Changes in SpO2 on Room Air for 34 Severe COVID-19 Patients after Ivermectin-Based Combination Treatment: 62% Normalization within 24 Hours

Stone, Jaqueline C.; Ndarukwa, Pisirai; Scheim, David; Dancis, B.M.; Dancis, Jerome; Gill, Martin G.; Aldous, Colleen

doi:10.3390/biologics2030015

Cited by 9 publications

(15 citation statements)

References 44 publications

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“…IVM at concentrations of 1–2 µM for the four different viral lineages inhibited HA when added concurrently with spike protein and also reversed HA that had been induced by the prior addition of spike protein. This HA-reversal effect could account for sharp increases observed within 24 h after administration of IVM of pre-treatment depressed SpO2 levels in severe COVID-19 patients, as summarized in Figure 6 below, which reproduces a figure from the most recent of three clinical studies reporting this effect [ 64 ]. In contrast to the sharp, rapid increases in SpO2 levels observed in these studies, moderate and severe COVID-19 patients under standard care typically manifest decreasing SpO2 values in tandem with increasing pulmonary CT abnormalities from the day of onset of disease symptoms through the second week following, as established in several studies that tracked SpO2 values, pulmonary abnormalities, or both [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Section: Discussionsupporting

confidence: 54%

“… Mean changes in oxygen saturation (SpO2) for severe COVID-19 patients following treatments including or excluding IVM. Reproduced from Stone et al, 2022 [ 64 ] (CC-BY 4.0). Patients tracked over various time periods from each regimen were those with SpO2 values all recorded on room air, having pre-treatment (day 0) values ≤ 93%.…”

Section: Discussionmentioning

confidence: 99%

“… ● Hazan et al, 2021 [ 86 ]: 19 patients, median age 63, treated with IVM, doxycycline and zinc. ● Stone et al, 2022 [ 64 ]: 34 patients, median age 56.5, treated with IVM, doxycycline and zinc.…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Boschi

Scheim²,

Bancod

et al. 2022

IJMS

Self Cite

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Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterward. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines, which use spike protein as the generated antigen.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Boschi

Scheim²,

Bancod

et al. 2022

IJMS

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“…Also, increase in SPO2 on IVM was magnified in Males (Figure 5). Similar findings of rapid rise in SPO2 on Ivermectin was reported by Stone et al 40 . In 34 patients treated in Zimbabwe, the authors noted a mean increase in SpO2 as a percentage of full normalization to SpO2 = 97% of 55.1% at +12 h and 62.3% at +24 h after the first IVM dose (pairedt-test,p< 0.0000001).…”

Section: Ivermectin and Changes In Arterial Oxygensupporting

confidence: 90%

The Place of Ivermectin in the Management of Covid-19: State of the Evidence

O.E

Adesuyi

2023

MRAJ

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Background and aims. The covid 19 pandemic necessitated the use of old, repurposed, and new drugs, in addition to vaccines and public health measures. There are still many controversies about the efficacy and impact of some of the medications used, which need further elucidation. We review the pharmacological properties and the place of the repurposed drug, Ivermectin (IVM) in the prophylaxis and treatment of SARS - CoV- 2 (severe acute respiratory syndrome coronavirus 2.) infection or Covid 19 disease. Major findings: in-vitro, in-vivo, and human studies In vitro studies in Vero/hSlam cells caused a 99.98 % inhibition of SARS - Cov-2 (5000-fold) within 48 hours. The IC50 (half maximal inhibitory concentration) for this virucidal action was 2.8μM, which was thought unattainable in humans in-vivo. Thus, there was initial skepticism on pharmacokinetic grounds as to possible efficacy of IVM in humans with Covid 19. There are, however, a multiplicity of anti-covid 19 mechanisms, beyond mere anti-viral effects, such as blockade of ACE2 receptor viral entry, and the anti-cytokine and anti-inflammatory effects of IVM. IVM has a long half-life of 18 - 24 hours, Mean Residence Time (MRT) of 3.4 days and a preferential site of lung accumulation. In-vivo studies in Syrian Golden hamsters confirmed the symptomatic, anti-inflammatory, anti-cytokine, histopathological and survival benefit of IVM, which was more manifest in female animals. In a January 2023 meta-analysis of studies (s) in total number of patients (n) for various parameters (p), the reduction in risk relative to placebo or controls were as follows: Overall improvement (s= 95) (n= 134,554) was 62% [95%CI 54-69]. Mortality (s=48) (n=120,000) there was 51% reduction [95%CI 37-62]. Hospitalization (s=29) (n = 44, 784), there was 34% reduction [ 95% CI 20-45]. Viral clearance (s=20) (n= 3945) there was 45% reduction [95%CI 31-55]. Prophylaxis (s=17) (n=19,764) showed 82% reduction [95%CI 73-88] 6 Randomised Control Trial (RCT) studies (s= 45) (n=2173) showed a 54 % mortality reduction [95% CI 39-65] In addition, IVM has been shown in studies to cause a rapid reversal of hypoxemia (SPO2 < 94%) and a rapid increase in SPO2, an effect exhibiting a gender dichotomy. (SPO2 is the percentage of the maximum carrying capacity of the blood). This effect on SPO2 has been attributed to IVM’s reversal and prevention of SARS-CoV-2 virus induced hemagglutination. The dosage used for treatment of covid 19 varied widely within studies, but doses of 200-400 μg/kg twice weekly or daily for 5 consecutive days, caused significant viral clearance and clinical improvement, with minimal safety concerns. For prophylaxis, a dose of 200μg/kg for two consecutive days every 15 days was found effective in studies. Conclusion: This review provides powerful evidence that IVM is efficacious singly or as a part of a regimen for covid 19. IVM could potentially be combined with newer oral anti-covid 19 agents, such as Paxlovid, for effective and life-saving regimen in patients infected with covid-19. The anti-viral properties of these drugs can synergize with the anti-inflammatory and anti-cytokine properties of Ivermectin. Ivermectin is also useful prophylactically, especially where vaccines are unavailable or undesirable.

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“…This HA-reversal effect could account for sharp increases observed within 24 hours after administration of IVM of pre-treatment depressed SpO2 levels in severe COVID-19 patients, as summarized in Figure 6 from the most recent of three clinical studies reporting this effect. 62 The inhibition of HA by IVM as reported here parallels the prevention of RBC clumping in Zebrafish embryos by heparan sulfate, a glycosaminoglycan likewise indicated to strongly bind to SARS-CoV-2 spike protein, 49,63 when coinjected with spike protein. 49 It is noteworthy that the scattered RBC clumps observed in this Zebrafish embryo study, as with those observed in the blood of COVID-19 patients, 26-28 are much smaller than the macroscopic-scale HA—clusters of extensively interlaced RBCs—observed in this study.…”

Section: Discussionsupporting

confidence: 65%

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Boschi

Scheim

Bancod

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than for the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterwards. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines which use spike protein as the generated antigen.

show abstract

Changes in SpO2 on Room Air for 34 Severe COVID-19 Patients after Ivermectin-Based Combination Treatment: 62% Normalization within 24 Hours

Cited by 9 publications

References 44 publications

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

The Place of Ivermectin in the Management of Covid-19: State of the Evidence

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

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