The COVID-19 Conundrum, Part II

The Delta variant is old news and we must brace ourselves for the more vaccine-resistant mu variant. As the COVID-19 story continues to mature, our knowledge about treatment strategies are also evolving.  If we critically examine the data from Israel, with almost 80% of their population vaccinated, we have to acknowledge that vaccine efficacy is demonstrably waning, especially against the new variants. Israel is not the only example of vaccine failure; Cornell University, has a 95% vaccination rate with increasing cases above baseline modeling. I anticipate that this trend will continue as we approach this virus with blinders, believing that universal vaccination is the ONLY way to beat it.  Our health departments (WHO, CDC and FDA) and pharmaceutical companies are doing a major disservice to 46% of the population by not investigating alternative therapeutic options and only advocating vaccination as the sole treatment option. There are currently enough vaccine doses available to fully vaccinate every American, but it turns out that not every American wants it. It is time that we start to consider ivermectin and hydroxychloroquine as viable substitutes to the vaccine-reluctant patients. With emerging clinical data suggesting reasonable efficacy of these two medications in the treatment of COVID-19, I find the AMA statement disgusting and lacking in curiosity.

The AMA statement addresses concern for risk of toxicity as the reason to avoid Ivermectin use. It should be recognized that Ivermectin has been used in humans for over 25 years with a well-documented safety profile. In the COVID-19 treatment protocols, it suggests 12mg/day for 5 days or 60mg total in 120 hours. When evaluating toxicity of a pharmaceuticals, they represent this information as LD50 (lethal dose of 50% of subjects). For Ivermectin, the LD50 is 10mg/kg.  Given the average physiologic human, reported in medical textbooks is 70kg, the median 50% lethal dose is 700mg (58x the therapeutic dose). The actual LD50 dosage is much higher because 70kg is a 154 pounds. Most people suffering from severe COVID are much larger than 150 pounds. With a half-life of 18-hours (excretion through feces, so kidney function plays no role in the pharmacokinetics) and a dosage of 12mg/day, this dosage is well below the toxic range. Current dosing schedules for parasitic infections is 0.2mg/kg.  Taking our same, arbitrary 70kg individual, the dosage suggested for treatment is 14mg/day. Recommending 12mg/day for 5 days clearly is within the safety and therapeutic threshold.

Some studies have suggested efficacy of ivermectin (here, here, video and here) for treatment of severe COVID-19 and hydroxycholorquine (here and here) might be a prophylactic agent or provide some symptom relief for mild cases. Either way, therapeutic options need to be investigated for people that are staunchly vaccine averse, cannot receive the vaccine for medical reasons or for those with breakthrough infections of new variant strains. Myopic treatment strategies and reliance on a single approach for an unstable viral genome is poor practice. Resistant strains of microorganisms is not uncommon. If an antibiotic or chemotherapeutic agent demonstrates poor response to an infection or neoplasm, respectively, we alter the treatment for a more appropriate, desired response.  A patient that receives the influenza vaccine, but then gets infected with the flu, doesn’t require an influenza booster, this is illogical thinking.

Dissent to vaccine mandates does not imply that this subpopulation is villainous, nor dangerous.  If someone chooses to get the vaccine, they can anticipate less aggressive symptoms from COVID-19 if infected, despite a 0.04% risk of severe COVID symptoms in the unvaccinated.  People who choose to remain unvaccinated have accepted the consequences of their choices and the 99.96% chance of being asymptomatic or getting mild disease. We have seen a toxic, divisive culture where some people advocate that physicians should not treat unvaccinated individuals, which is malevolent and disgusting. This type of medical discrimination could set a dangerous precedent. Do I have the right to refuse treatment to a patient involved in a motorcycle accident because I think motorcycles are too dangerous and people that ride them are being unnecessarily careless? Are we not obligated to treat emphysema, chronic bronchitis or lung cancer in patients that smoke? Smoking is universally understood to cause significant health consequences and physicians routinely educate their patients about the dangers, but some patients still choose to selfishly indulge. Can we refuse venereal disease treatment to polygamists?

Practicing medicine via oversimplification and absolutism produces standard care practices and ignores individualized patient needs.  Universal, mandatory “vaccination for all” is the epitome of oversimplification and absolutism. Clinical practice guidelines have been useful in developing strategies for treatment of common causes of certain diseases, but this doesn’t mean that we should treat a specific disease as it has manifested the same way in every patient.  For example, common practice and first-line treatment for hypercholesterolemia is a HMG-CoA reductase inhibitor (statins). Statins do work well for people that hyperproduce cholesterol, but not for hyperaborbers. In order to identify patients that would respond well to statins, we need to know if the patient is a hyperproducer or hyperabsorber of cholesterol. Elevated desmosterol levels would indicate hyperproduction of cholesterol, while elevated phytosterol levels would indicate hyperabsorption; blocking synthesis of desmosterol in a hyperabsorber (elevated phytosterol levels) would be detrimental to their production of steroid hormones (estrogen, progestins, testosterone, cortisol, aldosterone, etc.) as the phytosterols are poor precursors for steroid hormone production and potency.  However, we have chosen the “statin for all” as our initial approach; often never providing an ultimate solution for the patient’s biological aberrancy, but ordain them to pharmacological dependence in perpetuity. For the hyperabsorbers, a bile acid sequestrant, like cholestyramine, would be more appropriate. One key to making sense of the universe is knowing that the answers we get are dependent entirely upon the questions we ask. We’d better be asking the right questions before we conclude we got the right answers. Often instead of getting laboratory results and acknowledging how high the value is, we need to understand WHY the value is what it is. There are myriad reason as to the cause.  Understanding WHY will determine our treatment direction. Targeted trial therapy is far superior to generic “trial and error.”

Falsification of evidence in science can occur in two ways; 1. overt fraudulent reporting of the results (uncommon); 2. inadequately understanding the background. Our COVID story has been riddled with mishandled information and a murky background understanding.  In the general population, we identified the virus through ultrasensitive PCR testing (I have written about this in a previous blog — A 30,000′ View), which catches way too many asymptomatic individuals and therefore overrepresented presence of illness. A positive PCR test (presence of virus) is not synonymous with symptomatic disease.  Producing this falsified, artificial background has provided much of the lay public with a false understanding of the true reproductive rate of the virus.  The Pfizer, Moderna and Janssen studies identified SYMPTOMATIC disease, not PRESENCE OF VIRUS.  There is a clear distinction between these two outcomes.

Moving forward, we need to acknowledge and respect those that choose to rely upon their God-given immune system, rather than a rushed, unfamiliar, new technology for vaccination. Alternate, successful treatment strategies would also greatly benefit those with a lethargic immune response to the vaccine. Realizing that antibody production wanes in the elderly population, protein-calorie malnourished individuals and other immunocompromised states make it more important to discover therapeutic treatment options. As physicians, we need to respect our patients’ lifestyle choices and provide a service to them, without judgment, that allows them to live their lives freely and return them to the activities they enjoy. It is not our position to be authoritarian dictators to our patients; we provide information, to the best of our ability, and let them decide how much violation to their body they are willing to accept to obtain a desired result. “My body, my choice,” has been used (although I would argue inappropriately) vehemently for women’s reproductive rights, but this same ideology is not applied to mandated COVID vaccines, which is profound cognitive dissonance. If individuals don’t have the right to determine, with informed consent, acceptance of a treatment (their body), then we have completely destroyed our social culture and given credence to our government that they know what is best for us. Benjamin Franklin aptly said, “Those who can give up essential liberty to obtain a little temporary safety deserve neither liberty nor safety.” Freedom is not often lost through large, overt political overreach, it occurs in slow, incremental, deliberate steps; after decades of small, seemingly meaningless concessions, one day you’ll wake up and wonder where your freedom went. Questioning arbitrary, authoritarian rules should not be discouraged, especially when they do not apply to the dictators formulating them.