Use of Ivermectin for the Treatment of COVID-19 (updated January 14, 2021)
Ivermectin is an antiparasitic drug that is approved by the Food and Drug Administration (FDA) for the treatment of onchocerciasis (disease is spread by repeated bites from infected black flies),
and strongyloidiasis (infection by a roundworm). This drug is commonly used in veterinarian medicine. In general, this is a drug well tolerated.
Ivermectin is not FDA-approved for the treatment of any viral infection.
Recently numerous, inconclusive studies have looked at Ivermectin for use in treatment of COVID-19. While the in vitro(test tube) studies indicated potential benefit, human use brought differing results. Some studies showed no benefits while others indicated possible shorting of symptoms. However, most of the studies conducted reported incomplete data and significant methodological limitations. Here are some of the red flags raised from these studies:
1). Sample size of the trials were small. This is a problem in it does not represent the scope of ages, genders, health status equally to draw conclusions.
2). A variety of doses and schedules of the drug was used. This makes comparison impaired—the proverbial comparing apples to oranges approach.
3). Some of the trails were not blinded. The gold standard for clinical trials is blinded so data cannot be manipulated.
4). Ivermectin was not the only drug used on the patient. Patients also received doxycycline, hydroxychloroquine, azithromycin, zinc, and/or corticosteroids. Raising the question as to which drug(s) made the difference.
5). Many times the severity of the COVID-19 patient was not well documented. You cannot mix severe and mild cases without specifying how it worked in each situation.
6). Finally, the outcome measures for the studies were not well defined. Studies must have defined outcome parameters to know whether positive or negative results occur.
7). The Panel (COVID-19 Treatment Guidelines Panel) has determined it is not possible to make definitive conclusion statement about the clinical safety or efficiency of ivermectin for treatment of COVID-19.
Of Most Importance
It should be noted the in vitro studies (test tube) required 100 times higher than the approved for human use dosage to bring about an effect. This brings further concern to the safety and effectiveness of this drug.
Dianna Richardson, ND January 15, 2021
References:
National Institute for Heath (2021). The COVID-19 Treatment Guidelines Panel on the Use of Iverrmectin for the treatment of COVID-19. https://www.covid19treatmentguidelines.nih.gov/statement-on-ivermectin/
Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer. Antiviral Res. 2020;177:104760. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32135219.
Arévalo AP, Pagotto R, Pórfido J, et al. Ivermectin reduces coronavirus infection in vivo: a mouse experimental model. bioRxiv. 2020;Preprint. Available at: https://www.biorxiv.org/content/10.1101/2020.11.02.363242v1.
Lehrer S, Rheinstein PH. Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2. In Vivo. 2020;34(5):3023-3026. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32871846.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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/.
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.
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.
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.
Understanding the Silent Hypoxemia of COVID-19
What is silent hypoxemia? It is a condition that occurs when oxygen levels in the body are abnormally low, which can irreparably damage vital organs if gone undetected for too long.
Many people inflicted with severe cases of COVID-19 sometimes show no symptoms of shortness of breath or difficulty breathing. However, they are experiencing dangerously low levels of oxygen. Hypoxia has the ability to quietly inflect damage; thus, the term silent hypoxia.
Research and computer models has revealed the coronavirus may inflict damage to the lungs resulting in the inability to function properly.
Lung tissues lose oxygen and stop working, no longer infusing the blood stream with oxygen, causing silent hypoxia.
Some coronavirus patients have experienced what some experts have described as levels of blood oxygen that are "incompatible with life." Yet, the lung scans of many of these patients showed little to no signs of abnormality. How is this possible?
Research, published in Nature Communications, has revealed a three-fold path to silent hypoxia in COVID-19 patients. A group of biomedical engineers used computer modeling to test out three different scenarios that help explain how and why the lungs stop providing oxygen to the bloodstream.
Our lungs serve to exchanges gases. We breathe in oxygen and exhale carbon dioxide. Healthy lungs perform this gas exchange at a rate keeping essential oxygen levels at cellular level between 95-100%. If your oxygen rates drop below 92% there is concern as vital organs maybe begin stressing due to reduced saturation.
So, what is different with coronavirus infection? In a normal situation, infections in the lungs will trigger a constricting of blood vessels to any damaged areas. This is important as the blood flow is then redirected to healthy lung tissue so body levels of oxygen can be maintained. Research has shown this process dysfunctions in severe COVID-19 patients. Instead of restricting blood flow in infected (poorly functioning) areas of lung tissue, the opposite is happening. Blood vessels in damaged areas are opening to a greater degree (not easy to see or measure on CT scans). This contributes to lower oxygen levels throughout the body.
The second fold in silent hypoxia involves blood clotting. The inflammatory response of COVID-19 allows tiny blood clots, too small to be seen on medical scans, to potentially form inside the vessels of the lungs. While it is not believed this alone would cause silent hypoxia, impairment of oxygen flow would exist.
Finally, using their computer model, researchers found the normal ratio of air-to-blood flow could be impaired. Mismatched air-to-blood flow occurs in many respiratory illnesses, including asthma. Again, this would be happening in the impaired parts of the lungs—contributing to silent hypoxia. This is difficult to identify as scans do not reveal this type of injured or abnormal lung condition.
These findings show the combined actions happening within the luligs result in silent hypoxia. Presence of all three are likely responsible for the severe cases of COVID-19. It also explains why prone-positioning (flipping patients on stomach vs. back) has been beneficial in many patients. This allows for the back part of the lungs to pull in more oxygen and evening out the mismatched air-to-blood ratio. Thereby removing one portion of the three-fold equation.
Bottom line…
Knowing the factors contributing to silent hypoxia allows for better treatment options. Attending clinicians now know addressing potential blood clots, creating vessel constrictions, and balancing mismatched air-to-blood flow ratio are all vital to successful treatments.
Dianna Richardson, ND January 2021
Reference:
Jacob Herrmann, Vitor Mori, Jason H. T. Bates, Béla Suki. Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia. Nature Communications, 2020; 11 (1)