Back in May 2020, TrialSite announced the study titled a pilot clinical trial led by Egypt’s Mansoura University, located in the middle of the Nile Delta region. A highly ranked academic medical research center within this Middle East nation, a team of investigators there led by two doctors and faculty of medicine professors, sought to test whether the combination of Nitazoxanide, Ribavirin, zinc and Ivermectin clears SARS-CoV-2, the virus behind COVID-19? With results now published in the peer reviewed Journal of Medical Virology, the team has an answer. Disclosed initially as both a randomized and sequential clinical trial (later declared non-randomized), the authors were able to enroll 62 in the combination, Ivermectin-based arm and 51 on the standard of care or “supportive therapy.” Those COVID-19 patients in the Ivermectin-based treatment group fared far better. By Day 7, while there was 0% clearance in the standard of care group, 58.1% of the combination Ivermectin-based group experienced viral clearance. By Day 15, 73.1% of the Ivermectin-based arm were fully cleared of SARS-CoV-2 while only 13.7% of those on the standard of care were cleared of the virus. The cumulative clearance rates by Day 15 were 88.7% and 13.7% for Ivermectin/combination and supportive treatment, respectively. The authors declared that based on the results, the combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement effectively clear COVID-19 from nasopharynx at significantly faster rate than those on the supportive therapy.
The results of this study were published in the monthly, peer-reviewed medical journal called Journal of Medical Virology. The Ivermectin dosages used in this study were repeated and higher than many of the other studies.
In addition to Ivermectin, the team introduced Nitazoxanide, an oral anti-parasitic drug showing activity against numerous protozoa and helminths. In recent studies, it’s suggested that the drug has a possible antiviral activity, as well as an immune modulatory effect suppressing the inflammatory cytokines such as IL-6 and TNF alpha 4-7. In vitro studies suggested that the drug may have activity against SARS-CoV-2 replication but there is little evidence as to effectiveness in a clinical environment. A randomized, placebo-controlled study in Brazil showed promise against COVID-19. A later study in Mexico also reaffirms the positive potential for use of Nitazoxanide.
While the guanosine analogue Ribavirin exhibits broad-spectrum antiviral impact against RNA and DNA viruses, the authors note that the mechanism of action association with ribavirin isn’t clear but could involve inhibition of mRNA capping and introduction of mutations during viral replication as well as indirect antiviral activity mediated via immune regulatory pathways is considered by some researchers.
Of course, the benefits of Ivermectin have become widely known although still shunned by a majority of the medical and journalistic establishment. While the drug is approved by the U.S. FDA and used in many countries as an antiparasitic medication, it has exhibited antibacterial and antiviral activity. Of course, the well known in vitro lab experiments at University of Monash, Australia, triggered over 50 formal clinical trials, most of which have show efficacy with no concerning safety signals.
The use of zinc is questionable. There is no evidence that zinc helps contribute to fighting COVID-19 while the U.S. FDA has sent warning letters to at least five different companies that advertised that a zinc-based product would help prevent or treat COVID-19. The World Health Organization posits more evidence is needed before any claims can be made. The U.S. National Institutes of Health also declares lack of sufficient evidence for the mineral supplement in regards to treating COVID-19.
On the other hand, the study authors share that zinc has well-known antioxidant, anti-inflammatory, immunomodulatory and antiviral activities—the latter involving the suppression of RNA-dependent RNA polymerase (RdRp).
The authors note that they were not able to ultimately execute on a randomized controlled trial, and critics will undoubtedly point this out. Moreover, the drug combination used was novel with no in vitro mechanism of action, purely an exploratory situation at this point.
Ivermectin: Accumulation of Data
Meta-analyses from researchers in both the United Kingdom and America reveal powerfully positive impact. A Panel of experts from the U.S. National institutes of Health COVID-19 Treatment Guidelines actually changed their position on the drug from recommending against, to only for research, to a neutral stance awaiting further study data.
A common critique embraced by the NIH and other research agencies is the quality associated with the underlying Ivermectin studies. While other researchers have declared that there is sufficient evidence, including those meta-analyses authors, such as Dr. Andrew Hill (University of Liverpool, Unitaid), Dr. Tess Lawrie, and in the United States, the Front Line COVID-19 Critical Care Alliance.
A group of anonymous but really bright scholars, researchers and scientists designed @CovidAnalysis, revealing compelling data in a nice, clean and orderly manner—the evidence for the drug used by hundreds of millions (billions of doses consumed) is compelling for those that choose to look carefully.
The Journal of Medical Virology focuses on primary and applied research centered on viruses affecting humans. Published by Wiley-Blackwell, this journal was established in 1977. The most recent editor-in-chief is Shou-Jiang Gao of the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center Virology Program. Wiley-Blackwell is actually the subsidiary of Wiley, an American multinational publishing company founded in 1807.
Hatem Elalfy, MD, Faculty of Medicine
Other authors can be viewed at the source here.