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Greg Tucker-Kellogg publishes fraudulent study to attack ivermectin

Redação MPV
Aug 2023  
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Discussion of errors in This paper is highly flawed. For example, authors claim that there were "499 reported deaths - a citywide post-hospitalisation COVID death rate of 30.1% during the study period", which is not possible based on official data, (B). Authors appear to have used a mismatched dataset, incorrectly including data from neighboring municipalities (C), (D). Author's R code appears to incorrectly select patients (E). Authors also do not appear to have read the original paper in full, missing details of the population analyzed (F). They also appear to have missed the distinction between an individual's residential city and the location of their medical care (C), (G).
While it is possible these were accidental errors, two factors increase the severity.
The extreme mismatch in deaths with the original paper should have been a sign to check. The cause of the mismatch should have been relatively easy to determine, and in case authors were still stuck, they could have asked the original authors.
Such an extreme and easily identifiable error in mortality numbers undermines author's credibility.
Further, authors were notified of the mortality error within 12 hours of announcing the preprint on Twitter and acknowledged the error, initially claiming a rapid correction would be forthcoming. However, the paper has still not been corrected or withdrawn as of Sep 17, over a month after publication, and is still available without any warning or note. Leaving known highly incorrect information without correction for so long raises ethical concerns.
Discussion in this paper is highly biased, supporting concern over bias from the team. Authors claim that "rigorous randomised clinical trials have largely not found clinical benefit for ivermectin use in COVID-19", but cherry-pick low quality trials, and provide a highly misleading summary. First, in a paper analyzing prophylaxis, authors cite zero of the 16 other prophylaxis studies, including zero of the 4 prophylaxis RCTs. All of these RCTs report statistically significant positive results, contradicting the authors claim that "[RCTs] have largely not found clinical benefit".
Authors cite only 4 of the 99 studies, all with major issues, and none reporting prophylaxis results. Further, the 4 studies cited all show signs of efficacy - Lim shows 69% lower mortality, close to statistical significance; Bramante showed 61% lower hospitalization for ivermectin vs. placebo (not reported by authors, without statistical significance); the co-principal investigator of Reis has stated "there is a clear signal that IVM works in COVID patients"; and in Naggie the posterior probability ivermectin was effective was 99%, 98%, 97% for mean time unwell and clinical progression @14 and 7 days, all exceeding the pre-specified threshold for superiority (clinical progression results were changed without explanation between the preprint and journal version, the primary outcome was not reported, with a new post-hoc highly biased outcome created).
All 4 of the cited studies have major issues. For example, one trial reports impossible data, refuses to release data despite pledging to, and had randomization failure, blinding failure, and numerous protocol violations Reis.
Author's summary is discordant with reality - 60 studies show statistically significant positive results for one or more outcomes (including 23 RCTs) Abbas, Ahmed, Ahsan, Alam, Aref, Aref (B), Babalola, Behera, Behera (B), Bernigaud, Biber, Borody, Budhiraja, Bukhari, Cadegiani, Carvallo, Carvallo (B), Chaccour, Chahla, Chahla (B), Chowdhury, de Jesús Ascencio-Montiel, de la Rocha, Desort-Henin, Efimenko, Elalfy, Espitia-Hernandez, Faisal, Ghauri, Gorial, Hashim, Hellwig, IVERCOR PREP, Kerr, Khan, Lim, Lima-Morales, Mahmud, Mayer, Merino, Mondal, Morgenstern, Mourya, Naggie, Okumuş, Osati, Ozer, Qadeer, Rajter, Rezai, Rezk, Samajdar, Seet, Shahbaznejad, Shimizu, Shouman, Soto-Becerra, Spoorthi, Tanioka, Thairu.
Further, author's discussion of preclinical data is highly cherry-picked and highly misleading, with inaccurate interpretation of the concentration required based on Caly (see discussion) and other studies, and no mention of the majority of proposed mechanisms and supporting data.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CLpro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Redação MPV et al., 17 Aug 2023, preprint, 1 author.
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