THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19: A SYSTEMATIC REVIEW OF MECHANISMS AND EVIDENCE (preprint)

Introduction: Ivermectin is a commonly used antihelminthic agent with over 35 years of established safety data in humans. Recent data demonstrates antiviral activity in vitro against SARS-CoV-2, in addition to a range of viruses. In vitro and animal models also provide evidence of immunomodulatory action. These additional modes of action are supported by in silico modelling, which propose a number of viral and host targets that would mediate these effects. Objectives: The aim of this study is to systematically review the published and preprint clinical literature and study results that assessed the potential role of ivermectin as a COVID-19 therapeutic and prophylactic agent. Methods: We conducted a comprehensive review of PubMed, medRxiv, ClinicalTrials.gov, Global Coronavirus COVID-19 Clinical Trial Tracker, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, ANZ clinical trials registry, and references from relevant articles. PRISMA guidelines for systematic reviews were employed. Results: Search keywords- “COVID-19 (and synonyms) AND ivermectin”- generated 86 articles on PubMed, 48 on medRvix and 37 on clinicaltrials.gov at the time of writing. Twelve of these were listed as completed clinical trials and of these, 8 were included as investigators had released results. Positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression and decreased duration of hospital admission were reported in patients across all stages of clinical severity. Limitations: Due to the time-critical nature of the COVID-19 pandemic our review included preprint data, which must be interpreted with caution while it awaits peer review.

Nanocell COVID-19 vaccine elicits iNKT-licensed dendritic cells to produce high affinity antibodies neutralizing Variants of Concern (preprint)

For COVID-19 vaccines, high-affinity antigen-specific antibody, CD8+ T cell and memory B cell responses are essential to maximize protection against Variants of Concern (VOC). We report results in vitro, in mice and human volunteers immunized with bacterially-derived, non-living nanocells (EDVTM) packaged with bacterial plasmid expressing spike protein of SARS-CoV-2 and IFNγ stimulating adjuvant α-galactosylceramide (EDV-COVID-αGC). EDV-COVID-αGC is shown to elicit iNKT-licensed dendritic cell activation/maturation, follicular helper T cell cognate help to B cells to undergo germinal center based somatic hypermutation and production of high affinity antibodies able to neutralize Alpha, Beta, Gamma, Delta, and Omicron VOC including a memory B cell response. Type I and Type II interferon stimulation and S-specific CD8+ T cells was also achieved. EDV-COVID-αGC are lyophilized, stored and transported at room temperature.

THE THERAPEUTIC POTENTIAL OF IVERMECTIN FOR COVID-19: A REVIEW OF MECHANISMS AND EVIDENCE (preprint)

IntroductionIvermectin is a commonly used antihelminthic agent with over 35 years of established safety data in humans. Recent data demonstrates antiviral activity in vitro against SARS-CoV-2, in addition to a range of viruses. In vitro and animal models also provide evidence of immunomodulatory action. These additional modes of action are supported by in silico modelling, which propose a number of viral and host targets that would mediate these effects. ObjectivesThe aim of this study is to systematically review the published and preprint clinical literature and study results that assessed the potential role of ivermectin as a COVID-19 therapeutic and prophylactic agent. MethodsWe conducted a comprehensive review of PubMed, medRxiv, ClinicalTrials.gov, Global Coronavirus COVID-19 Clinical Trial Tracker, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, ANZ clinical trials registry, and references from relevant articles. ResultsSearch keywords- "COVID-19 (and synonyms) AND ivermectin"- generated 86 articles on PubMed, 48 on medRvix and 37 on clinicaltrials.gov at the time of writing. Twelve of these were listed as completed clinical trials and of these, 8 were included as investigators had released results. Positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression and decreased duration of hospital admission were reported in patients across all stages of clinical severity. LimitationsDue to the time-critical nature of the COVID-19 pandemic our review included preprint data, which must be interpreted with caution while it awaits peer review.