviral Research journal. This was a mistake in El Comercio. The document is a working paper. In any case, let us stress that the paper published in the Antiviral Research journal is Ref.2. In Aguirre's working paper, there is a mistake in abstract and text. He tells that the document in SSRN has been placed on the web site of Antiviral Research. This mistake raised confusion, enhanced in the news by elcormercio. It seems to me that a document to consider is [43]. RESULTS: 33 adult patients with Persistent Symptoms of COVID-19 were treated with Ivermectin. In 97% of the 33 patients treated with Ivermectin, clinical improvement was found after the 2 doses of Ivermectin. The clinical improvement was total in 87.9% of the patients after the 2nd dose of Ivermectin. In 12.1% of the patients, it was required to give more days of treatment with Ivermectin, but this achieved clinical improvement and remission of symptoms in 100% of the cases. CONCLUSION: The result of the present study finds effectiveness of the treatment with Ivermectin of the patients with Persistent Symptoms of COVID-19, observing a clinical improvement in 100% of the cases "". 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 then the news previously mentioned on him) and from all the other doctors engaged in the Health Movement.

#Making ivermectin for oral use (6mg/mL)

As we have seen before, 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 selfinjection 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-essaludmoyobamba-comenzo-a-producir-ivermectin-con-capacidad-de-20-mil-dosis-mensuales-nnppnoticia/ , we read that ivermectin for oral use is produced in a local hospital. "Excellent news for the San Martín region made EsSalud-Moyobamba known, after announcing that it has been producing ivermectin for the treatment of patients with COVID-19, in charge of the Pharmacotechnics area of Hospital II-1 Alto Mayo that It is capable of preparing 20 thousand monthly doses. ... Likewise, the composition of ivermectin includes ethyl alcohol, propylene glycol, sorbitol and ivermectin for medical use (solid), and will be supplied under medical prescription ". 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

[IVERTODO Insert chart]

#Data

As we can appreciate in the news from Peru - and South-America, in general - a large use of ivermectin is and will be made for Covid-19. It is therefore clear that an effectiveness of the drug can be easily evidenced by the numbers about new, active cases and victims in the country. From the web page https://www.worldometers.info/coronavirus/country/peru it seems that the number of daily victims of the virus is slowly reducing. In the plots given below, a proposed by the www.worldometers.info, it is reasonable to imagine that the curves will decrease in the next weeks. The behaviour of decreases will be influenced by any effectiveness of the drug.

[IVERTOTO Insert charts of daily new cases and active cases in Peru]

Courtesy: Data at the end of June https://www.worldometers.info/coronavirus/country/peru

On 10 July, the curve of active cases decreased is below 100000 cases, specifically 97332.

#Acknowledgement

I would like to offer my special thanks to Dr. Rocio Ferrel for her precious support on literature and news concerning Ivermectin.

#Appendix

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/covid19/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 [35], 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)".

[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:35:13

In [36], 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 synthesis in vitro, (Refs. 51 , 52 of [36]) 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. [37]: "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 [38,39].

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[-] TrumpLyftAlles | 1 points | Jul 11 2020 01:35:28

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[47] Gupta, D., Sahoo, A. K., & Singh, A. (2020). Ivermectin: potential candidate for the treatment of Covid 19. The Brazilian Journal of Infectious Diseases. Braz J Infect Dis. 2020 Jun 28 - doi: 10.1016/j.bjid.2020.06.002 [Epub ahead of print] - PMCID: PMC7321032 - PMID: 32615072

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