Let Us Take a Closer Look at Ivermectin!

Let Us Take a Closer Look at Ivermectin!

by Adel Eldin, MD FACC FACP, MBA, GGA

As we approach a record death toll of 400,000 fellow Americans, millions infected with COVID-19, it is a sober reminder that there is a desperate need to seek a durable effective therapy beyond vaccination. Ivermectin is an anti-parasitic medication that has been used globally over the past 40 years with an established safety profile. The Global Pandemic has shown without a double that effective and safe therapy for Coronavirus is desperately needed globally. Obviously, having a vaccine out is a good thing but the need for a therapy that prevents and treats those infected with coronavirus is tremendously important.

There is some encouraging data from randomized clinical trials and observational data showing Ivermectin-treated patients had a shorter hospital stay, faster viral clearance, faster clinical recovery, and a significant reduction in mortality rates.

Ivermectin has a strong anti-inflammatory effect, prevent transmission of COVID-19 when taken before or after exposure to Coronavirus, inhibit replication of many viruses, and help earlier recovery from COVID-19.

There are three clear mechanisms of Coronavirus damage to the lungs causing a decrease in the Oxygen Saturation level which is treated with supplemental Oxygen, the second mechanism is the development of many small blood clots that interferes with Oxygen exchange and that is treated with blood thinners. The third mechanism is a very super inflammatory response called ( cytokine storm) which can lead to lung damage and again reduces Oxygen saturation and that is treated by Intravenous Dexamethasone( IV Steroid therapy).

Coronavirus infection has both airborne( aerosol) and droplet spread, replicating in the throat ( pharynx in the upper respiratory tract ), then travels down to the lungs ( lower respiratory tract) causing pneumonia. That is why it is so important when feeling sore throat, it is important to gargle with either water and salt or apple cider vinegar and water to prevent complicating pneumonia.

It must be noted that viral load is the highest and thus infectivity is also highest before the onset of symptoms which makes wearing facemasks very important to protect both the person wearing it and the people who come in contact.

A summary of the current and proposed therapies for Coronavirus have shown No benefit or a tread to harm from Hydrocholoroquin, No mortality benefit from Remedisivr but, reduced time spent in the Intensive Care Unit ( reduced time to recovery).

Convalescent plasma showed No mortality benefit, Monoclonal antibodies (Tocilizumab) showed No benefit and can lead to late added bacterial infection because they contain IGg which is a big protein molecule that circulates in the blood can not get into the tissue to have a therapeutic effect. On the contrary, Ivermectin has a significant binding affinity with various proteins which may block viral entry and may help modulate the immune response to COVID-19 which can help in the early phase of infection. Ivermectin has an anti-inflammatory effect which can help in late-stage COVID-19 infection. Data from various countries including Argentina showing oral Ivermectin decreased COVID-19 infection. Also, a study from Egypt using Ivermectin for the prevention of COVID-19 compared with a group that did not get it while both groups had use PPEs ( Personal Protective Equipments).

Observational data of Ivermectin use in Beru, Brazil, and Africa using for those with parasitic infections were found to have less incidence of COVID-19 infection. There are other helpful therapies such as high dose Vitamin C used in cases of severe infections in addition to putting patients in the Prononig position. FDA has just made a statement regarding Ivermectin as regarding the available  information and limitations include the following:

• The sample size of most of the trials was small.
• Various doses and schedules of ivermectin were used.
• Some of the randomized controlled trials were open-label studies in which neither the participants nor the investigators were blinded to the treatment arms.
• In addition to ivermectin or the comparator drug, patients also received various concomitant medications (e.g., doxycycline, hydroxychloroquine, azithromycin, zinc, corticosteroids), confounding the assessment of the true efficacy or safety of ivermectin.
• The severity of COVID-19 in the study participants was not always well described.
• The study outcome measures were not always clearly defined.

Because of these limitations, the Panel cannot draw definitive conclusions about the clinical efficacy or safety of ivermectin for the treatment of COVID-19. Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19.

Perhaps, it is time to launch those randomized trials to take a closer look into Ivermectin and its many potential beneficial effects on the prevention and treatment of the Worldwide Pandemic caused by Coronavirus infection. Certainly, this worthwhile effort to save so many lives and avoid the preventable deaths of so many here at home and around the globe!

References

1. Guzzo CA, Furtek CI, Porras AG, et al. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002;42(10):1122-1133. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12362927.
2. Chaccour C, Hammann F, Ramon-Garcia S, Rabinovich NR. Ivermectin and COVID-19: keeping rigor in times of urgency. Am J Trop Med Hyg. 2020;102(6):1156-1157. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32314704.
3. Arshad U, Pertinez H, Box H, et al. Prioritization of anti-SARS-CoV-2 drug repurposing opportunities based on plasma and target site concentrations derived from their established human pharmacokinetics. Clin Pharmacol Ther. 2020;108(4):775-790. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32438446.
4. Bray M, Rayner C, Noel F, Jans D, Wagstaff K. Ivermectin and COVID-19: a report in antiviral research, widespread interest, an FDA warning, two letters to the editor and the authors’ responses. Antiviral Res. 2020;178:104805. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32330482.
5. Zhang X, Song Y, Ci X, et al. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflamm Res. 2008;57(11):524-529. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19109745.
6. Ci X, Li H, Yu Q, et al. Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. Fundam Clin Pharmacol. 2009;23(4):449-455. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19453757.
7. DiNicolantonio JJ, Barroso J, McCarty M. Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19. Open Heart. 2020;7(2). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32895293.
8. Ahmed S, Karim MM, Ross AG, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 2020;103:214-216. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33278625.
9. Chachar AZK, Khan KA, Asif M, Tanveer K, Khaqan A, Basri R. Effectiveness of ivermectin in SARS-COV-2/COVID-19 Patients. Int J of Sci. 2020;9:31-35. Available at: https://www.ijsciences.com/pub/article/2378.
10. Chowdhury ATMM, Shahbaz M, Karim MR, Islam J, Guo D, He S. A randomized trial of ivermectin-doxycycline and hydroxychloroquine-azithromycin therapy on COVID19 patients. Research Square. 2020;Preprint. Available at: https://assets.researchsquare.com/files/rs-38896/v1/3ee350c3-9d3f-4253-85f9-1f17f3af9551.pdf.
11. Soto-Becerra P, Culquichicón C, Hurtado-Roca Y, Araujo-Castillo RV. Real-world effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: results of a target trial emulation using observational data from a nationwide healthcare system in Peru. medRxiv. 2020;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v3.
12. Hashim HA, Maulood MF, Rasheed AW, Fatak DF, Kabah KK, Abdulamir AS. Controlled randomized clinical trial on using ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq. medRxiv. 2020;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2020.10.26.20219345v1/.
13. Elgazzar A, Hany B, Youssef SA, Hafez M, Moussa H, eltaweel A. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Research Square. 2020;Preprint. Available at: https://www.researchsquare.com/article/rs-100956/v2.
14. Niaee MS, Gheibi N, Namdar P, et al. Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: a randomized multi-center clinical trial. Research Square. 2020;Preprint. Available at: https://www.researchsquare.com/article/rs-109670/v1.
15. Khan MSI, Khan MSI, Debnath CR, et al. Ivermectin treatment may improve the prognosis of patients with COVID-19. Arch Bronconeumol. 2020;56(12):828-830. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33293006.