Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia Part II: Causal inference using the Bradford Hill criteria
Ph.D Eleftherios Gkioulekas, M.D Peter A Mccullough, Ph.D Colleen Aldous
doi:10.11553/antibiotics.78.1_35
We continue the critical appraisal of three published case series of 119 COVID-19 patients with hypoxemia, treated in the United States, Zimbabwe, and Nigeria with similar ivermectin-based multidrug treatments, to assess the available evidence supporting a causal relationship between treatment and reduction in hospitalizations and mortality. A narrative review was conducted to assess the Bradford Hill criteria for a causal association. We used a previously proposed refinement of the Bradford Hill criteria that reorganized them into three categories of direct, mechanistic, and parallel evidence. The efficacy of the two most aggressive ivermectin-based multidrug protocols is supported by the Bradford Hill criteria for temporality, strength of association, biological gradient, biological plausibility, coherence, consistency, and analogy. The causal relation between the treatment of hypoxemic COVID-19 patients using these protocols and the reduction in hospitalizations and mortality is supported as an inference to the best explanation.
Abbreviations ACE2, Angiotensin-Converting Enzyme 2; AgNP, silver nanoparticles; CFR, Case Fatality Rate; CD147/EMMPRIN, Cluster of differentiation 147 / extracellular matrix metalloproteinase inducer; COVID-19, Coronavirus Disease 2019; DPP4/CD26, Dipeptidyl peptidase 4 / cluster of differentiation 26; IL-6, Interleukin 6; IMP, importin; MERS, Middle Eastern Respiratory Syndrome; MMP-9, matrix metalloproteinase-9; NF-κB, Nuclear factor kappa B; RDRP, RNA Dependent RNA Polymerase; S1-NTD, S1-N-Terminal Domain; S1-RBD, S1 Receptor Binding Domain; PVP, poly (N-vinyl-2-pyrrolidone); ROS, Reactive Oxygen Species; RAS, Renin Angiotensis System; SARS, Sudden Acute Respiratory Syndrome; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; SpO 2 , Peripheral oxygen saturation; TNF-α, tumor necrosis factor alpha.
Ethics approval and consent to participate Not applicable. The study is an analysis of previously published data.
Conflict of interest Peter McCullough is the part-time Chief Scientific Officer for the Wellness Company, Boca Raton, Florida, United States of America, which had no role in the study or the writing of the manuscript. Eleftherios Gkioulekas is affiliated with the School of Mathematical and Statistical Sciences at The University of Texas Rio Grande Valley, which regularly invites visiting scholars from other academic institutions and directly receives donations to fund scholarships, however he has not himself hosted any visiting scholars or received a..
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DOI record:
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"DOI": "10.11553/antibiotics.78.1_35",
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"container-title": "The Japanese Journal of Antibiotics",
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"title": "Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia Part II: Causal inference using the Bradford Hill criteria",
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