Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID‐19
Hatem Elalfy, Tarek Besheer, Ahmed El‐mesery, Abdel‐hady El‐gilany, Mahmoud Abdel‐aziz Soliman, Ahmed Alhawarey, Mohamed Alegezy, Tamer Elhadidy, Asem A Hewidy, Hossam Zaghloul, Mustafa Ahmed Mohamed Neamatallah, Douaa Raafat, Wafaa M El‐emshaty, Nermin Y Abo El Kheir, Mahmoud El‐bendary
Journal of Medical Virology, doi:10.1002/jmv.26880
This trial compared the rate and time of viral clearance in subjects receiving a combination of nitazoxanide, ribavirin, and ivermectin plus Zinc versus those receiving supportive treatment. This non-randomized controlled trial included 62 patients on the triple combination treatment versus 51 age-and sex-matched patients on routine supportive treatment. all of them confirmed cases by positive reverse-transcription polymerase chain reaction of a nasopharyngeal swab. Trial results showed that the clearance rates were 0% and 58.1% on the 7th day and 13.7% and 73.1% on the 15th day in the supportive treatment and combined antiviral groups, respectively. The cumulative clearance rates on the 15th day are 13.7% and 88.7% in the supportive treatment and combined antiviral groups, respectively. This trial concluded by stating that the combined use of nitazoxanide, ribavirin, and ivermectin plus zinc supplement effectively cleared the SARS-COV2 from the nasopharynx in a shorter time than symptomatic therapy.
lower than effective in vitro concentrations against SARS-CoV-2. 43 A recent phase III clinical trial in dengue patients (DNV) in Thailand revealed that lower doses of ivermectin can be effective. A oncedaily dose of 400 µg/kg for 3 days was found to be safe but did not produce any clinical benefit, and showed a modest and indirect in vivo effect against DNV. 44 The antioxidant, anti-inflammatory, immunomodulatory and antiviral activities of Zn are well known. Its antiviral effect is mediated by suppressing RNA-dependent RNA polymerase (RdRp). 45 Zinc ions (Zn 2+ ) are closely involved in the normal development, differentiation, and function of immune cells, thus considered critical for generating both innate and acquired (humoral) antiviral responses. 32 The synergistic effect of zinc, if combined with antiviral treatment, has been proved previously with hepatitis C virus, human papillomavirus, viral diarrhea in children, and human immunodeficiency virus. 46-49 Short-term treatment with zinc in therapeutic doses is completely safe. Zn toxicity rarely occurs in very sporadic cases unlike many other metal ions with similar chemical properties. 50 Study limitation: the groups were not randomized and the drug combination does not have an established in vitro mechanism of action and remains exploratory.
| CONCLUSION The results of this study confirm that combined use of nitazoxanide, ribavirin, and ivermectin plus zinc supplement effectively cleared the SARS-COV2 from..
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