Third part of a timeline of ivermectin-related events in theCOVID-19 pandemic
See Part 1 and Part 2
Mika Turkia M.Sc.
September 30, 2021
This review presents a third part extending two previous parts of a timeline describing ivermectin-related events in the COVID-19 pandemic, with this third part covering a period from July 2021 to September 2021.
Among the most notable developments during the period were allegations that a clinical trial about prophylaxis and late treatment of COVID-19 with ivermectin by Elgazzar et al. carried out in Egypt in mid-2020was fraudulent, with some of the introduction plagiarized and the patient data claimed to appear fabricated.
The government of Egypt initiated an investigation on the issue, the results of which were not available bythe end of the period.
Ivermectin skeptics noted that the retraction of the Elgazzar et al. trial, along with suspicions about failed randomization in another trial by Niaee et al., seemed to invalidate the various meta-analyses which had included these trials. Ivermectin proponents argued that the retraction did not aﬀect the conclusions of their meta-analyses. Later, the validity of an Argentinian prophylaxis trial by Carvallo et al. was questioned; as an observational trial it had not been included in the meta-analyses.
Among new trial results were the results of ’Together’ trial led by a Canadian university but carried out in Brazil. The primary endpoint was extended emergency room observation or hospitalization, and the secondary endpoint was mortality. Fluvoxamine produced a statistically signiﬁcant result for the ﬁrst endpoint but not for the second. In 677 treated patients vs 678 controls ivermectin indicated some risk reduction but the diﬀerences were not statistically signiﬁcant. One of the authors concluded that ivermectin had ’noeﬀect whatsoever’ on their endpoints. On the other hand, a intervention program in La Pampa province of Argentina with 3,269 treated and 18,149 untreated indicated mortality rates of 1.5% vs 2.1% (p=0.029),and in subjects over 40 years 2.7% vs 4.1% (p=0.005). A Cochrane meta-analysis concluded that all aspects regarding ivermectin’s eﬃcacy for either treatment or prophylaxis were currently unknown.
After a 24-fold increase in ivermectin prescriptions from US pharmacies compared to the pre-pandemic baseline, US Food and Drug Administration (FDA), American Medical Association, American Pharmacists Association and American Society of Health-System Pharmacists campaigned against ivermectin, calling for‘an immediate end’ to prescribing, dispensing and using it. However, this campaigning also resulted in an increased public awareness of ivermectin.
A prominent social media ﬁgure with over ten million followers revealed that he had been prescribed ivermectin for COVID-19. The fact was subsequently propagated internationally by the news media which represented ivermectin as a dangerous ‘horse dewormer’. Several international news outlets published a false story about emergency rooms in Oklahoma being full of people having overdosed ivermectin, blocking out other patients including gunshot victims.
A Japanese doctor who had treated 500 patients with ivermectin reported having received death threats after telling about his methods on a television program. A group of British scientists which had published a meta-analysis about ivermectin reported having received death threats after questioning the eﬃcacy of ivermectin. An ivermectin discussion forum was ﬂooded with pornographic images and incoherent babbling.
A hospital was harassed for not administering ivermectin.
An Indian physician claimed that due to the World Health Organization’s opposition to ivermectin, India’s second wave had been countered by an almost nationwide covert use of early treatment protocols including ivermectin. Another physician reported that in one city in Amazonas, Brazil, a mass distribution of ivermectin had resulted in the city having no hospitalized COVID-19 patients during the surge of the gamma variant in the ﬁrst half of 2021.
Frontline COVID-19 Critical Care Alliance (FLCCC) faced criticism for its ivermectin advocacy and communication style. With regard to treatment protocols, the addition of dual anti-androgen therapy to FLCCC’sMATH+ hospital treatment protocol was said to have restored the protocol’s eﬃcacy against the delta variant in intensive care unit patients. FLCCC also published a scoping review of the pathophysiology ofCOVID-19, emphasizing the role of platelet activation with the release of serotonin and the activation and degranulation of mast cells contributing to the hyper-inﬂammatory state.
In an overview, the period from April 2020 to March 2021 could be characterized as a period of argumentation and attempted rationality, the period from April 2021 to June 2021 as a period of emotion and campaigning,and the period from July 2021 to September 2021 as a period of chaos.
Current best practices for meta-analyses were found to be unsound. A new approach based on individual patient data analysis was proposed.
The period covering the ﬁrst part of the timeline from April 2020 to March 2021  could be characterized as a period of research, argumentation and rationality. During the period, smaller-scale research and experimentation of ivermectin for COVID-19 was pursued and eventually, alliances and groups of clinicians and researchers were formed to promote combination treatment protocols that included ivermectin. However, at the end of the period, ﬁrst the European Medicine Agency (EMA) and second the World Health Organization(WHO) advised against the use of ivermectin except in clinical trials.
The second period from April 2021 to June 2021  could be characterized as a period of emotion and campaigning. During the period, a failure of the approach based on argumentation led to a disillusionment of clinicians and researchers in favor of ivermectin treatments and stopped communication between the proponents and administrative agencies. Instead, ivermectin proponents turned directly to the public and the clinicians. The analysis related to the second part of the timeline focused on possible structural corruption and the role of the WHO.
The third period from July 2021 to September 2021 covered in this paper might best be characterized as a period of chaos, initiated by accusations of plagiarism and data fabrication in one of the early ivermectin trials . As the trial was included in published meta-analyses of ivermectin’s eﬃcacy [4,5,6], the allegations undermined the believability of these meta-analyses, although the authors of the meta-analyses at ﬁrst stated that the exclusion did not essentially change the results of the analyses. Later, one of the groups diverged from this view.
The history, indications and safety of ivermectin have been described in the previous parts. Some events preceding July 2021 not included in the previous parts of the timeline have been included.
On March 25, Waltner-Toews et al. wrote that COVID-19 requires a new approach to science . They referred to ‘post-normal science’ (PNS) developed in the 1990s by Silvio Funtowicz and Jerome R. Ravetz which represented a novel approach for the use of science on issues where ‘facts are uncertain, values in dispute, stakes high and decisions urgent’ . As an example, PNS recommended that models to predict and control the future should be replaced by models to map our ignorance about the future; it also stressed the importance of trust, participation and transparency, all of which had been lacking during the COVID-19pandemic. Waltner-Toews et al. wrote that ‘everywhere, we are seeing a total breakdown of the epistemic consensus required to make normal science “work”. This is happening not only in the ﬁelds you might expect– behavioral psychology, sociology, and ethics – but also in virology, genetics, and epidemiology. In other words, when “applied scientists” and “professional consultants” are no longer in their comfort zones but ﬁnd themselves in a post-normal context, ﬁtness for purpose changes meaning. And even in established ﬁelds, disagreements can’t be hidden (or consensus enforced) from broad audiences: are the present draconian measures justiﬁed or not? More data (even “reliable data”) and better predictive models cannot resolve the“distribution of sacriﬁce” which involves, among other things, the arbitration of dilemmas that appear at every scale. Hiding behind some general notion of science or the “lack of data” – as if data had the power to resolve these dilemmas – is feckless, feeble and confused’.
On November 29, an article by Cherkes et al. in the clinical practice guidelines and recommendations section of an Ukrainian journal Proceedings of the Shevchenko Scientiﬁc Society – Medical Sciences gave a detailed description of FLCCC’s MATH+ hospital treatment protocol .
On April 14, an article by Seet et al. described an open-label randomized trial (n=3,037) describing a 42-day prophylaxis regimen with four diﬀerent medications, one of which was povidone iodine throat spray(n=735), compared to 500 mg per day of oral vitamin C (n=619), indicated 44.7% lower risk of severe disease (5.7% vs 10.3%, RR 0.55, p=0.05) and 31.1% lower risk of infection (46.0% vs 70.0%, RR 0.69,p=0.01) [10,11]. A single 12 mg dose of ivermectin (n=617) did not produce a statistically signiﬁcant diﬀerence. Hydroxychloroquine produced a slightly smaller risk reduction than povidone iodine.
On May 11, two Norwegian doctors presented data on ivermectin trials to the Norwegian government .
On May 26, an investigational monoclonal antibody for mild to moderate COVID-19, sotrovimab, was issued an emergency use authorization by the US Food and Drug Administration (FDA). Sotrovimab was to be administered as a single intravenous infusion of 500 mg over 30 minutes within 10 days of symptom onset .
The wholesale price of a single dose was USD 2,100 .
On May 28, Bloomberg Law discussed YouTube’s censorship practices . YouTube chief executive oﬃcer Susan Wojcicki commented that ‘the complex nature of misinformation online presents a number of challenges for platforms such as YouTube and I welcome your suggestions as to what we can do better’.
On June 1, a commentary by Chosidow et al. asked whether ivermectin would be a potential treatment forCOVID-19 .
On June 4, an article by Payne et al. about evidence-based approach to early outpatient treatment considered zinc gluconate, melatonin and vitamin D feasible options but repeated the usual objections to ivermectin.
On June 7, an article by Sajidah et al. discussed the host nuclear transport machinery in detail .
On June 10, Kumar et al. discussed the role of vitamins and minerals as immunity boosters in COVID-19, pointing out for example the protective roles of calcium, magnesium, copper, iodine, selenium, manganese,cobalt and sulfur, and the possibly harmful eﬀect of iron .
On June 14, an article by Duru et al. described an in silico study suggesting that ivermectin bound well toSARS-CoV-2 spike glycoprotein .
On June 17, an article by Yanagida et al. concluded that ivermectin had low proarrhythmic risk .
On June 18, an article by Mart´ınez investigated the antioxidant properties of several pharmaceuticals, positing the idea that oxide reduction balance might help explain the toxicity or eﬃcacy of these drugs, and noting that ivermectin and molnupiravir, two powerful COVID-19 drugs, were not good electron acceptors,and the fact that they were not as eﬀective oxidants as other studied molecules might be an advantage .
On June 18, a commentary by Taibbi discussed politicization and censorship of ivermectin in the US [23,24].
On June 18, a Norwegian newspaper Aftenposten interviewed two Norwegian proponents of FLCCC protocols, one of whom was FLCCC founding member Eivind Hustad Vinjevoll  and the other Anders Bugge.
The Norwegian Medicines Agency remained unconvinced, stating that it was not their task to assess unapproved treatments: they only followed the recommendations of US National Institutes of Health and the World Health Organization.
On June 21, referring to lack of evidence and low quality of trials, eleven Norwegian senior physicians disagreed with Vinjevoll’s and Bugge’s views .
On June 22, Huang et al. summarized recent advances in the exploration of ivermectin’s anticancer properties .
On June 27, Salvador et al. published a protocol of a prospective observational study aiming to evaluate the eﬀectiveness and safety of a single-dose ivermectin for treatment of uncomplicated strongyloidiasis in immunosuppressed patients .
On June 28, Bugge replied to the Norwegian senior physicians .
On June 28, an article by Roman et al. presented a meta-analysis of ten randomized controlled trials(RCTs) including 1,173 patients with mild or moderate disease . The authors wrote that in comparison to standard of care or placebo, ivermectin did not reduce all-cause mortality, length of stay or viral clearance.
They concluded that ivermectin was not a viable option to treat COVID-19 patients. The article was based on a previous preprint [31,32]. The CovidAnalysis group noted that in addition to numerous uncorrected errors,the preprint and the PDF of the article stated that the authors had no conﬂicts of interest, yet Pasupuleti’saﬃliation listed in the abstract on the journal’s website was a company delivering brand and portfolio commercial strategy for biotech and pharma, working with 24 of the top 25 pharmaceutical companies as well as hundreds of biotechs globally [33,34]. The company also stated that they were working withthe European Federation of Pharmaceutical Industries (EFPIA) to support their activities, and that the company’s regulatory consultancy practice in the US was preparing a number of emergency use authorizations to the FDA .
On June 28, an article by Patterson et al. presented a model for predicting COVID-19 severity and chronicity . A score measuring severity of COVID-19 was deﬁned as (IL-6 + sCD40L / 1000 + VEGF / 10 + 10 * IL-10) / (IL-2 + IL-8). A score measuring chronicity (long haul symptoms) was deﬁned as (IFN-γ+ IL-2) / CCL4-MIP-1β. CCL4 (chemokine ligands 4), also called MIP-1β(macrophage inﬂammatory protein-1β),was related to the C-C chemokine receptor type 5 (CCR5) pathway. About VEGF, see also [37,38,39,40].
On June 30, Thailand’s FDA and Chiang Mai University’s faculty of pharmacy warned against using ivermectin for COVID-19 .
On June 30, an article by Nippes et al. reviewed research on the presence of chloroquine, hydroxychloroquine, azithromycin, ivermectin, dexamethasone, remdesivir, favipiravir and some HIV antivirals in the environment, and presented treatment technologies for each drug .
On June 30, Syed interviewed FLCCC’s Marik about treatments and the origin of SARS-CoV-2 .
On July 1, HART group consisting of UK doctors compared adverse events reported to the WHO of ivermectin (20 deaths and 5,484 adverse events since 1992), remdesivir (534 deaths and 6,707 adverse events since 2020) and COVID-19 vaccines (6,667 deaths and 1,198,200 adverse events since 2020) . They also suggested that some of the ongoing studies were designed to fail and actually aimed at stalling the adoption of ivermectin.
On July 1, Vice magazine wrote about ivermectin advocates, saying that ‘proponents of a dubious COVID19 cure have signaled they’re ready for a long ﬁght against what they see as censorship in medicine and media’ .
On July 2, an article by Vallejos et al. described a low dose RCT with 501 relatively low-risk outpatients in Argentina which did not produce statistically signiﬁcant results (NCT04529525) [46,47].
On July 2, an article by Adegboro et al. reviewed the antiviral eﬀects of ivermectin .
On July 2, a Twitter post reported that a video featuring Nobel prize winner Satoshi ¯Omura discussing Japanese ivermectin emergency use authorization bill had been removed by YouTube for violating their terms of service .
On July 2, a blog post by Crawford investigated the details and the background of the meta-analysis by Roman et al., noting that the meta-analysis came at a politically contentious moment, the language and behavior appeared political, the work was error-laden, took research out of its true context, used numbers that didn’t seem to come from the actual studies, chose papers testing ivermectin under the least favorable circumstances, gave unexplained and inappropriate weights to the small amount of data that stood as outliers to the bigger picture, and extracted an unfavorable conclusion from a massive average mortality reduction that did not quite reach statistical signiﬁcance while consistently complaining about the low quality of evidence represented by the studies . Crawford asked whether these were ‘just mistakes’, adding that ‘a medical journal published all this – just in time to push back the Lawrie case. Think on all that for a moment’.
On July 3, an open letter signed by 43 researchers and clinicians requested retraction of the meta-analysis by Roman et al. [51,52].
On July 6, an article by Hill et al. (submitted on January 20) presented a meta-analysis including eleven RCTs of moderate/severe infection . The analysis indicated 56% reduction in mortality (3% vs 9%, RR0.44, 95% CI 0.25-0.77, p=0.004), favorable clinical recovery and reduced hospitalization. In contrast to the preprint stating that ivermectin should be validated in larger studies before the results are suﬃcient for review by regulatory authorities , the published version said that a network of large clinical trials was in progress to validate the results seen to date.
On July 6, a TrialSite news report suggested that the WHO might have been attempting to limit the use of ivermectin to neglected tropical diseases only [54,55,56]. The report also discussed the apparent lack of objectivity of Wikipedia, noting that it had, among other omissions, mentioned the rejection of FLCCC’s review by Frontiers of Pharmacology but failed to mention that it had later been published in the American Journal of Therapeutics, failed to mention the meta-analysis by the BIRD group, and failed to mention USNIH’s transitioning to a neutral stance on ivermectin. The report asked why any positive aspects would be omitted unless there was an explicit goal to completely discredit this possible therapeutic option and researchers looking into the matter.
On July 6, Yahoo News UK published a news story featuring ivermectin in a positive light .
On July 6, WHO announced that it had updated its patient care guidelines to include interleukin-6 receptor blockers tocilizumab (by Roche) and sarilumab (by Regeneron Pharmaceuticals and Sanoﬁ) . The strong recommendation was based on ﬁndings from a prospective and a living network meta-analysis including data(also prepublication data) from over 10,000 patients enrolled in 27 clinical trials. The meta-analyses were said to show that in severely or critically ill patients these drugs reduced the odds of death by 13% and the odds of mechanical ventilation by 28% compared to standard of care, with high certainty of evidence . WHO said tocilizumab and sarilumab were the ﬁrst drugs found to be eﬀective against COVID-19 since corticosteroids were recommended in September 2020 . WHO director-general Tedros Adhanom Ghebreyesus said, however, that the drugs would remain inaccessible to most, and called on manufacturers to reduce prices and make supplies available to low-and middle-income countries. Ghebreyesus also encouraged companies to agree to transparent, non-exclusive voluntary licensing agreements using WHO’s Covid-19 Technology Access Pool (C-TAP) platform and the Medicines Patent Pool, or to waive exclusivity rights. Rochwerg et al. noted that compared with other treatments IL-6 receptor blockers were expensive but the the recommendation did not take account of cost eﬀectiveness . They also acknowledged that access to these drugs was challenging in many parts of the world and that the recommendation could exacerbate health inequity. However, the strong recommendation aimed at providing a stimulus to improve global access to these treatments.
On July 6, an article by WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) WorkingGroup presented a meta-analysis on the eﬃcacy of tocilizumab and sarilumab . Absolute mortality risk was 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for standard of care or placebo, with especially sarilumab showing very low eﬃcacy. Regarding conﬂicts of interests, one of the authors reported being involved with two patents owned by Genentech/Roche, one on treating COVID-19with an IL-6 antagonist, and another for tocilizumab and remdesivir combination therapy for COVID-19pneumonia. Two other authors reported being co-inventors of a ﬁled patent covering the use of low-dose tocilizumab for treatment of viral infections. Nine other authors also reported associations with Roche.
Seven authors reported associations with Sanoﬁ. Three reported being employees of and owning stock in Regeneron, and two reported other associations with it. Also associations with, for example, Merck Sharp and Dohme, Gilead Sciences, ViiV Healthcare, Janssen, Cilag, Thera technologies, Lilly, Biohope, Gebro, Bristo lMyers Squibb, Abbvie, Pﬁzer, Novartis, PharmaMar, GlaxoSmithKline, Boehringer Ingelheim, Celgene,Alexion, Inatherys, AB Science, Argenx, Oncoarendi, Biogen, Ose Pharmaceutical, Shionogi, Genetech, EliLilly, Swedish Orphan Biovitrum AB, Sanoﬁ Genzyme, Aspen Pharmacare, Crist´alia and AM Pharma were reported.
On July 6, a press release by M´edecins Sans Fronti`eres (MSF) noted that the Swiss pharmaceutical company Roche continued to have de facto market exclusivity and tocilizumab was likely to remain unaﬀordable and inaccessible for most of the world . MSF wrote that Roche had kept the price of tocilizumab very high in most countries (USD 410 in Australia, USD 646 in India and USD 3,625 in the US per dose of 600mg for COVID-19, while the manufacturing cost was estimated to be around USD 60).
On July 6, an article by Malin et al. presented a key summary of German national treatment guidance for COVID-19 inpatients . The guideline recommended corticosteroids, prophylactic anti-coagulation, and optionally tocilizumab. Convalescent plasma, azithromycin, ivermectin and vitamin D3were recommended against. With regard to ivermectin, it was said that achievable tissue concentrations seemed to be far below the half maximal inhibitory concentration in vitro, that in February 2021 only one peer-reviewed RCT with 72 patients was available for consideration, and that the numerous preprints did not report clinically relevant endpoints or presented with signiﬁcant methodological issues and a high risk of bias.
On July 6, a commentator asked why WHO targeted IL-6 instead of going upstream to block NF-kB  which in turn inhibits IL-6 (ivermectin is an NF-kB antagonist ) [65,66].
On July 6, the US president Biden proposed the creation of the Advanced Research Projects Agency for Health (ARPA-H), a new organization under the NIH, aimed at facilitating and accelerating more innovation and breakthroughs in fundamental biomedical and health research .
On July 6, an article by Margolin et al. described a small controlled trial (n=113) that suggested beneﬁts from supplementation with zinc, zinc ionophores quina plant bark extract and quercetin, vitamins C, D3and E, and L-lysine .
On July 7, an article by Cadegiani et al. about an open-label observational prospective outpatient study indicated 98.0% lower risk of hospitalization (0% vs 19.7%, RR 0.02, p<0.001) and 94.2% lower risk of ventilation (0% vs 6.6%, RR 0.06, p=0.005) [69,70,71]. The authors said treatments showed overwhelming improvements; therefore, it had become ethically questionable to conduct further studies employing full placebo arms in early COVID-19.
On July 7, a preprint by Hazan et al. described a retrospective late treatment study with 24 outpatients and a synthetic control arm calculated from the US Centers for Disease Control and Prevention (CDC)database . The study used a combination therapy protocol with ivermectin, doxycycline, zinc, vitaminD and vitamin C, resulting in 100% survival and cure in unselected ambulatory ‘moderate to severely’ illCOVID-19 outpatients, with some initially presenting with SpO2values as low as 73% and 77%. Despite a symptom to treatment delay of over nine days, mean SpO2values rose from 86.5 to 93.1 in the ﬁrst 24 hours.
On July 8, an article by Muthusamy et al. described an in silico study identifying 32 anti-parasitic compounds eﬀectively inhibiting the receptor binding domain of the SARS-CoV-2 spike protein . The most eﬀective compounds, in a descending order, were selamectin, ivermectin, artefenomel, moxidectin, posaconazole, imidocarb, piperaquine, cepharantine, betulinic acid and atovaquone.
On July 9, Cameron et al. proposed a two-axis model to describe variability in decision-making among critical care physicians . The authors emphasized the necessity for a better understanding of the root causes of physician-attributable diﬀerences in patient management in order to foster a better collaborative and educational environment to help critical care systems adapt to emerging ideas. The ﬁrst axis of the model measured interventionism (early, aggressive treatment) versus minimalism (’wait and see’) preferences. The second axis measured individualism versus collectivism.
On July 12, a preprint by Neil et al. described a Bayesian meta-analysis of ivermectin’s eﬀectiveness in COVID-19 .
On July 13, a news report in the Atlantic by Mazer discussed FDA’s recent approval of Alzheimer’s disease medicine aducanumab . It said aducanumab was approved despite scant evidence of beneﬁt, and against the nearly unanimous advice of the agency’s expert advisers, with ten members against approval and one being uncertain . Aducanumab was priced at USD 56,000 a patient per year. The estimated cost of treating all patients with it was larger than NASA’s yearly budget. The article said that ‘the actions of drug regulators, like those of industrial polluters, are often freighted with unacknowledged externalities .. . the FDA speciﬁcally does not really worry about those larger societal issues and doesn’t really worry about cost. . . instead, the agency is judged by how many drugs it can approve’.
On July 14, an opinion by Flam said that high hopes for ivermectin owe more to politics than to science.
On July 14, Mathachan et al. reviewed current uses of ivermectin in dermatology, tropical medicine andCOVID-19 .
On July 15, an article by Ravikirti et al. describing a clinical trial in India on patients with mild to moderate disease (n=112) using 12 mg of ivermectin on two consecutive days did not produce statistically signiﬁcant results .
On July 15, referring to a 2020 preprint by Elgazzar et al. , a news article by Davey in the Guardian said that a huge study supporting ivermectin as COVID-19 treatment had been withdrawn over ethical concerns . The article described ivermectin being promoted by right wing ﬁgures, then interviewed a person described as a medical student, Jack Lawrence, who had analyzed the preprint and the associated dataset for an assignment as a part of his master’s degree. He had found that the introduction section appeared plagiarized, raw data apparently contradicted the study protocol on several occasions, there were errors in data formatting, and the dataset didn’t match the numbers in the preprint. He also described that ivermectin hype was ‘dominated by a mix of right-wing ﬁgures, anti-vaxxers and outright conspiracists’.
A data analyst Nick Brown had helped Lawrence to analyze the data. He said that the main error was that at least 79 of the patient records were obvious clones of other records. An epidemiologist, Gideon Meyerowitz-Katz, commented that the data appeared totally faked, and since the study had been included in most meta-analyses, if removed, the conclusions of these meta-analyses would have their conclusions entirely reversed. Yet another researcher said the data appeared fabricated. Lawrence concluded that ‘something is clearly broken in a system that can allow a study as full of problems as the Elgazzar paper to run unchallenged for seven months . . . thousands of highly educated scientists, doctors, pharmacists, and at least four major medicines regulators missed a fraud so apparent that it might as well have come with a ﬂashing neon sign’.
On July 15, a post by Lawrence on an online disinformation website discussed retraction of the preprint by Elgazzar et al. . Jack Lawrence introduced himself on his blog as a journalist and a disinformation researcher .
On July 15, a blog post by Brown analyzed details of the study by Elgazzar et al .
On July 15, a blog post by Meyerowitz-Katz pictured ivermectin for COVID-19 research as ‘potentially the most consequential medical fraud ever committed’ .
On July 15, the Covid Analysis group removed Elgazzar et al. from their meta-analysis. Since the study was a preprint, the analysis of 37 peer-reviewed studies (n=11,352) in the July 15 version 99 of 60 studies  remained unchanged, indicating 88% eﬃcacy in prophylaxis (95 % CI 70%-95%), 74% eﬃcacy in early treatment (95% CI 58%-84%) and 42% eﬃcacy in late treatment (95% CI 19%-58%). Since Elgazzar etal. only concerned prophylaxis and late treatment, also the early treatment results remained unchanged, indicating 64% reduction in mortality (95% CI 15%-85%). In comparison to the previous, July 9 version 98 of 62 studies  (Elgazzar study included prophylaxis (n=200) and late treatment (n=400) parts), the new version indicated the same or slightly improved prophylaxis eﬃcacy but slightly widened conﬁdence intervals, with all studies indicating 85% (95% CI 75%-91%) vs 85% (95% CI 75%-92%) eﬃcacy, and RCTs indicating83% (95% CI 39%-95%) vs 84% (95% CI 25%-96%) eﬃcacy. For late treatment, the new version indicated lower eﬃcacy, with all studies indicating 46% (95% CI 30%-59%) vs 43% (95% CI 26%-56%) eﬃcacy, and RCTs indicating 40% (95% CI 11%-60%) vs 29% (95% CI 3%-48%) eﬃcacy.
On July 16, FLCCC and BIRD gave a joint statement saying that there was no scientiﬁc basis to state that the removal of one study from meta-analyses would ‘reverse results’, yet the Guardian article had reported it as a fact . They also said that according to the most recent analyses by BIRD, excluding the Elgazzar data from the meta-analyses by Bryant and Hill did not change the conclusions of these reviews, with the ﬁndings still clearly favoring ivermectin for both prevention and treatment. They added that even the prestigious Institute Pasteur in France had conﬁrmed that the evidence was sound .
On July 16, Hill tweeted that ‘after removal of Elgazzar trial from ivermectin meta-analysis, borderline signiﬁcant eﬀects still seen for hospitalization and survival, but small number of endpoints. More evidence still needed from large ongoing randomized trials – must be continued’ .
On July 16, a news article said that a study that had ‘lit up the right-wing sphere of COVID deniers had been retracted over questionable methods’, adding that it was ‘just totally faked’ .
On July 16, a South African news article reviewed the retraction . It also featured video interviews of patients, doctors and oﬃcials which concentrated on the black market of ivermectin in South Africa and the possible dangers of counterfeit medications.
On July 16, an opinion by Razak, the rector of International Islamic University of Malaysia, aimed at ‘setting the pace for a more courageous narrative’ about ivermectin’s possibilities in COVID-19 .
On July 17, the United Arab Emirates announced the treatment results for intravenously administered monoclonal antibody sotrovimab, produced by GlaxoSmithKline, in treating mild to moderate COVID-19cases among high-risk outpatients . 6,175 patients were administered sotrovimab in Abu Dhabi between30 June and 13 July. Within 14 days, 97 percent of recipients achieved full recovery. There were zero deaths. 1 percent were admitted to ICU.
On July 17, a news report by Weisser described that early in the pandemic in Indonesia, an enterprising philanthropist Haryoseno made ivermectin available to the masses for free or at low cost, which resulted in Indonesia having an extremely low COVID-19 mortality rate. On June 12, 2021, however, in line withthe WHO recommendation, the ministry of health decided to disallow ivermectin and threatened Haryoseno with a ﬁne and a ten-year jail sentence. Subsequently, the supply of ivermectin dried up and mortality increased ﬁve-fold . About Australia, the report noted that clinician Mark Hobart had been reported to the Australian Health Practitioner Regulation Agency (AHPRA) which had decided that there had been no infringement. Subsequently, federal health minister had written that oﬀ-label ivermectin prescribing was not regulated or controlled by the Therapeutic Goods Administration (TGA) but was at the discretion ofthe prescribing physician. The physicians had formed Covid Medical Network , the members of which predominantly followed a ‘triple-therapy protocol’ developed by Thomas Borody, consisting of ivermectin, zinc and doxycycline . The report also said that although the research on ivermectin for COVID-19 had originated from Australia, the researchers had been starved of resources and the discovery ignored.
On July 20, BBC wrote about Indonesia, saying that local media reports had incorrectly stated that theIndonesian authorities had granted ivermectin emergency approval . The reports had been based on a July 15 statement issued by the Food and Drugs Authority of Indonesia (BPOM) in which ivermectin had been listed together with other drugs, two of which had had emergency approval. Shortly afterwards the head of BPOM had told local media that no emergency approval had been given to ivermectin. It had been listed because it was undergoing clinical trials at eight hospitals, the results of which were not expected until October.
On July 20, Med Page Today wrote about retraction of the preprint by Elgazzar et al. .
On July 20, a Swedish medical newspaper published an opinion by three Swedish doctors suggesting that Sweden should follow the example of the Czech Republic, Slovakia and other countries which had adopted ivermectin .
On July 22, Los Angeles Times wrote that ‘ivermectin, another bogus treatment, becomes a darling ofconspiracy-mongers’ . In addition to reviewing the main points behind the retraction of the Elgazzaret al. preprint the columnist delved into an analysis of ivermectin politics, saying it was rather diﬀerent from hydroxychloroquine controversy, as ‘the political underpinning of the ivermectin craze involves a conspiracy-infused attack on the pharmaceutical and medical establishment. In this it resembles the antivaccine movement .. . like anti-vaxxers, ivermectin advocates claim that information about the drug is being “suppressed,” generally by agents of Big Pharma; the core idea is that because drug companies can’t make very much money out of a drug available in generic form, they prefer to foist vaccines, on which they canmake billions of dollars in proﬁts, on the innocent public . . . let’s be clear: information about the drug isn’t being “suppressed” for political reasons. It’s being treated as what it is: dangerous misinformation’.
On July 23, an interview of science writer Matt Ridley in the Wall Street Journal said that science had lost the public’s trust and that the politicization of science had led to a loss of conﬁdence in science as an institution, and whereas the distrust may have been justiﬁed it left a vacuum that was often ﬁlled by lessrigorous approaches to knowledge . Ridley pointed to a distinction between ‘science as a philosophy’ and‘science as an institution’, with the former wanting to remain open-minded, and the latter wanting to present a uniﬁed and authoritative voice, fostering a naive belief in the supremacy of scientists in understanding the world, luring politicians to aﬃliate themselves with this alleged power. Regardless, scientists often deliberately published things that ﬁt with their political prejudices, ignored things that didn’t, or presented models based on rather extreme assumptions. Pessimistic predictions often being more popular in the media introduced a bias. A third conceptualization of or a type of identiﬁcation with the concept of science,‘science as a profession’, had become oﬀ-puttingly arrogant and political, permeated by motivated reasoning and conﬁrmation bias, with increasing numbers of scientists falling prey to groupthink . According to Ridley, the tendency of scientiﬁc establishment ‘to turn into a church, enforcing obedience to the latest dogma and expelling heretics and blasphemers’ had previously been kept in check by the fragmented natureof the scientiﬁc enterprise but social media was eliminating the space for heterodoxy, leaving those believingin science as a philosophy increasingly estranged from science as an institution.
On July 23, an article by Mansour et al. described a preclinical tolerance study on the safety of inhaled lyophilized ivermectin formulation indicating 127-fold increase in drug aqueous solubility but also safety issues .
On July 24, World Ivermectin Day was organized by the BIRD group, the FLCCC, TrialSite News and 15 other aﬃliates . Panel discussions included Shabnam Palesa Mohamed in conversation with PinkyN.J. Ngcakani (South Africa) and Wahome Ngare (Kenya); Erin Stair in conversation with Hector Carvallo(Argentina), Lucy Kerr (Brazil) and Flavio Cadegiani (Brazil); Shabnam Palesa Mohamed in conversation with Pierre Kory (US), Ira Bernstein (Canada) and Sabine Hazan (United States); Vincent Rey Vicente(US) in conversation with Iggy Agbayani, Homer Lim and Allan Landrito (Philippines), and PriyamadhabaBahera, Binod Kumar Patro, Biswa Mohan Padhy and Rashmi Ranjan Mohanty (India); Daniel O’Connorin conversation with Juan Bertoglio (Chile) and Matjaˇz Zwitter (Slovenia); Daniel O’Connor in conversationwith Juan Chamie (US), Pierre Kory (US) and Nathi Mdladla (South Africa).
On July 25, a preprint by Ontai et al. described a nationwide implementation of multi-drug COVID-19inpatient and outpatient treatment protocol CATRACHO in Honduras since May 3, 2020 [106,107]. The inpatient protocol consisted of dexamethasone, colchicine, tocilizumab, ivermectin, zinc, azithromycin andheparin. There were two outpatient protocols, one consisting of mouthwash, azithromycin, ivermectin andzinc, and the other consisting of prednisone, colchicine and rivaroxaban. The results indicated a case fatalityrate (CFR) decrease from May 3,2020 baseline of 9.3% to 3.0%, or from June 10, 2020 baseline of 5.0% to3.0%. Mexico used as a control country failed to show a similar decline.
On July 27, upon receiving a Special Benevolence Award from Tan Sri Lee Kim Yew of Malaysia on World Ivermectin Day, Kory of the FLCCC gave a lecture outlining the history of ivermectin in COVID-19 [108,109].
He mentioned that the MATH+ protocol had been adopted as the standard protocol in Ukraine, and thatthe hospital mortality rate there was the lowest of the countries in the area.
On July 27, press releases by Cochrane Deutschland and the University of W¨urzburg stated that there was no evidence of ivermectin’s eﬃcacy [110,111].
On July 27, the university hospital of St. Anny in Brno in the Czech Republic published a report about their ivermectin treatment, saying it had been well tolerated and likely had a positive eﬀect on COVID19 . Ivermectin had been available at hospitals and for outpatient treatment since late 2020. Head of internal cardioangiology clinic Michal Rezek described the results of their analysis of 150 patients with a mean age of 63 years (32-93 years, median 65 years) treated between December 2020 and January 2021 with two doses of 0.2 mg/kg of ivermectin. 117 patients had required oxygenation and corticosteroids, 42 had required high-ﬂow oxygen, and 17 had received also remdesivir. 18 patients had needed mechanical ventilation, six of which had died. Hospital mortality had been 10%, with the average age of the deceased being 75 years. There had been no control group. The hospital intended to continue ivermectin treatment and was preparing a RCT in collaboration with Masaryk University and Czech Clinical Research InfrastructureNetwork (CZECRIN) . Lack of COVID-19 patients was mentioned as a possible obstacle to the trial. Rezek said a combination antiviral therapy with ivermectin and remdesivir was likely more eﬀective than single-agent therapies.
On July 28, a Cochrane review by Popp et al. concluded that its authors were uncertain about the eﬃcacy and safety of ivermectin for treatment or prophylaxis of COVID-19 . With regard to late treatment(inpatients), the authors were uncertain whether ivermectin compared to placebo or standard of care reduced or increased mortality (RR 0.60, 95% CI 0.14-2.51, 2 studies, n=185, very low certainty), mechanical ventilation (RR 0.55, 95% CI 0.11-2.59, 2 studies, 185 participants, very low certainty), need for supplemental oxygen (0 participants required supplemental oxygen, one study, 45 participants, very low certainty), adverse events within 28 days (RR 1.21, 95% CI 0.50-2.97, one study, 152 participants, very low certainty), or viral clearance at day seven (RR 1.82, 95% CI 0.51-6.48, 2 studies, 159 participants, very low certainty). With regard to outpatients, the authors were uncertain about mortality up to 28 days (RR 0.33, 95% CI 0.018.05, 2 studies, 422 participants, very low certainty), mechanical ventilation (RR 2.97, 95% CI 0.12-72.47,one study, 398 participants, very low certainty) and symptoms resolution up to 14 days (RR 1.04, 95% CI0.89-1.21, one study, 398 participants, low certainty). With regard to prophylaxis there was only one eligible study, with mortality up to 28 days being the only outcome eligible for primary analysis; the authors were uncertain whether ivermectin reduced or increased mortality compared to no treatment (zero participants died, one study, 304 participants, very low certainty). The Covid Analysis group criticized the meta-analysis for being ’a very biased meta analysis designed to exclude almost all studies’ .
On July 28, an opinion in the Wall Street Journal questioned FDA’s negative stance on ivermectin . The next day the authors wrote that they had not been aware of the retraction of the Elgazzar et al. study, yet stated that ‘the broader point stands: there’s strong evidence of ivermectin’s eﬃcacy in COVID-19’ .
On July 28, GlaxoSmithKline (GSK) and Vir Biotechnology announced a joint procurement agreement with European Commission to supply up to 220,000 doses of sotrovimab , a contract worth USD 462 million at the wholesale price of USD 2,100 per dose. The agreement enabled participating European Union member states to quickly purchase sotrovimab, following local emergency authorization or authorization at the EUlevel, to treat high-risk patients with COVID-19 who might beneﬁt from early treatment with sotrovimab.
On July 29, an article in Times of India explained a much higher rate of infections in the state of Kerala bylower COVID-19 seropositivity .
On July 30, a Czech Republic newspaper published a timeline of ivermectin-related events in the CzechRepublic .
On July 30, an article by Rella et al. suggested that in the current conditions the vaccines-only pandemic response may create vaccine-resistant strains [121,122].
On July 31, Kiekens interviewed George Fareed about outpatient treatment protocols for newly infected andfor long haul COVID-19 syndrome (LHCS) patients, implemented jointly with Brian Tyson on thousands of patients in the US . For neurological LHCS symptoms in some instances, Fareed suggested a two to three-day high-dose ivermectin treatment as suggested by Alessandro Santin .
On August 2, a news article from Israel reported on a clinical trial by Biber et al. (NCT04429711) , saying that ivermectin could help reduce the length of infection for less than a USD 1 per day, and that only 13%of ivermectin-treated patients were infectious after six days, compared with 50% of patients in the placebo group . Schwartz, the leader of the trial, said that three journals had rejected the paper: ‘No one even wanted to hear about it. You have to ask how come when the world is suﬀering’.
On August 2, an open letter by Covid Medical Network stressed the importance of early treatment and noted that the federal health minister had acknowledged and even encouraged oﬀ-label prescribing of some treatments including ivermectin .
On August 2, an article by Reardon in Nature said that shocking revelations of widespread ﬂaws in the data of a preprint study by Elgazzar et al. dampened ivermectin’s promise and highlighted the challenges of investigating drug eﬃcacy during a pandemic . Gideon Meyerowitz-Katz, an Australian epidemiologist,said he had lost all faith in the results of ivermectin trials published to date.
On August 2, an article by Sengthong et al. said that repeated ivermectin treatment induced ivermectin resistance in Strongyloides ratti infected rats .
On August 3, an article by Santin et al. reviewed the current status of ivermectin research, mentioning that the indicated biological mechanism of ivermectin, competitive binding with SARS-CoV-2 spike protein, was ikely non-epitope speciﬁc, possibly yielding full eﬃcacy against emerging viral mutant strains .
On August 3, BBC wrote about the mystery of rising infections in India’s Kerala . The southern Indian state of Kerala, with barely 3% of India’s population, accounted for more than half of the country’s new COVID-19 infections. Kerala was testing more than double the people per million compared to the rest of the country. Antibody tests survey revealed that only 43% people above the age of six in Kerala had been exposed to the infection, compared to 68% nationwide. Kerala had fully vaccinated more than 20% of its eligible population and 52% had received a single jab (70% of people over 45 years) which was much higher than the national average. BBC wrote that the state appeared to be testing widely, reporting cases honestly and vaccinating quickly, ensuring that future waves of infection would be less severe. Yet Kerala was said to be at an early stage in runaway exponential growth of cases. More forceful enforcement of rolling lockdowns was suggested as a solution.
On August 3, George Fareed discussed early treatments on Fox News television .
On August 5, an article by Behera et al. described a prospective cohort study (n=3,532) in India, indicatingthat two doses of oral ivermectin (0.3 mg/kg/dose given 72 hours apart) as chemoprophylaxis among healthcare workers reduced the risk of COVID-19 infection by 83% in the following month (6% vs 15%, adjustedrelative risk 0.17; 95% CI, 0.12-0.23) .
On August 5, a preprint by Rana et al. described an in silico study showing strong binding aﬃnity ofivermectin and doxycycline for SARS-CoV-2 main protease 3CLpro, and increased binding aﬃnity for thecombination of both [134,135].
On August 5, a Finnish technology magazine wrote about ivermectin, saying that according to FLCCC,there was already an eﬀective medication for COVID-19 but it was rarely used . A head of unit at theFinnish Medicines Agency (FIMEA) commented that doctors were allowed to prescribe it oﬀ-label, providedthat the patient was informed about it not being oﬃcially approved for COVID-19. The oﬃcial commentedthat ‘in an international comparison the Finnish medical community is quite conservative about adoptingnew treatments without a suﬃciently strong evidence base’. Also, a process to oﬃcially adopt ivermectin forCOVID-19 could only be initiated by a producer of ivermectin or the European Medicine Agency (EMA).
On August 6, an article by Kow et al. reviewed sample size calculations in ivermectin trials, indicating thatexisting trials had been very underpowered .
On August 6, US National Institutes of Health (NIH) Collaboratory published a video interview of EdwardJ. Mills, the head researcher of Together adaptive platform trial . Mills discussed interim results of their outpatient trial which included ﬂuvoxamine and ivermectin (0.4 mg/kg for three days). For ivermectin,the risk reduction for extended emergency room observation or hospitalization was 9% (86/677 vs 95/678,RR 0.91, 95% CI 0.69-1.19) and for mortality 18% (RR 0.82, 95% CI 0.44-1.52); these were not statistically signiﬁcant. Mills commented that ivermectin had had ’no eﬀect whatsoever’ on their primary and secondary endpoints. For ﬂuvoxamine, the risk reduction for extended emergency room observation or hospitalization was 31% (74/742 vs 107/738, RR 0.69, 95% CI 0.52-0.91) and for mortality 29% (17/742 vs 24/738, RR0.71, 95% CI 0.39-1.29); the ﬁrst endpoint was statistically signiﬁcant while the second was not. The trial was done at ten locations in Minas Gerais, Brazil. It was unclear whether over-the-counter ivermectin usehad been an exclusion criteria. At the time the gamma variant was prevalent and assumed to cause higher viral loads and a more severe disease than most other variants. The Covid Analysis group criticized various aspects of the trial .
On August 6, a report on SARS-CoV-2 variants by Public Health England indicated that concerning deathswithin 28 days of positive specimen date between February 1 and August 2 there had been 71 deaths in people under 50 years and 670 in people over 50 years . In the ﬁrst group, 18% had been vaccinatedtwice and 68% were unvaccinated. In the second group, 58% had been vaccinated twice and 31% were unvaccinated.
On August 6, a podcast by Nature discussed ivermectin .
On August 9, a commentary by US medical doctor using a pseudonym Justus R. Hope described a ‘blackouton any conversation about how ivermectin beat COVID-19 in India’ [142,143]. It claimed that the US newsmedia were trying to confuse the public with false information by saying the deaths in India were ten times greater than oﬃcial reports. Using August 5 numbers as examples the author said that in ivermectin-using states of India such as Uttar Pradesh with a population 240 million of which 4.9% were fully vaccinated there were 26 daily cases and three deaths, in Delhi with a population of 31 million of which 15% were fully vaccinated there were 61 daily cases and two deaths, in Uttarakhand with a population of 11.4 million of which 15% were fully vaccinated there were 24 daily cases with zero deaths. In states not using ivermectin such as Tamil Nadu with a population of 78.8 million of which 6.9% were fully vaccinated there were 1,997daily cases with 33 deaths. In the US with a population of 331 million of which 50.5% were fully vaccinated there were 127,108 daily cases with 574 deaths. He compared FDA’s and WHO’s ban on ivermectin to Pope’sban on all books and letters that argued the Sun was the center of the universe instead of Earth, adding that the US government was ‘all-in with vaccines with the enthusiasm of a 17th century Catholic church’.
On August 10, a news story by Yahoo! Japan reported that a Japanese clinician Kazuhiro Nagao, appearingon the Fuji TV television program, had suggested that ivermectin should be distributed to all Japanese nationals in advance to be taken after COVID-19 infection, and that COVID-19 should be in the same administrative category as seasonal inﬂuenza in order to avoid delays and make early treatment possible .
On August 10, a news report from La Pampa province of Argentina described minister of health MarioRub´en Kohan releasing the latest results of the implementation of a monitored intervention program on the use of 0.6 mg/kg of ivermectin for ﬁve days in 3,269 treated patients versus 18,149 untreated patients[145,146]. The risk of death was 27.4% lower (RR 0.73) and the risk of death or ICU admission was 38.0%lower (RR 0.62). For people over 40 years of age the risk of death was 33.4% lower (RR 0.67). For people over 40 years of age and with comorbidities the risk of death was 44.0% lower (RR 0.56).
On August 11, Los Angeles Times wrote about ivermectin having ‘no eﬀect whatsoever’ in the Togethertrial . The head researcher Mills said that ‘in our speciﬁc trial we do not see the treatment beneﬁt that a lot of the advocates believe should have been seen’. He complained that many researchers had faced unprecedented abuse from advocates of speciﬁc treatments.
On August 11, an article by Cobos-Campos et al. reviewed ivermectin for COVID-19 .
On August 12, vaccine expert Geert Vanden Bossche, who on May 24, 2021 had proposed mass chemoprophylaxis with ivermectin , demanded stopping of COVID-19 mass vaccination . A rationale for the demand was the increased infectiousness of new variants already noted with respect to the alpha and delta variants, both more infective than the original variant, and the delta variant being signiﬁcantly more infective than the alpha variant. Bossche expected this trajectory to continue, possibly resulting in an uncontrollable situation. In Bossche’s view, the increased infectivity had resulted from a natural selection of increasingly vaccine immunity escaping variants in the vaccinated part of the population. In other words, mass vacci11nation had created an evolutionary pressure for development of these variants which were then transferred to the non-vaccinated population. In addition, vaccine-induced antibodies possibly competed with natural antibody based, variant-nonspeciﬁc immunity, possibly rendering the population more vulnerable to some vaccine immunity escaping variants. The issue was also taken up by other researchers .
On August 12, a preprint by Elavarasi et al. described a retrospective study about hospitalized patients in India which did not show a statistically signiﬁcant result .
On August 12, an article by Pedroso et al. described that self-prescribed use of early ivermectin treatment by 45 healthcare workers in Brazil was associated with a lower rate of seroconversion in a dose-dependentresponse .
On August 13, an article by Zhou et al. suggested that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers .
On August 13, on NIH Collaboratory, Smith discussed the history of proposed therapies for COVID-19 andthe adaptive platform trial ACTIV-2 .
On August 14, a Japanese clinician Kazuhiro Nagao wrote in a blog post that he had been harassed and had received death threats after appearing on TV and telling about treating 500 COVID-19 patients with ivermectin with no deaths [156,157].
On August 14, Kiekens interviewed an Italian physician Andrea Stramezzi about his early treatment protocol and his telehealth treatment method . He was using hydroxychloroquine as a part of the outpatient protocol due to its easy availability. According to Stramezzi, it was useful in the ﬁrst few days. Initially in the pandemic it had been provisionally recommended , then banned . Stramezzi had initiated a legal proceeding about the ban, initially winning the case but subsequently losing an appeal. Regardless,the judge had decreed that physicians were free to prescribe medications oﬀ-label at their discretion. In addition, the protocol had included anti-inﬂammatories such as aspirin, and bromhexine. Also vitamins C and D were used, although Stramezzi did not consider high levels of vitamin D suﬃcient to prevent COVID19. Additionally, vitamin K was administered separately from vitamin D due to their antagonism. A later addition, ivermectin, useful also in later stages to reduce replication of the virus, needed to be imported from the neighboring countries. Stramezzi said that about 10% of Italians had a genetic vulnerability toSARS-CoV-2 induced hyperinﬂammation. For this group, prevention with corticosteroids and enoxaparin was necessary. He said that there were approximately 1,500 physicians in Italy working with the similar protocols, exchanging information with each other. The public’s awareness of early treatments in Italy was still low because health authorities did not recommend it or talk about it, instead just recommendingparacetamol and waiting for severe pneumonia to emerge before contacting healthcare facilities. Stramezzisaid they had met Sileri, a physician/researcher and deputy minister of health (M5s) [161,162], for an hour.
Sileri had said he was aware of the therapeutical options, had treated a hundred patients himself, and hadco-authored an article about the genetic defect . Also, the parliament of Italy had voted in favor ofearly treatments . Regardless, after several months nothing had happened with regard to adoption of these treatments. Stramezzi was developing a free mobile phone app for doctors who had too many patients or who were unsure of how to treat COVID-19: the app would give suggestions for a suitable treatment protocol.
On August 16, a letter to the editor by Chahla et al. in the American Journal of Therapeutics described a randomized controlled trial (n=234) in Argentina with ivermectin and iota-carrageenan as pre-exposureprophylaxis for health care workers (NCT04701710) [165,166,167]. The treated group (n=117) received 6mg ivermectin every seven days, and six nasal sprays of iota-carrageenan per day for 4 weeks. The risk ofCOVID-19 infection was 84.0% lower (3.4% vs 21.4%, RR 0.16, p=0.001), and the risk of moderate or severe disease was 95.2% lower (0.0% vs 8.5%, RR 0.05, p=0.002). The authors hypothesized that the combination treatment formed a double viral barrier: ﬁrst, carrageenan behaved as a mucolytic agent in a barrier of sulfated polysaccharides with negative charge in the nasal cavity; second, ivermectin decreased viral load by systemic cellular action.
On August 16, an article by Winter examined the ongoing discussion about ivermectin .
On August 17, an article by Gonz´alez-Paz et al. described an in-silico elastic network model analysis of ivermectin components (avermectin-B1a and avermectin-B1b) providing a biophysical and computational perspective of proposed multi-target activity of ivermectin for COVID-19 [169,170].
On August 17, Associated Press reported that ’dozens of people in Oregon have contacted the state’s poisoncenter after self-medicating against COVID-19 with a drug used to treat parasites, with ﬁve becoming hospitalized and two of them winding up in intensive care units’ .
On August 18, Los Angeles Times wrote that ﬂuvoxamine may actually work against COVID-19 .
On August 19, an article by Gonz´alez-Paz et al. described an in silico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting diﬀerent and complementary inhibitory activity of each component, with an aﬃnity of avermectin-B1b for viral structures, and of avermectin-B1a for host structures [173,174].
On August 20, an article by Amaya-Aponte reviewed ivermectin in COVID-19 .
On August 20, the investigational monoclonal antibody sotrovimab was granted a provisional approval forthe treatment of COVID-19 in Australia .
On August 20, a letter by Popp et al. in the BMJ said that the diﬀerent assessments between Popp et al’sCochrane meta-analysis and the one by Bryant et al. were partly due to baseline data of included studies:Bryant et al. pooled heterogeneous patient populations, interventions, comparators and outcomes whereasPopp et al. did not; thus, according to Popp et al., Bryant et al. compared apples and oranges, ‘serving a large bowl of a colorful fruit salad’ . The authors accused Bryant et al. of ‘creating pseudotrustworthiness for substances that cannot be considered eﬀective and safe treatment options nor game changers, at this stage’.
On August 21, an article by Karvanen et al. described a new algorithm for causal eﬀect identiﬁcation: do search based on do-calculus . The algorithm might allow for improving clinical trial result analysis [179,180,181].
On August 21, due to overlap and confusion with the I-MATH+ prophylaxis and early outpatient treatment protocol, the FLCCC discontinued its I-MASS mass prophylaxis and home treatment protocol introduced a few months earlier .
On August 21, the US Food and Drug Administration (FDA) tweeted about ivermectin, stating that ‘You are not a horse. You are not a cow. Seriously, y’all. Stop it.’ . The tweet linked to FDA’s March 2021advisory against ivermectin .
On August 21, a Slovenian newspaper reviewed ivermectin, mentioning two previous articles published in the same newspaper written by a Slovenian ivermectin proponent Matjaˇz Zwitter [185,186].
On August 21, a blog post by Meyerowitz-Katz discussed a study by Cadegiani et al. , claiming that thedata in a spreadsheet uploaded by the authors didn’t look real: ’data for this study may not be fake, but it is at least incredibly suspicious’ [187,188].
On August 21, a preprint by Izcovich et al. presented a systematic review about bias as a source of inconsistency in ivermectin trials . Based on a review of 29 RCTs with 5,592 cases the authors concluded that previous reports about ivermectin’s beneﬁts were based on potentially biased results, and further research was needed.
On August 22, an Indian geriatrician, preventive cardiologist and anti-aging specialist Lenny Da Costa described ivermectin use in India [190,191]. According to Costa, beginning from March 2020, India distributed an outpatient home treatment kit containing hydroxychloroquine, azithromycin, doxycycline, ivermectin and vitamin C. In March 2021, ignoring evidence from India, WHO stated that ivermectin should not be used.
The statement was given by an Indian epidemiologist, WHO chief scientist Soumya Swaminathan. A group of Indian physicians ﬁled a legal case against her. To protect Swaminathan, Indian central government removedivermectin from oﬃcial recommendations. However, state governments were responsible for guidelines for medical care in the states, not the central government; most states continued the use of ivermectin. Costasaid that no-one had stopped using ivermectin but they did not advertise the fact. According to Costa,during the deadly second wave in April-May 2021, India’s most populous state, Uttar Pradesh, reduced the number of daily cases from 60,000 to 15,000 in a month by distributing ivermectin for everyone for free. Clinicians did not wait for RT-PCR test results; instead, medication was started immediately on the presentation of symptoms. Prescriptions were given for free by telemedicine (WhatsApp). Ivermectin prevented people from infecting others, especially family members. Also, numerous physicians had been using ivermectin since March 2020 for prophylaxis, with none of them getting infected. On June 29, 2021, the government of Uttar Pradesh announced a home treatment kit for children, containing paracetamol, multivitamins and ivermectin. Costa claimed that India’s success in controlling the second wave was primarily due to an early administration of ivermectin, doxycycline, zinc and other medications used for early treatment.
On August 23, a medical doctor writing under a pseudonym Justus R. Hope continued on India’s ‘ivermectin blackout’ [192,193]. On August 15, Kerala, a state reportedly not using ivermectin, with a population of approximately 3% of India’s population, had accounted for 56% of India’s new cases and 25% of India’s new deaths. Delhi, a state with nearly the same population size as Kerala but using ivermectin, accounted for 0.2% of new cases and 0% of deaths. Uttar Pradesh, with a population almost eight times larger than
Kerala, accounted for 0.09% of new cases and 0.2% of deaths. Hope wrote that Kerala ranked in the top ﬁve most vaccinated of India’s 29 states, adding that Kerala’s failure in comparison to most other states of India could be explained by the facts that Kerala had not used ivermectin for early treatment whereas most other states had, and that ivermectin lowered the viral load and inhibited transmission whereas vaccination did not, giving a false sense of security. Those with prior infection, negative test result, or at least one vaccine dose (56% of adults) had been exempted from lockdown . Hope called Kerala’s comparatively highvaccination rate its most problematic feature leading to rampant viral transmission. Kerala had adopted ivermectin in April but restricted its use to severe cases with additional risk factors. On August 5, Kerala had removed ivermectin from state guidelines completely. In contrast, Uttar Pradesh had been the ﬁrst stateto introduce large-scale prophylactic and therapeutic use of ivermectin. The state had treated all contacts of an infected patient prophylactically with ivermectin. The lesson, Hope said, was that ivermectin could make up for the low use of vaccination but vaccination could not make up for the low use of ivermectin.
On August 23, ABC News report written by a medical toxicology fellow and an emergency medicine physician in New York stated that health oﬃcials had said that a potentially dangerous, unproven deworming drugs hould not be used to treat COVID-19 . The report blamed social media for informing people about the medication ‘not authorized by independent regulators at the FDA’ (see e.g. ). Not a single trial to prove ivermectin’s usefulness existed and an interviewee advised that people ‘don’t have to go with something that doesn’t have a scientiﬁc basis’.
On August 23, CBS News reported that oﬃcials had warned against using anti-parasite drug for COVID19 .
On August 24, Mother Jones magazine interviewed Boulware, an ivermectin researcher, involved in a University of Minnesota trial (NCT04510194) [198,199]. Boulware had received hostile messages calling him ’are embodied Josef Mengele’ from people believing that ivermectin was a miracle cure and placebo-controlled trials were therefore unethical. Another researcher at Washington University in St. Louis commented on the polarization, saying that if she tweeted something about vaccines as positive, she was being attacked by people pro early treatment, and if she tweeted about potential treatments, she provoked the ire of vaccine advocates who ‘kind of seem to suppress any information about early treatment, maybe because they feel like it’s going to make people think they don’t need to be vaccinated’. The article also described Steve Kirsch’s frustration with the government’s unwillingness to recommend treatments on the basis of small trials with encouraging results. Researchers also worried that the recent reports of ivermectin self-dosing could scare people oﬀ of enrolling in any kind of treatment trials in the future.
On August 25, an article by Mohan et al. described a trial (RIVET-COV, n=157) investigating the eﬀect of single-dose oral ivermectin (12 or 24 mg) in mild and moderate COVID-19 which indicated no statistically signiﬁcant eﬀects on viral load or RT-PCR negativity .
On August 25, on the social media platform Reddit, subreddit r/ivermectin which had been a public, uncensored discussion forum initiated a year before for discussions related to ivermectin research and treatments,was ﬂooded with tens of horse-themed pornographic cartoon images, in reference to ivermectin as ‘horse paste’, as well as hundreds of sexual, oﬀensive or irrelevant comments. The moderator said the attack had been coordinated by a group of moderators of other, large subreddits, yet refused to remove the irrelevant content, referring to his disbelief in censorship .
On August 25, in a FLCCC weekly update, endocrinologist and researcher Fl´avio Cadegiani described his experience in the state of Amazonas in Brazil during a gamma variant outbreak in 2021 (the gamma variantwas considered to cause a more severe disease than the delta variant) . The research group had visitedvarious cities with hospitals overwhelmed with COVID-19 patients. However, in the city of Coari located afew hundred kilometers west from Manaus there had been no hospitalized COVID-19 patients at all. At ﬁrst Cadegiani had been unable to get an explanation to the situation but later, in private, a health oﬃcial had revealed that the city had been providing ivermectin for its whole population for two months already. As to the question why the explanation had not been given immediately the oﬃcial replied that she had been afraid of being accused of giving unapproved treatments. Cadegiani said the experience had been shocking.
He added that secondary endpoints in single-agent trials were important indicators of possible eﬃcacy as a component in a multi-agent treatment protocol.
On August 25, in the FLCCC weekly update, Kory and Marik discussed the addition of dual anti-androgentherapy (dutasteride 2 mg on day one followed by 1 mg daily for ten days , and spironolactone 100 mg twice daily for ten days ) to their delta variant early treatment protocol which at the time included twelve components . They stated the addition provided ‘massive improvements’.
On August 26, Krolewiecki et al. published additional details about their trial on the antiviral eﬀect of high-dose ivermectin in COVID-19 .
On August 26, Centers for Disease Control and Prevention (CDC) reported that ivermectin prescriptionsfrom US pharmacies had increased 24-fold from the pre-pandemic baseline . Ivermectin-related calls to poison control centers had increased ﬁve-fold, respectively. The report gave two examples of adverse eﬀects:one patient becoming disoriented after taking tablets of unknown strength (5 tablets per day for ﬁve days),and another patient presenting with confusion, drowsiness, visual hallucinations, tachypnea and tremors after drinking an injectable form of veterinary ivermectin.
On August 26, Newsweek interviewed Joe Varon of the FLCCC saying that since a year ago he had treated thousands of COVID-19 patients in the US with oﬀ-label ivermectin in combination with other pharmaceuticals in the FLCCC treatment protocols . During the pandemic Varon had been widely featured in the US media but the reporters had chosen to not mention ivermectin.
On August 26, a news story in Vice magazine complained that Facebook did not properly censor ivermectin content and Facebook’s ivermectin groups were ‘unhinged and out of control’ [208,209].
On August 28, Newsweek reported about a far-right political commentator’s use of ivermectin for his COVID19 infection .
On August 28, Newsweek reported that a Republican representative from Texas had appeared to speak in support of unproven treatments for COVID-19, including ivermectin, a drug often used as a dewormer for cows and horses . The representative was also said to have praised president Trump and have raised concerns about vaccines.
On August 29, Anthony Fauci warned against using ivermectin for COVID-19 .
On August 29, Cohen wrote in Forbes that ivermectin had become embedded in a ‘cultural war’, commenting that ‘of all drugs right-wingers would have gravitated to, ivermectin and hydroxychloroquine are most unusual candidates, in that they’re largely used in humans in developing nations for conditions rarely seen in the US’ . Ivermectin for COVID-19 was pictured as unproven misinformation harming public health, and the politicization of the issue had been to the detriment of eﬀorts to contain the pandemic, taking attention away from clinically conﬁrmed instruments such as vaccines. The author worried that there were a surprising number of people in the medical profession who believed in ivermectin, such as the physician advisor to Florida’s governor. Cohen said that ‘these contrarians are not waiting for the completion of conﬁrmatory studies to disseminate their advice to the gullible minions to take ivermectin oﬀ-label, even if doing so may endanger lives’.
On August 30, Newsweek reported that an US hospital had refused to administer FLCCC member FredWagshul’s prescription for a patient, after which a judge had ordered the hospital to administer it . The next day, a regional US newspaper interviewed Wagshul who attributed the lack of adoption of ivermectinto ‘propaganda, money and big pharma’ .
On August 30, a report by German news agency said that ivermectin trials have been of a low quality and that Cochrane Deutschland and the University of W¨urzburg considered ivermectin ineﬃcacious .
On August 30, a video interview of Fernando Valerio describes Honduras’ treatment protocols in detail .
On August 31, a preprint by Omrani et al. presented a systematic review and meta-analysis of eﬀectiveness of ivermectin/doxycycline combination, concluding that based on low-quality evidence, the combination was accompanied with a shorter time of clinical recovery but did not signiﬁcantly reduce all-cause mortality, viral clearance, and hospital stay .
On August 31, Pfeiﬀer described patients’ experiences in US hospitals .
On August 31, Kory of the FLCCC accused the US National Institutes of Health (NIH) of being the main agent in the ‘war against ivermectin’ due to not having given a recommendation for ivermectin . Healso stated the FDA was only ‘running interference for [NIH] by telling jokes and lies’.
On August 31, a Swedish newspaper G¨oteborgs-Posten wrote about veterinary ivermectin use in the US .
On August 31, a preprint describing a randomized controlled trial of community-level surgical mask promotion in rural Bangladesh with 111,525 individuals in the intervention arm and 155,268 individuals in the control arm indicated 14% relative reduction in COVID-19-like symptoms, with absolute reductions of 7.5%vs 8.6%. Divided by age groups, diﬀerences were not statistically signiﬁcant in people under 50. In people between 50-60 years there was a reduction of 23%, and in people over 60 a reduction of 35%, respectively.
The impact of the intervention faded after ﬁve months .
On September 1, ABC News wrote that due to lack of evidence and increase in reports related to ivermectin toxicity, the American Medical Association, American Pharmacists Association and American Society of Health-System Pharmacists had called for an ‘immediate end’ to prescribing, dispensing or using the deworming drug ivermectin to treat or prevent COVID-19 .
On September 1, Washington Post wrote that people using ivermectin for prophylaxis had been shocked about having ended up being hospitalized for COVID-19 . The story mentioned the rise in prescriptions and FDA’s tweet and warned about overdoses. Numerous interviewees advised against ivermectin, with the most critical comparing it to ‘snake oil’. Overall, a part of the population preferring ivermectin and vitamin cocktails over vaccines was seen to indicate ‘a broader problem: a public health crisis made worse by many people’s distrust of medical authorities while they rely on often faulty information from some ofthe country’s most inﬂuential people, which is ampliﬁed through social media’. Ivermectin was said to have gained particular traction in conservative circles. Wagshul of the FLCCC was quoted saying that ivermectin was more eﬀective than vaccines against variants given waning immunity. A researcher working on an ongoingclinical trial on ivermectin in the US ([225,226]) commented that ‘there’s either people that believe it totally is a cure-all and works or that it is highly dangerous . . . and the reality is, neither extreme is true’.
On September 1, a letter by Keehner et al. in the New England Journal of Medicine reported about a dramatic decline in vaccine eﬀectiveness from June to July in a highly vaccinated health system workforce in California, likely due to the emergence of the delta variant, waning of immunity over time, and the end of masking requirements in California .
On September 1, KFOR News published a news story in which a rural Oklahoma doctor, Jason McElyea,claimed that local emergency rooms were so backed up with patients having overdosed ivermectin that gunshot victims had hard time getting to the facilities . In addition, ivermectin overdose patients were completely clogging ambulance services: McElyea was quoted saying that ‘all of their ambulances are stuck at the hospital waiting for a bed to open so they can take the patient in and they don’t have any, that’s it. . . if there’s no ambulance to take the call, there’s no ambulance to come to the call’.
On September 1, 2021 the subreddit r/ivermectin was ‘quarantined’ by the Reddit platform but that did notstop the ﬂood of oﬀensive posts. Alternative forums were created but they seemed to fail to capture largeaudiences (e.g. ). Another subreddit, r/IVMScience appeared to have stalled after August 23, 2021,with the moderator’s account deleted.
On September 1, podcaster Joe Rogan, with 11.1 million followers on YouTube, 13.2 million followers on Instagram and a USD 100 million contract to publish his podcast exclusively on Spotify, revealed on Instagram that he had got COVID-19 and had been treated with monoclonal antibodies, ivermectin, azithromycin, prednisone, nicotinamide adenine dinucleotide drip and a vitamin drip for three days in a row . Rogan’s statement was widely taken up by news media [231,232,233]. On July 1, 2021, in the context of an unrelated controversy, a journalist at the New York Times had called Rogan ‘too big to cancel . . . one of the most consumed media products on the planet – with the power to shape tastes, politics, medical decisions’ .
On September 1, a letter to the editor by Bryant et al. commented on the recent report in the Guardian discussing the eﬀect of the removal of the Elgazzar et al. trial on the meta-analysis by Bryant at al. .
The authors stated that ‘while quantitative measures of eﬀect do of course change on removal of any study,the overall ﬁndings of a signiﬁcant mortality advantage in ivermectin treatment, and in prophylaxis, remain robust to removal of the disputed data. The claim that conclusions are “entirely reversed” cannot be sustained on the evidence’ .
On September 1, Due˜nas-Gonz´alez et al. discussed repurposing of ivermectin as a novel anticancer .
On September 2, Newsweek published a version of McElyea’s story, saying people taking the horse de-wormer medication were ﬁlling up the area’s emergency rooms . The report mentioned FDA’s ‘stern warnings’against ivermectin, the unavailability of ambulances, and gunshot victims’ diﬃculties.
On September 2, Rolling Stone wrote about how Joe Rogan ‘became a cheerleader for ivermectin . . . no one has been more successful at promoting ivermectin than Rogan’ .
On September 2, a major Finnish newspaper Helsingin Sanomat republished a news article written by Finnish News Agency (STT) about an US podcast host Joe Rogan treating his COVID-19 infection with a ‘dewormer intended for horses’ warned against by ‘medical oﬃcials’ . The article described that after his diagnosis Rogan begun taking ‘all kinds of potions’ including ivermectin, which, according to Washington Post and the Guardian, was used as a dewormer for horses. However, ‘some representatives of conservative media’had ‘advertised the controversial dewormer’. In addition to mentioning the negative stance of the European
Medicine Agency (EMA), the article also cited FDA’s tweet saying: ‘You are not a horse. You are not a cow.
Seriously, y’all. Stop it’. According to the article, calls about ivermectin exposure to poison control centers in the US jumped to ﬁve times over normal levels in July 2021. Rogan was also described having spread ‘lies’about COVID-19 and being against vaccines. The leading infectious diseases expert Anthony Fauci was said to have criticized Rogan’s earlier statements. Up to the 1990s, STT, founded in 1887, was often consideredt he ‘oﬃcial’ national news source. Helsingin Sanomat, the most widely distributed newspaper in Finland,essentially holds a monopoly in the metropolitan area. The article was also republished by the most widely distributed yellow press media Ilta-Sanomat belonging to the same concern as Helsingin Sanomat . In addition, the story was posted in some regional newspapers , essentially reaching the whole population of the country.
On September 2, a competing Finnish yellow press newspaper wrote about Rogan’s use of dewormer, saying that it had no proven eﬃcacy and it could be dangerous, even deadly . Rogan was said to regularly ‘ﬂirt with misinformation’. The article also described FDA warnings and retraction of the Elgazzar et al. trial.
On September 2, citing insuﬃcient evidence of eﬃcacy, leading health experts in Sri Lanka urged people to stop using ivermectin for COVID-19; however, a local trial was ongoing .
On September 2, Marik and Kory published a reanalysis of the data of their earlier meta-analysis ,saying that the summary point estimates were largely unaﬀected when the study by Elgazzar et al. was removed .
On September 2, a letter to the editor by Neil et al. said that their Bayesian analysis provided suﬃcientconﬁdence that ivermectin was an eﬀective treatment for COVID-19, also after the exclusion of Elgazzar et al. study .
On September 2, a Cochrane review concluded that the authors were uncertain whether the investigational monoclonal antibody sotrovimab had an eﬀect on mortality (RR 0.33, 95% CI 0.01-8.18) and invasive mechanical ventilation requirement or death (RR 0.14, 95% CI 0.01-2.76). Treatment with sotrovimab was said to possibly reduce the need for oxygenation (RR 0.11, 95 % CI 0.02-0.45), hospital admission or death by day 30 (RR 0.14, 95% CI 0.04-0.48) .
On September 2, an article by Alves et al. in the BMJ about poorly designed studies contributing to misinformation in Brazil said that ’much like a poorly written sequel to a blockbuster, the ivermectin narrative appears to be a subsidiary of the rationale that gave the world the HCQ pseudo-solution to COVID-19: cheap, readily available answer to the biggest sanitary crisis of our time’ . The authors argued that public communication of science (i.e. news reporting) should be evidence based: any interaction between scientists and press should aim at summarizing and contextualizing the most important ﬁndings of an article for the general public, preserving context and limitations of the research, promoting transparency,integrity and scientiﬁc literacy. Also, research ﬁndings should be published without delay and include full datasets. Otherwise, the authors said, public communication may be only fueling polarization and an eventual implementation of harmful, ineﬃcient or wasteful public health policies.
On September 2, an article by Chaudhry et al. presented a systematic review about the role of ivermectin in hospitalized patients .
On September 2, a report in BuzzFeed news questioned the validity of two prophylaxis trials by Carvallo etal. in Argentina . The report claimed that the reported numbers, genders and ages of trial participants had slight inconsistencies. Carvallo was said to have declined to share the raw data even to his coauthors, the timeline and ethical approvals of the trials were unclear, as well as who had performed the statistical analyses.
It was also unclear which hospitals had been involved and in which ways. Carvallo denied accusations of fraud.
On September 3, an article by Okogbenin et al. described a retrospective study in Nigeria, with 300 patients treated with ivermectin, zinc, vitamin C and azithromycin, reporting zero mortality .
On September 3, a rapid response by Bryant et al. to Popp et al.  stated that their Bryant et al. metaanalysis was a non-commissioned research paper that strictly followed PRISMA systematic review guidelines,and that Popp et al. itself contained several misleading items, including using death instead of infection for the prophylaxis outcome, specifying outcome measures not found in the included trials but ignoring the outcome measures found in the trials, subsequently stating that they found ‘no data’ . The authors concluded that in a pandemic context, the beneﬁts of ivermectin almost certainly outweighed any risks.
On September 3, a blog post by Meyerowitz-Katz discussed the study by Carvallo et al. , pointing outissues that indicated possible fraud, yet noted that the study was not a randomized controlled trial and thus
not included in most meta-analyses or given the same credence, and it did not change recommendations foroﬃcial medical organizations. However, Meyerowitz-Katz added, ’it perhaps had an even bigger impact onpeople actually taking ivermectin than previously fraudulent research. This paper showed a 100% beneﬁt,it was enormously popular on social media, and it was given a huge amount of credence by promoters ofivermectin for nearly a year. It is not a stretch to say that this one study has perhaps caused hundreds ofthousands or even millions of people to take ivermectin as a prophylactic drug to prevent COVID-19’ .
On September 3, South African Health Products Regulatory Authority (SAHPRA) repeated its warnings against the use of ivermectin, saying its stance was aligned to that of US FDA .
On September 3, Yahoo News published a version of McElyea’s story, mentioning that he was an emergency room physician aﬃliated with multiple hospitals in Sallisaw, Oklahoma, and that the situation was so dire that even people with gunshot wounds have to wait their turn to get treatment . McElyea added that people were suﬀering real ramiﬁcations from taking a dosage meant for a full-sized horse, including ‘scary’instances of vision loss, nausea, and vomiting.
On September 3, Rolling Stone magazine published a version of McElyea’s story .
On September 4, the Guardian published a version of McElyea’s story .
On September 4, BBC published a version of McElyea’s story .
On September 4, the administration of Northeastern Health Systems (NHS) Sequoyah posted a statement saying that although McElyea was not an employee of NHS Sequoyah, he was aﬃliated with a medical staﬃng group that provided coverage for the emergency room at Sallisaw but he had not worked there in over two months [259,260]. The administration clariﬁed that NHS Sequoyah had not treated any patients due to complications related to taking ivermectin, including not treating any patients for ivermectin overdose. They added that all patients who had visited the emergency room had received medical attention as appropriate,and the hospital had not needed to turn away any patients seeking emergency care.
On September 4, KXMX interviewed a hospital administrator of NHS Sequoyah who stated that the hospital being overloaded by ivermectin patients was ‘simply not the case in Sallisaw .. . we have not seen or had anypatients in our ER or hospital with ivermectin overdose . . . we have not had any patients with complaints or issues related to ivermectin . . . we are not overrun with patients with ivermectin related issues’ .
The administrator added that McElyea had treated patients in the Sallisaw emergency room but not in the past several months, and added that she wanted the public to know that McElyea did not speak for NHSSequoyah.
On September 4, NPR wrote that poison control centers are ﬁelding a surge of ivermectin overdose calls [262,263].
On September 4, Reuters published a fact-check article saying that ‘outrage has spread online that Afghan refugees entering the United States will receive the drug ivermectin although it does not have U.S. approval as a COVID-19 treatment. However, the posts miss the vital context that refugees are given ivermectin for infections unrelated to the novel coronavirus . . . ivermectin is administered as a presumptive treatment forintestinal parasite’ . The ‘outrage’ was said to have been caused by ivermectin being administered to refugees but being largely unavailable for US citizens willing to use it for COVID-19.
On September 4, an article by Associated Press published in Indian Express said that eﬀorts to stamp out use of parasite drug ivermectin for COVID-19 in US were growing . It said that ivermectin was being‘promoted by Republican lawmakers, conservative talk show hosts and some doctors, ampliﬁed via social media to millions of Americans who remain resistant to getting vaccinated’, with the American Medical Association, two US pharmacist groups, FDA, CDC and WHO advising against it.
On September 5, the Guardian added an amendment to the end of their article, quoting parts of the statementby NHS Sequoyah, saying that the hospital had not treated any patients related to taking ivermectin,including overdose .
On September 5, a ‘fact check’ by Shore News Network called the McElyea story ‘completely false’, mentioning that the publishers had not issued retractions, saying that ‘the left continues to push a media narrativethat conservatives and Republicans are creating an ivermectin health crisis’ .
On September 6, a preprint by Buonfrate et al. described randomized controlled trial in Italy with results indicating statistically insigniﬁcant dose dependent viral load reduction (NCT04438850) . The authors said that ivermectin remained safe with dosing regimes of 0.6 mg/kg and 1.2 mg/kg for ﬁve days. The study was terminated early due to lack of eligible patients.
On September 6, a blog post by an US doctor working on new models for mental health care called theMcElyea story ‘too good to check’, saying that ’the media has tried to spread the word that the scientiﬁc consensus [about ivermectin for COVID-19] remains skeptical. In the process, they may have gone a littleoverboard and portrayed it as the world’s deadliest toxin that will deﬁnitely kill you and it will all somehow be Donald Trump’s fault’ [269,270].
On September 6, a report by News On 6 said ‘a false report has Oklahoma trending nationally . . . the doctor at the center of the story told News 9 he was misquoted, and the story was wrong’. McElyea clariﬁedthat ‘as the story ran, it sounded like all of Oklahoma hospitals were ﬁlled with people who have overdosed on ivermectin and that’s not the case, . . . the cases we are seeing, people who are overdosing on ivermectin,they are taking full strength cattle doses and coming in and that is something that could be avoided’.
The report mentioned another hospital in the area, Integris Grove, having stated that they had seen ‘a handful of ivermectin patients in their emergency rooms . . . while our hospitals are not ﬁlled with people who have taken ivermectin, such patients are adding to the congestion already caused by COVID-19 and other emergencies’. The report concluded with a mention that the Oklahoma Center for Poison and Drug Information had received 12 ivermectin-related calls last month .
On September 6, Soave analyzed the media reporting, saying that the media fell for a viral hoax about ivermectin overdoses straining rural hospitals . He commented that McElyea clearly stated that ivermectin overdoses were a problem and claimed that some hospitals were dealing with strain in general but he neveractually connected these two issues. Instead, the KFOR’s journalist had added that framing; she had notresponded to a request for comment. If other media outlets had called the doctor or the hospitals they would have easily uncovered the error. Soave added that while the mainstream media had vigorously condemned COVID-19 misinformation in social media, readers could also encounter it in mainstream media such as Rolling Stone, New York Times or Associated Press (AP) which had recently reported that 70 percent of calls to Mississippi’s poison hotline were from people who had taken ivermectin while the actual ﬁgure was 2 percent  (AP was a member of the Trusted News Initiative (TNI) ).
On September 6, another judge reversed the earlier decision concerning administration of ivermectin prescribed by Wagshul to a patient in a US hospital, saying there ‘was no doubt that the medical and scientiﬁc communities do not support the use of ivermectin as a treatment for COVID-19’ . The judge addedt hat ‘COVID-19 has ravaged the world. However, the rule of law must be followed once the court system is involved. The law in its purest form shall have neither hatred nor sympathy to anyone or anything. It shall stand unwavering in its truth, justice, and fairness to call’ . A spokesperson for the hospital described the ruling as ‘positive in regards to the respect for science and the expertise of medical professionals’, adding that they implore the community ‘to do what we know works: wear a mask, become fully vaccinated and use social distancing whenever possible’. She added that the hospital appreciated scientiﬁc rigor and did not believe they should be ordered to administer medications ’against medical advice’.
On September 6, a German magazine for pharmacists reported about American Pharmacists Association’s recent demand to stop oﬀ-label ivermectin prescribing . The article mentioned the ongoing PRINCIPLEtrial by University of Oxford.
On September 7, Fox News reported that McElyea was an employee of an agency that staﬀs emergencydepartments . The report also mentioned that while NHS Sequoyah had stated they had not treatedany ivermectin patients, Integris Grove Hospital, had seen a handful’. Integris added that ‘there is a lotof media attention surrounding remarks reportedly made by Dr. McElyea. While we do not speak on hisbehalf, he has publicly said his comments were misconstrued and taken out of context’.
On September 7, a CNN reporter Daniel Dale tweeted about McElyea case, saying local media had misrepresented the interview of McElyea, national and international media had failed to do due diligence, and readers and critics had jumped to conclusions. He concluded that ‘lots of people involved here – certainly the local outlet/the big aggregating outlets/the prominent tweeters on the left, but also some critics on the right – could’ve done a better job pursuing facts/waiting for facts before coming to conclusions’ . CNN published a ‘fact-check’ report with similar content .
On September 7, an Austrian newspaper wrote that the misconception that horse dewormer ivermectin wouldhelp against COVID-19 is widespread internationally and also in Austria . The article mentioned thatno poisonings had been reported in Austria, and that Czech Republic had adopted ivermectin in hospitals.
A toxicologist commented that ivermectin was still dangerous and there was insuﬃcient data on the safety of chronic consumption.
On September 7, the title of a January 2021 article in a German women’s magazine, originally asking whether ivermectin might be useful, was updated to ‘People are not horses’ .
On September 7, a Swedish newspaper Svenska Dagbladet wrote that instead of being vaccinated Americans are taking ivermectin as the latest alternative treatment for COVID-19, the only problem being that it was intended for treating parasites in horses and cows .
On September 7, Joe Rogan complained that CNN had reported that he had been taking ‘horse dewormer’;Rogan stated that ‘I literally got it from a doctor’ .
On September 7, wealthy Chinese exile Guo Wengui was said to be using his online misinformation network to promote the use of unproven treatments for COVID-19 .
On September 8, an article by Cruciani et al. presented a systematic review and meta-analysis of ivermectin for prophylaxis and treatment of COVID-19 . Based on an analysis of eleven RCTs, the authors concluded that there was limited evidence for the beneﬁt of ivermectin.
On September 8, a letter published in the Guardian by Hill, the main author of one of the meta-analyses about ivermectin , said that after his team had questioned the clinical beneﬁts of ivermectin the team and his family had received daily death threats. As social media platforms had not reacted he had stopped using social media but abuse by email had continued. Hill described the situation as shocking, aﬀecting many scientists, and said that scientists must be protected from anti-vaxxer abuse, possibly by police action .
On September 8, Wired magazine wrote about Together trial results, quoting the head researcher saying that ivermectin proponents had ignored their ﬂuvoxamine ﬁndings, only being interested in ivermectin,‘feeling strongly’ about it but not about other possible options . The article also mentioned US NIH’s ongoing ACTIV-6 ivermectin trial, into which people could sign up at home. A co-chair of the trial’s steering committee said that there was no data on ivermectin’s beneﬁt but since people were using it, the point of their trial was to get a deﬁnitive answer.
On September 8, the Guardian worried about some Australian clinics’ oﬀ-label prescribing of ‘unapproved’ivermectin . The president of the Royal Australian College of General Practitioners (RACGP) said that while RACGP did not consider its role to be looking over the shoulders of every GP, the advice from the health experts to not use ivermectin was ‘100% clear’. However, she added, ‘the status of other drugs, suchas sotrovimab, is very diﬀerent. That is an example of a new drug for the treatment of Covid-19 that haspassed through the rigorous testing safety procedures of the Therapeutic Goods Administration’.
On September 9, Geert Vanden Bossche summarized the negative eﬀects of mass vaccination as follows: itwill, ﬁrst, eventually drive dominant propagation of super variants that are highly infectious and increasinglyresist vaccine-induced neutralizing antibodies; second, erode innate immune defense in the non-vaccinated(due to high infectious pressure exerted by enhanced circulation of more infectious variants); and third,erode naturally acquired immunity (due to increasing viral resistance to neutralizing spike protein speciﬁcantibodies). Of these, the second and third consequences together prevent herd immunity from being established.
Yet the solution, according to Bossche, would be induction of herd immunity by starting from scratch against the more infectious variants. This could be achieved by providing multidrug early treatment for the infected which would result in enhanced rates of recovery from disease and rise in the number of people who develop life-long protective immunity. Also, mass antiviral treatment with any drug that would eﬀectively reduce viral infectious pressure would be required to prevent innate antibodies in previously asymptotically infected individuals from being suppressed by short-lived, spike protein speciﬁc antibodies and thus enable the healthy, unvaccinated part of the population to deal with all SARS-CoV-2 variants; these massantiviral campaigns might need to include pets and live-stock and be combined with lockdown rules foras long as titers of these short-lived antibodies were measurable (6-8 weeks).
Boscche said that a larger unvaccinated population would circulate also less infectious variants, attenuating circulation of more infectious variants. However, the above methods would still be unlikely to suﬃciently reduce transmission among healthy individuals; therefore ultimately an immune intervention able to prevent infection in all susceptible age groups would be required, and as long as such an intervention, likely based on natural killer cell based vaccines, would not be available, repeated antiviral chemoprophylaxis might be necessary. However, as along term strategy the chemoprophylaxis would not be feasible, as overuse could promote viral resistance to the compound.
About his personal intentions Bossche wrote that ‘one can always do more, write morearticles, bring more scientiﬁc evidence to the table, do more interviews and podcasts, reply to more questionsand destroy more of the nonsense divulgated by scientiﬁcally incompetent experts or illiterate fact-checkers.
However, I’ve decided to not continue along this path as I knew from the very start that this big alliance of stakeholders would not listen and as the primary purpose of my endeavors has always been to share, as broadly as possible, my scientiﬁc insights on why this [mass vaccination] experiment is an incredible blunder, so that none the involved experts, key opinion leaders, public health authorities or peers from industry could ever pretend that this was unknown and simply unpredictable’ .
He said that he had a history of going against ‘groupthink’, for example speaking against the results of Gavi The Vaccine Alliance’s phase III Ebola vaccine trials conducted by the World Health Organization (WHO) and published in a peer-reviewed journal. Bossche said the results falsely concluded that the vaccine had 100% eﬃcacy, whereas according to Bossche’s analysis ‘the truth looked extremely diﬀerent’ . He added that to him it seemed that ‘many of our experts and scientists, even including a substantial number of renowned professors, are so stuck within their small silos that they have simply lost touch with reality’.
On September 9, Hill responded to a tweet by the BIRD group which had said that according to Hill, the conclusions of the meta-analysis by Hill et al. remain clearly in favor of ivermectin even after exclusion ofElgazzar et al. trial [292,293]. Hill stated: ‘Misleading information from the BIRD group. In our analysis there is no signiﬁcant survival beneﬁt for ivermectin in randomized trials after exclusion of apparently fraudulent and biased studies’ . Later on the same days he responded with ‘more misleading information from the BIRD group misquoting our research’ to another tweet by the BIRD group which had said that‘Hill’s work also shows that ivermectin not only reduces the risk of death, it clears the virus from the bloodstream faster than controls, thus ivermectin reduces the time that an infected person can transmit the virus’ .
On September 9, Joe Rogan discussed the ‘horse dewormer’ narrative, referring to regulatory capture in theUS .
On September 10, a news report in the BMJ discussed US court rulings and ivermectin prescriptions .
On September 10, the BIRD group announced that their meta-analysis by Bryant et al.  had reached a position in the top ten of 18.9 million articles tracked by Altmetric [297,298].
On September 10, Hill tweeted that the ‘survival beneﬁt of ivermectin disappears when only trials at low risk of bias are analyzed. The reported survival eﬀects are entirely driven by studies at high risk of bias or medical fraud’ . An accompanying graph indicated slightly over 50% beneﬁt (p=0.01) with Elgazzar et al. study included, slightly under 40% beneﬁt (p=0.05) without it but including studies with a high risk for bias, and approximately 4% beneﬁt (p=0.90) with only low risk studies included.
On September 10, a blog article discussing failed communication attempts between ivermectin skeptics and proponents commented that ‘what you are witnessing is just the most absurd example of a decades-long war on re-purposed (aka “non-proﬁtable”) medicines’ [300,301,302].
On September 10, Hindustan Times wrote about a clinical trial (RIVET-COV) with 157 patients with mild to moderate disease carried out by All India Institute of Medical Sciences (AIIMS) which indicated that ivermectin did not reduce the viral load or duration of symptoms . Mohan said that ‘all the ivermectin being prescribed or being taken by people left, right, and centre will deﬁnitely not show any eﬀect’; therefore ivermectin should not be used outside clinical trials, although he added that their trial did not investigate possible eﬀect on mortality.
On September 11, TrialSite News wrote about US NIH’s refusal to release information on who had been involved in its decision to recommend neither for nor against ivermectin . However, US CDC had released the names of the members of the working group . According to TrialSite News, three of the nine members, Adimora, Bedimo and Glidden, had disclosed a ﬁnancial relationship with Merck & Co/MSD.
Another member, Naggie, had later received USD 155 million funding for US NIH’s ACTIV-6 trial which included ivermectin, ﬂuvoxamine and ﬂuticasone (NCT04885530) .
On September 11, TrialSite News wrote that Australia’s Therapeutic Good Administration (TGA) had formally placed a national prohibition on oﬀ-label prescribing of ivermectin to all general practitioners,citing interruption of vaccination as a factor in the decision .
On September 12, a three-day International Covid Summit started in Rome [308,309], with presentationsin the Roman Senate held also in Italian and Spanish and translated into sign language. Lecturers included Roberta Ferrero, Francesca Donato, Albert Bagnai, Luigi Icardi, Ivan Vilibor Sincic, Joseph Tritto, Robert Malone, Mauro Rango, Christof Plothe, David Anderson, Ira Bernstein, Fabio Burigana, Steven Hatﬁll,Roberto Accinelli, Tess Lawrie, Oswaldo Castaneda, Rosanna Chifari, Antonietta Gatti, Andrea Stramezzi, Peter Mccullough, George Fareed, Pierre Kory, Roberta Lacerda, Carlos Maggi, Bruce Patterson, DilipPawar, Victor Villa, Mattia Perroni and Francesco Matozza. In addition, the summit featured groups of researchers and clinicians from Italy, Croatia, Czech Republic, Poland, Romania, Bulgaria, Tanzania, South Africa, Nigeria, Mali, Spain, UK, France, Brazil, Bolivia, Argentina, Paraguay, Peru, Canada and US. Several treatment protocols including McCullough et al’s sequenced multidrug protocol  and FLCCC’s MATH+protocol were discussed.
On September 13, a Dominican Republic newspaper described details of an early 2020 ivermectin trial by Morgenstern et al. [311,312].
On September 13, a story in Rolling Stone ridiculed ‘anti-vaxxers’ for using povidone iodine mouthwash to prevent COVID-19 . An interviewed gynecologist/obstetrician commented that ‘we use it before surgery to clean the vagina’ and that ‘it could result in iodine poisoning if taken orally’. Another physician who appeared unable to give statements without including profanities in his sentences commented that ‘drinking iodine’ had caused a patient a transient kidney failure and that povidone iodine deﬁnitely could not reducethe eﬀects of COVID-19 or prevent its transmission. An ’Australian family physician’ stated that ‘there have been no human studies on the use of Betadine to treat COVID-19, just hypotheses and lab studies’.
On September 13, the Guardian wrote about ‘ivermectin frenzy’ being ‘a cottage industry of advocacy groups, anti-vaccine activists and telehealth companies’ despite stances of FDA, NIH and some US medical and pharmaceutical associations . It noted that FLCCC had signed open letters in favor of ivermectin which had also been signed by ‘anti-vaxx’ organizations. Telehealth sites were said to have connections to a conservative doctor group America’s Frontline Doctors in favor of hydroxychloroquine treatments and whose opinions had been quoted by ‘Donald Trump, his son Donald Trump Jr and numerous QAnon conspiracists’.
On September 13, Mother Jones magazine wrote that people associated with Q-Anon had harassed a hospital where a Q-Anon member had been hospitalized with hundreds of calls and emails, in order to get ivermectin administered to her .
On September 14, in a Cochrane Collaboration author interview, Stephanie Weibel and Maria Popp described their ivermectin meta-analysis . The authors said that because of a lack of good-quality evidence, it was unknown whether ivermectin reduces or increases mortality, caused adverse eﬀects, improved or worsened patients’ condition, or increased or decreased viral load, led to more or fewer negative COVID-19 tests 7days after treatment. Likewise, they could not say whether ivermectin prevented COVID-19 infection or reduced the number of deaths after high-risk exposure to the SARS-CoV-2 virus.
On September 14, Menichella wrote about Peter McCullough’s inﬂuence in Italy and about a protocol developed in Italy by a group led by Giuseppe Remuzzi . The Remuzzi protocol was mainly based on relatively selective COX-2 inhibitors . In a retrospective observational matched-cohort study with 90outpatients and 90 controls with mild disease the proportions of patients who required hospitalization were2% vs 14% (p=0.01); cumulative days of hospitalization were 44 vs 481 days, and costs of hospitalization were EUR 28,000 vs EUR 296,000, respectively. Menichella wrote that the standard of care resulted in approximately 2% mortality; with a ’serious home treatment protocol’ mortality could be lowered to 0.05%.
On September 15, an article by Talwar et al. described a case of a successful management of ivermectinpoisoning . A 6-year-old girl weighing 20.5 kg had accidentally consumed 600 mg of ivermectin (29.3mg/kg). Mechanical ventilation, ceftriaxone, clindamycin, intravenous midazolam, phenytoin and supportivemeasures were utilized. The girl was discharged after nine days of hospitalization.
On September 15, a news report in Willamette Week discussed US biologist Bret Weinstein’s role in the ivermectin controversy, including his inﬂuence on Joe Rogan .
On September 15, a letter to the editor by Boretti discussed quercetin, suggesting that quercetin might help to lower inﬂammation, as well as reduce the toxic eﬀects of COVID-19 vaccines and the chances of being infected . Quercetin had been included in the FLCCC protocols since early 2020.
On September 15, Fenton et al. discussed unreliability of current vaccine studies .
On September 16, Cheng et al. presented a meta-analysis about eﬃcacy and safety of various medications for treating severe and non-severe COVID-19 patients .
On September 16, Malhotra discussed Indian Bar Association’s legal notice to WHO .
On September 16, an Australian medical newspaper wrote that a secretive organization called the COVID19 Antiviral Advisory Group had said it had been instructing 200 doctors to prescribe ivermectin and was planning on going public against TGA’s ivermectin ban .
On September 17, an article by Singh et al. suggested a positive correlation between European populations’zinc suﬃciency status and COVID-19 mortality. The authors noted that the observed association was contrary to what would be expected if zinc suﬃciency was protective in COVID-19, suggesting that controlled trials or retrospective analyses of the adverse event patients’ data should be undertaken to correctly guidethe practice of zinc supplementation in COVID-19 .
On September 17, an article by Gurung et al. described an in silico study which indicated that ivermectin demonstrated moderate binding to human serum albumin .
On September 17, a preprint by Karale et al. presented an updated systematic review and meta-analysis of mortality, need for ICU admission, use of mechanical ventilation, adverse eﬀects and other clinical outcomes
. 52 studies (n=17,561) were included in a qualitative analysis and 44 of those (n=14,019) were included in the meta-analysis. A mortality meta-analysis indicated lower odds of death (OR 0.54, 95% CI 0.34-0.86,p=0.009, 29 studies). As adjuvant therapy, the odds of viral clearance were higher (OR 3.52, 95%CI 1.816.86, p=0.0002, 22 studies), the duration to achieve viral clearance was shorter (p=0.02, 8 studies), andthe need for hospitalization was reduced (OR 0.34, p=0.008, 6 studies). The authors concluded that themortality beneﬁt of ivermectin in COVID-19 is uncertain but as an adjuvant therapy ivermectin may improve viral clearance and reduce the need for hospitalization.
On September 17, a news report by Piper in Vox magazine questioned the validity of studies by Carvallo etal. [329,330], saying that experts on scientiﬁc fraud didn’t believe Carvallo conducted his study as described:the data appeared fabricated, key data was missing, study registration and published results didn’t match with each other, Carvallo could not explain these issues, and the hospital in which the study was said to have been conducted stated that it had not been conducted there, to which Carvallo replied that it had been but without the hospital administration knowing . In another context, Lawrie of the BIRD group had been asked what evidence would persuade her that ivermectin didn’t work, to which she had replied thatthere could be nothing that would persuade her. Mills involved in the Together trial commented that themost culpable parties weren’t those who had believed in the apparently fraudulent studies but those whohad conducted, published, and boosted them.
On September 17, Business Insider wrote about FLCCC’s Kory and Marik, calling them ’fringe doctors whipping up false hope that could have deadly consequences’ . According to Business Insider, Kory was’a once respected doctor whose hospital rejected his unsupported treatment ideas’ while Marik was ’a doctor who ostracized himself from mainstream medicine after his high-proﬁle sepsis treatment was a dud’, adding that ’Marik’s failed sepsis protocol later became the backbone of the FLCCC’s ﬁrst iterations of COVID-19treatment’ (the MATH+ inpatient protocol) . Recently they had been ’sucked (willingly or not) into the embrace of the anti-vaccine far right .. . ivermectin is now a darling drug of QAnon’. A former FLCCCmember, Eric Osgood, had left the group in summer 2021. The editor in chief of Science Communication said that FLCCC’s communication style was objectionable but added that the existence of ’rogue opinions’was a necessary condition for scientiﬁc breakthroughs. However not everyone had the skills to assess claimsnor understood how science worked, which had led to ’a conﬂict between our commitment to freedom of speech and a clash with the nature of scientiﬁc truth and people’s right to say anything they want . . . the hype machine they’ve created is out of control’.
On September 17, Seheult on MedCram reviewed ivermectin, with comments from cell biologist Rhonda Patrick . Seheult stressed the importance of taking all treatment options into account; Patrick said ivermectin had seemed to consistently reduce viral load but the hype around ivermectin was pushing researchers away from the subject.
On September 20, an Indian news agency reported that 31 of 75 districts of the state of Uttar Pradesh inIndia were COVID-19 free . In total, the state reported 17 new cases in the last 24 hours out of 182,742samples tested.
On September 20, the Guardian worried about horses being deprived of a deworming agent .
On September 21, Brazil’s president Bolsonaro stated that Brazil had supported clinicians’ early treatment measures since the beginning of the pandemic, adding that he could not understand why some countries opposed early treatment measures .
On September 21, Ars Technica discussed the validity of Covid Analysis group’s ivmmeta.com meta-analysis.
On September 22, a letter to the editor by Lawrence et al. in Nature Medicine concluded that metaanalyses based on summary data alone were inherently unreliable . The authors stated that most,if not all, of the ﬂaws in recent ivermectin meta-analyses would have been immediately detected if metaanalyses were performed on an individual patient data (IPD) basis. They recommended that meta-analysts who study interventions for COVID-19 should request and personally review IPD in all cases, even if IPDsynthesis techniques were not used. They also recommended that all clinical trials published on COVID-19should immediately follow best-practice guidelines and upload anonymized IPD. They authors said that their proposal was a change to a nearly universally accepted practice over many decades and substantially more rigorous than current standards; regardless, the proposed change was imperative.
On September 22, in a FLCCC weekly update, Marik announced an upcoming publication of an article on the pathophysiology of COVID-19 .
On September 22, a video by John Campbell described the contents of ivermectin kits used in state of Goain India . The kits in Goa contained pulse oximeter, a thermometer, paracetamol, vitamin C and D,multivitamin tablets containing zinc, ivermectin (10 x 12 mg), doxycycline (10 x 100 mg), and personal protective equipment. The cost of one kit was USD 2.65. The kits used in Uttar Pradesh contained ivermectin, doxycycline, vitamins B, C and D, zinc, paracetamol, thermometer and a pulse oximeter. Outpatients weremonitored by phone twice a day. Campbell said that the intervention had actually been organized under a WHO monitoring program. A WHO report described that since May 5, 2021, 141,610 government teams were moving across 97,941 villages in 75 districts over ﬁve days in Uttar Pradesh, a state with a population of 230 million . WHO ﬁeld oﬃcers monitored over 2,000 government teams and visited at least 10,000 households. WHO also said it was to support the Uttar Pradesh government on the compilation of the ﬁnal reports; these reports had not yet been published.
On September 23, a preprint by Mayer et al. described an intervention program of high-dose ivermectin in COVID-19 carried out by the Ministry of Health of the Province of La Pampa, Argentina . Within ﬁve days of symptoms onset, 0.6 mg/kg/day of ivermectin for ﬁve days was administered. Active pharmacosurveillance was performed for 21 days, with hepatic laboratory assessments performed in a subset of patients. From 21,232 subjects with COVID-19, 3,266 were oﬀered and agreed to participate in the ivermectin program. 17,966 did not participate and were considered as controls. A total of 567 participantsreported 819 adverse events; 3.13% discontinued ivermectin due to adverse events. Mortality was lower in the ivermectin group in the full group analysis (1.5% vs 2.1%, OR 0.720, p=0.029), as well as in subjects over 40year-old (2.7% vs 4.1%, OR 0,655, p=0.005). ICU admission was signiﬁcantly lower in the ivermectin groupcompared to controls among participants over 40 year-old (1.2% vs 2.0%, OR 0.608, p=0.024). According to Covid Analysis group , in a full group analysis the unadjusted risk of death was 27.6% lower (RR 0.72,p=0.03) and unadjusted risk of ICU admission was 26.0% lower (RR 0.74, p=0.13).
On September 23, several groups of clinicians in favor of early treatments announced a new organization,World Council for Health, an umbrella organization with over 45 aﬃliated organizations . The council released a home treatment guide with a combination protocol consisting of vitamins C and D, zinc, quercetin, melatonin, ivermectin, mouthwash, ibuprofen, N-acetylcysteine, antihistamines, aspirin, and others .
The protocol was one of the ﬁrst ones to tentatively include iodine (Lugol’s solution).
On September 23, the Indian Council of Medical Research (ICMR) dropped ivermectin and hydroxychloroquine from clinical guidelines for the management of adult COVID-19 patients [347,348,349,350].
On September 23, a fact-checking website discussed social media posts claiming that ’ivermectin apparently sterilizes the majority (85%) of men that take it’ and a news report claiming that ’ivermectin causes sterilization in 85 percent of men, study ﬁnds’ [351,352].
On September 24, the Guardian wrote about misinformation spreading globally .
On September 24, the Guardian wrote about fraudulent ivermectin studies .
On September 24, Mashable interviewed ex-FLCCC member Osgood who said that he had initially joined the FLCCC because they were ’forward thinking doctors who were able to get ahead of the profession’ on a few hospital treatments (e.g. the use of anticoagulants) but he had left the organization because of his view that FLCCC insisted on promoting ivermectin over vaccines . He referred to povidone iodine prophylaxis of COVID-19 as misinformation.
On September 26, an article by Marik et al. presented a scoping review of the pathophysiology of COVID-19. The article described severe COVID-19 as one of the most complex of medical conditions known to medical science, noting that an overarching and comprehensive understanding of its pathogenesis, a requirement for the formulation of eﬀective prophylactic and treatment strategies, was still lacking. Threebasic pathologic processes were identiﬁed: a pulmonary macrophage activation syndrome with uncontrolled inﬂammation, a complement-mediated endothelialitis together with a procoagulant state with a thromboticmicroangiopathy, and platelet activation with the release of serotonin and the activation and degranulation of mast cells contributing to the hyper-inﬂammatory state (quercetin had been a part of FLCCC protocols sinceMarch 2020; in one study, it was found more eﬀective than cromolyn in blocking mast cell cytokine release). The article also mentioned the C-C chemokine receptor type 5 (CCR5) pathway which interacts with chemokine ligand 5 (CCL5 or RANTES).
On September 26, in a discussion with Robert Malone, Geert Vanden Bossche stated that the proper way would have been to vaccinate vulnerable groups only, and mentioned ivermectin chemoprophylaxis as a possible solution .
On September 26, the New York Times interviewed the acting head of the New Mexico (US) state health department who claimed that ivermectin ’had contributed to’ deaths of two hospitalized patients who had previously self-medicated with ivermectin ’instead of proven treatments like monoclonal antibodies’ .
On September 27, in a discussion with Anmol Ambani and Peter A. McCullough, Marik presented the contents of the new article in a video lecture .
On September 27, 5,200 doctors had signed a Global Covid Summit related ’Rome declaration’ .
On September 27, an article by Deng et al. presented a systematic review and meta-analysis about the eﬃcacy and safety of ivermectin . Based on an analysis of three observational studies and 14 RCTs representingvery low to moderate quality of evidence, the authors concluded that ivermectin was not eﬃcacious atmanaging COVID-19.
On September 28, an article by Barkati et al. concluded that corticosteroid therapy was an important risk factor for Strongyloides hyperinfection but there were challenges associated with the performance, availability and quality of Strongyloides tests. The authors concluded that presumptive use of ivermectin was reasonablein selected situations .
On September 28, an article by Zhang et al. presented a Bayesian network meta-analysis of 222 randomized controlled trials with 102,950 patients, suggesting that imatinib, intravenous immunoglobulin andtocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinanthuman granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance . On a treatment class level, the analysis found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates.
On September 28, the New York Times wrote that Facebooks groups promoting ivermectin continued to ﬂourish .
On September 28, a rapid review by Cardwell et al. about pharmacological interventions to prevent COVID19 mentioned ivermectin prophylaxis trials .
On September 29, a preprint by Budhiraja et at. described secondary infections in hospitalized patients inNorth India, mentioning that 43.5% of the patients had been administered ivermectin .
On September 29, referring to FLCCC, BIRD and America’s Frontline Doctors (AFLDS), Scientiﬁc Americanwrote about fringe doctors’ groups promoting ivermectin for COVID despite a lack of evidence .
On September 29, Chemistry World wrote that ivermectin debacle had exposed ﬂaws in meta-analysis methodology . The report stated that ’the people who’ve done these meta-analyses haven’t stuﬀed up. . . they haven’t deviated from accepted standards or made big mistakes . . . instead, there is a fundamentalﬂaw in the approach’.
On September 29, the Hill, the largest independent political news site in the US, wrote that ivermectin disinformation had led to new kinds of chaos .
On September 30, a preprint by Schaﬀer et al. describing changes in dispensing of medicines proposed for re-purposing in the ﬁrst year of the COVID-19 pandemic in Australia noted that there had a small but sustained increase in ivermectin dispensing between March 2020 and November 2020 .
On September 30, an introduction to Popp et al.’s Cochrane review by Jordan said that at this stage there were very few completed well conducted studies about either prevention or treatment but 31 trials were underway .
On a closer look it appeared that the quality of some early ivermectin trials had been lower than assumed.
As individual patient data had not been generally available, most parties including various groups publishing meta-analyses had implicitly trusted the summary data and ignored slight inconsistencies. The current best practice guidelines did not require analysis of individual patient data. The proposal that meta-analyses should be performed on individual patient data appeared justiﬁed. An additional, likely necessary change to methodology would be adoption of the do-search method, assumedly the most general tool currently available for causal eﬀect identiﬁcation, and as such an improvement over Bayesian methods [179,373].
In 2014, Every-Palmer et al. noted that little ‘high quality’ (according to evidence-based medicine standards)empirical evidence existed that EBM should beneﬁt the population, i.e. evidence about EBM’s superiority in improving patient outcomes . In 2018, Anjum claimed that EBM relied on a ﬂawed positivist methodology . Recently, Martini claimed that the concept of evidence was insuﬃciently deﬁned .
A fundamental error appeared to be the insistence on trialing single agents instead of combination protocols.
All of the currently utilized early treatment protocols were combination protocols and it was unlikely that the same results could have been obtained with a single agent. Thus, combination protocol trials would have been more likely to produce statistically signiﬁcant eﬀects. The insistence on large trials, instead of eliminating biases, possibly introduced them. For example, a lack of funding for repurposing may have introduced a severe funding-related bias.
It appeared that prolonged stress and continuing unpredictability of the situation had overwhelmed many,occasionally leading to actions whose consequences were perhaps badly thought out. The situation seemedto amplify preexisting tendencies and weaknesses within groups, leading to group-speciﬁc biases, formationof subcultures, or variants of ’groupthink’ . Groups suspecting the pharmaceutical industry, authoritiesand ’the mainstream’ seemed to amplify these tendencies in-group, whereas groups suspecting anything’fringe’ but favoring mechanistic thinking and overreliance on speciﬁc methods or paradigms seemed toamplify these tendencies. Groups with a tendency to act out in panic or anger exhibited that behavior,while groups with a tendency to retreat into fearful inaction and silence did that. The central role of trustwas highlighted, yet trust seemed practically nonexistent.
Also strengths were exhibited, most prominently the capability of forming groups and alliances. However,these groups tended to become tribal in their nature, and the result resembled tribal warfare, a practice that the humanity should already have transcended. It seemed as if everyone was trying to take care of others in their own ways but these ways were incompatible with each other; someone once deﬁned conﬂicts as ’failed attempts to love’.
It also seemed that journalists and the public had an idealized image of science and were trying to ﬁnd solace in it as in a religion, with some scientists maybe trying to maintain these illusions. One commentator noted that ’society was not ready to watch science in real time’ . Another added that ’science was not prepared to display itself to the public in real time’, while a third said that ’society was not ready to watch science in any other way either’.
In the news media, emotionally manipulative tactics seemed common. A prime example of arrogance and lack of due diligence was the case of Rolling Stone ridiculing povidone iodine use , claiming that there had been no human trials about it on COVID-19, despite the fact that there had been several, with promising results [10,378,379,380,381] (for observational studies, see e.g. [382,383]; for an updating list, see ).
Ways of reasoning appeared incompatible for example in the case of the Guardian’s critique of the BIRD group aﬃliating with organizations labeled as anti-vaccine for the purposes of promoting early treatment.
In the view of the BIRD group founder, vaccinations were unrelated to early treatments and, subsequently,the vaccination stances of the aﬃliates irrelevant. While technically correct, this view predictably appeared confusing.
In a similar manner it could be noted that, for example, the possible usefulness and validity of FLCCC’s protocols was unrelated to FLCCC members’ extra-medical opinions, and that ivermectin was only one component of the synergistic protocols consisting of more than ten components. Also, some news reports severely misrepresented the sepsis protocol . With regard to the social media communications of the FLCCC, it may have made a mistake in leaving these communications largely to a couple of ex-journalists whose communication style appeared unsuitable already in the ﬁrst half of 2020.
With regard to conﬂicts of interest, the members of US National Institutes of Health’s (NIH) ivermectinworking group had disclosed several relationships to pharmaceutical companies working on COVID-19 treatments . As mentioned, three of the nine members of the working group  had disclosed relationshipswith Merck & Co/MSD which, during the pandemic, had issued a statement against the use of ivermectinin COVID-19 , was working on a competing product molnupiravir [387,388,389], and had receivedsigniﬁcant US government funding for development of investigational pharmaceuticals for COVID-19 .
Adimora had received research support from Gilead Sciences and was a consultant and a member of an advisory board of Merck & Co/MSD; Bedimo was a member of advisory boards of Gilead Sciences, Merck &Co/MSD and ViiV Healthcare (a subsidiary of GlaxoSmithKline); Glidden was a consultant to Gilead Sciences and a member of an advisory board of Merck & Co/MSD . A fourth member, Pavia, was a consultant to GlaxoSmithKline. A ﬁfth member, Naggie, the head of US NIH’s ACTIV-6 trial (NCT04885530) had received research support from AbbVie and Gilead Sciences, had a connection to Bristol Myers SquibbCompany, and was a stockholder and an advisory board member of Vir Biotechnology, the producer ofsotrovimab together with GlaxoSmithKline . In summary, more than half of the members of the working group were associated with producers of molnupiravir, sotrovimab, remdesivir (Gilead Sciences),lopinavir/ritonavir (AbbVie), and investigational monoclonal antibodies (Bristol Myers Squibb Company).
However, NIH had speciﬁcally intended to involve the industry in its decision-making processes through the ACTIV public-private partnership . Whereas this organizational structure likely appeared beneﬁcialfrom the point of view of a swift development of investigational pharmaceuticals, with regard to repurposingit appeared to have included conﬂicts of interest by design.
For the pharmaceutical industry, incentives for unethical behavior may currently overpower those for ethical behavior. The current setting appeared designed for gambling , hardly the best method for optimizing public health, and it was diﬃcult to see why societies considered it appropriate.
The event descriptions did not delve into details of the experiences of Honduras and the Dominican Republic; readers are encouraged to acquaintance themselves with the original sources [217,106,107,311,312].
These countries used relatively little clinical trial evidence to implement their protocols. Similarly, no RCT evidence on FLCCC protocols exists, yet they have been successfully used. These parties seemed to embrace uncertainty instead of requiring an unattainable level of certainty; high-income countries were probably less accustomed to radical uncertainty than developing countries.
Cameron described critical care archetypes on a two-axis model, with the ﬁrst axis comparing interventionism(early, aggressive treatment) versus minimalism (’wait and see’) preferences, and the second axis measuring individualism versus collectivism . In this model, the FLCCC appeared high on interventionism and individualism. The ’mainstream’, for example the World Health Organization and national authorities, appeared high on minimalism and collectivism.
During the whole pandemic (and before it), little to no attention was paid to the optimization of innate immunity. If the immune system is dysfunctional or in a suboptimal state, attempts at medicating symptoms including symptoms of SARS-CoV-2 infection are unlikely to be very eﬀective, and the same likely applies to vaccines. While the role of zinc was acknowledged to some degree, the roles of, for example, copper, selenium and iodine were still mostly ignored. Conventionally, a long-term zinc supplementation without simultaneous copper supplementation is considered a risk for development of copper deﬁciency which would compromise immune function and host defence ; FLCCC recently lowered the dose of zinc supplementation. Astudy on European populations found a positive correlation between zinc suﬃciency status and COVID-19mortality and incidence, contrary to what would be expected if zinc suﬃciency was protective in COVID-19; however, the result might also indicate lack of zinc ionophores.
In addition to the methodological issues there were other types of challenges to overcome. Considering that the nature of communication between parties involved in the ivermectin controversy was predominantly ofa rather violent nature, a method for improving communications would be needed. A suitable method forthe purpose may be the rather well known but rarely applied ’non-violent communication’ (NVC) method developed by Marshall Rosenberg [395,396]. The method presupposes a willingness to a certain degree ofvulnerability in order to express one’s real needs and feelings, and a willingness to actually listen to others without judging.
The method consists of two parts: expressing oneself, and empathically acknowledging others. NVC deﬁnes empathy as ’a process of connecting with another by guessing their feelings and needs’ . Friesem describes the expressing part as a sequence of four steps: making observations (not evaluations) without blaming or criticizing, connecting feelings (bodily sensations instead of thoughts) to these observations, expressing the needs/values (not preferences) that caused the feelings, and making requests (concrete actions instead of vague wishes) without demanding . The listening part consists of the same steps but the expressions use the pronoun ’you’ instead of ’I’. The four components are thus expressed as ’when I/you see/hear. . . ’(observation), ’I/you feel. . . ’ (feeling), ’. . . because I/you need/value. . . ’ (need), and ’would you be willing to/would you like. . . ’ (request).
The content must be as free from interpretations as possible, instead expressed in a neutral ’observation anguage’. Feelings, which are functions of the states of satisfaction of various needs, must be identiﬁed, named, connected with, and expressed without interpretation. Needs must be distinguished from strategies(strategies include objects and parameters while needs do not). Requests are aimed at assessing how likelyone is to get cooperation for particular strategies for meeting one’s needs; requests should be concrete and speciﬁc. Pandemic-speciﬁc examples are left as an exercise for the reader. With regard to therapeutics research, it might be worth a try to organize a conference whose participants would be required to ﬁnd at least one detail they could agree on and then build on that foundation.
Considering that the communications at times appeared hopelessly dysfunctional, more potent methods are likely also needed. To a large extent, the damage associated with the pandemic was not caused by the virus itself but by a preexisting societal conditioning to ﬁxed beliefs and subconscious biases which eventually led to disorganized and dissociative behavior. This ’inﬂexible disorganization’ subsequently created a massive amount of additional anxiety, burnout and depression.
Psychedelic therapy, currently maybe the second most trendy research subject after COVID-19 itself, wouldlend itself well for resolving these issues [399,400,401,402,403,404]. Psychedelics are likely the most eﬀectivefacilitator of inspection of subconscious biases and ﬁxed beliefs, and as such a valuable tool especially forscientists. Smaller doses may be preferable; this practice is called psycholytic therapy. It diﬀers from the so-called ’microdosing’ in that doses are typically approximately a half or a third of a regular dose, and the eﬀects of the substance are clearly perceived but diﬀerent from those of high-dose psychedelic therapy.
Subconscious biases could be said to be a type of dissociative phenomena, in which a trigger related to a previous experience of overwhelming trauma triggers a slight dissociation, or a ’defence mechanism’. The mechanism of action of psychedelics in this case, in short, is to enable a person to relive the traumatic experience in order to neutralize the trigger. This must be done in an environment which provides thenecessary support so that the experience would not be experienced as overwhelming once again, as that would constitute a retraumatizing experience. Although various psychedelics produce slightly diﬀerent eﬀects, all of them would be useful for this kind of work. This includes also substances not always considered psychedelics,namely MDMA which is often called an ’empathogen’, and ketamine, often called a ’dissociative’.
Thus, an available pharmacological method would be oﬀ-label ketamine [405,406,407]. A trial by Federet al. compared treatment of post-traumatic stress disorder with either midazolam or ketamine (n=30)(NCT02397889) [408,409,410]. The mean score on the clinician-administered PTSD Scale for DSM-5(CAPS-5) was reduced from 40.1 to 33.2 in the midazolam group, and from 41.9 to 22.5 in the ketaminegroup. A similar reduction was observed for depressive symptoms.
A recent example of conﬂict resolution through altered states of consciousness, with promising results, was an attempt to alleviate the Israeli-Palestinian conﬂict by organizing ayahuasca group ceremonies .
The essence of psychedelic therapy, however, are not the molecules but the ’states of consciousness’, or states of mind, or emotional states, reached with the help of the molecules; change, progress or ’healing’ happens in or through these states. The same states may also be reached by other methods, although psychedelics provide a shortcut in situations in which there is a lack of time, skill or resources; the cost-eﬀectiveness of psychedelic therapy is typically superior to other methods.
Non-pharmaceutical methods capable of inducing altered states include holotropic breathwork developed by Stanislav and Christina Grof . Holotropic breathwork consists of continuous forceful circular breathing,combined with some bodywork and other techniques for guidance. The breathing technique leads to changes in oxygenation and typically to altered states of consciousness with the potential of resolving embodied traumatic experiences or opening new perspectives to overcome ﬁxed beliefs. Grof developed the method as an alternative to LSD therapy sessions and has described the states and results as similar. A gentler approach from Buddhist traditions, also applicable to trauma therapy, is the Ch¨od method based on visualization[413,414].
The Wim Hof method is applicable for innate immune system enhancement . In 2014, Kox et al.proved that sympathetic nervous system and immune system can be voluntarily inﬂuenced, and that itis possible to attenuate the innate immune response in humans [416,417]. Healthy volunteers practicing speciﬁc breathwork (hyperventilation), meditation and cold exposure techniques exhibited profound increases in the release of epinephrine, which in turn led to increased production of anti-inﬂammatory mediators and subsequent dampening of the proinﬂammatory cytokine response elicited by intravenous administration ofbacterial endotoxin. The Wim Hof method has numerous advantages: it is free, available to everyone,unlikely to produce adverse eﬀects, and unconnected to health care systems and clinicians.
Similarly to SARS-CoV-2 virus emerging as a possibly inexhaustible source of ever more infectious variants,the issue of COVID-19 treatments emerged as a possibly inexhaustible source of increasingly complex epistemological challenges. Current best practices of clinical trial result meta-analysis were found to be unsound;methodological changes were proposed. More broadly, the whole approach based on sole reliance on single agent clinical trials that no-one really wanted to fund appeared fundamentally unsound. The pandemic also revealed various severe problems with mindsets and subconscious biases; methods to overcome these issues were also proposed. The impression of the ivermectin controversy as a whole was that what is ideally understood by science will remain out of reach if scientists are riddled with subconscious biases, methodologies are fundamentally unsound, commercial interests dominate, and the behavior more closely resembles tribal warfare than a silent meditation retreat.
The author was responsible for all aspects of the manuscript.
This research did not receive any speciﬁc grant from funding agencies in the public, commercial, or not-for-proﬁt sectors.
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The author declares that he has no competing interests.
Independent researcher, Helsinki, Finland. ORCID iD: 0000-0002-8575-9838
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