If you had the chance to be among the first to receive the coronavirus vaccine, would you sign up?
Before you answer, consider a few aspects of Covid-19 infection. By now, it is pretty clear that not everyone responds the same way to the virus. Most concerning is not the direct effects of the virus, but the body’s reaction. By now, you may be familiar with the “Cytokine Storm,” which give a name to the body’s self-destructive immune reaction in the lung. The devastation results from the body’s cytokine reaction to the virus, not the virus’ direct effect on the lung.
If you have watched my previous video, you understand that devastating reaction comes from suddenly upsetting a delicate balance the body has long-established. People who are physically fit do not have an imbalance in the Renin-Angiotensin system. The Renin-Angiotensin system can be thought of like a scale. When I went to medical school, we were taught this was simply a blood pressure control system. In the last decade, we have learned that it is not only tied into metabolism, but plays a key role in adjusting inflammation.
For people with obesity, hypertension, diabetes, lipid abnormalities, or inactivity, a careful and constant ACE/ACE2 rebalancing has been taking place in the Renin-Angiotensin system over many years. Take someone who has high blood pressure as an example. They have an imbalance which can be partially addressed on the left side of the Renin-Angiotensin scale below by an ACE inhibitor drug. ACE stands for Angiotensin Converting Enzyme.
Almost three-quarters of people with hypertension are treated with an ACE inhibitor. You may recognize the names, Captopril, Enalapril (Vasotec), Lisinopril (Prinivil, Zestril). The disease called hypertension is only partially addressed by ACE inhibitors, because the disease isn’t simply a “high blood pressure” problem. Fixing blood pressure is a superficial fix to a deeper metabolic problem. We can regard these drugs as acting on the left side of the scale, adding chips to the left arm. Hypertension still requires counterbalancing on the right arm of the scale, the ACE2 side.
The same can be said about obesity, diabetes, and high blood lipids. These metabolic stressors require the body to “up the ante” by counterbalancing, adding chips to the right ACE2 side of the scale. The ACE2 arm can be thought of as protective. ACE2 activation results in vasodilation, i.e. wide-open blood vessels, anti-inflammation and anti-oxidation. The problem suddenly arises when ACE2 are consumed by coronaviruses. The scale suddenly swings wildly to the side favoring constricted blood flow, raging inflammation and free radical proliferation.
In targeting ACE2 as a binding site, Covid-19 (click here to read more) suddenly upsets a fragile and precarious peace where the ACE and ACE2 chips are stacked high on both scale arms. Take away ACE2 chips, and a raging cytokine storm cascade of blood clots, blood vessel inflammation, lung, kidney and heart failure results. How does this relate to vaccination?
Vaccination is by definition, a deliberately provoked inflammatory reaction. It provides the body with a mini-preview of events to come. The general idea underlying vaccination is when Covid-19 later comes knocking, the immune system already has a playbook repertoire established. Whether the vaccine does this by tricking the body into responding to fragments of faux virus (mRNA vaccines) or inactivated viruses, the goal is to prepare a defensive playbook through a dry run.
The easy job for vaccine manufacturers is to create the antigen, otherwise known as the fake pieces mimicking the virus. We have tests that can determine whether the resulting antibody can neutralize the virus. However, researchers must rely on animal testing to gauge the inflammatory reaction which produces the virus-neutralizing antibody. By the time the vaccine is ready for humans, this inflammatory fine-tuning has been calibrated.
The hard part for the manufacturer comes when figuring out the dose which takes into account the necessary antibody and the tolerable level of inflammation. Everyone has experienced the resulting inflammation from a vaccination: soreness at the injection site, feelings of tiredness, generalized aches, headache, or fever. Increase inflammation and the side effects of the vaccine likewise become increasingly severe.
Shingrix, the most recent shingles vaccine, for example, has an artificially created portion of the chickenpox virus. This antigen is not infectious. Like the crispy outer coating of a piece of fried chicken, the bone and meat have been previously engineered out. In the case of shingles, this is antigen alone is insufficient to create immunity. The manufacturer therefore adds something called an “adjuvant”. This “adjuvant” boosts the immune reaction, not unlike increasing the dose of antigens in the vaccine. Through sequential rounds of animal tests, the final vaccine dose is designed to give most people immunity to shingles, with a tolerable amount of immune side effects.
So why is it so hard to make a vaccine? Making a vaccine is easy, but making a vaccine that is both safe and effective is much more difficult and time-consuming. Safe requires establishing safety not just for your grandson and your grandmother, but in the person taking the statin and the person taking the ACE inhibitor, among many others. This is because of foreseeable and untoward side effects.. Making a safe and effective vaccine is not only difficult but time-consuming because of foreseeable and untoward side effects, immediate and down the road.
Effectiveness has a major pitfall — age. At both ends of the lifespan, infants with immature immune systems and elderly, respond less vigorously to vaccination compared to during the intervening years. Older people suffer from shingles because their immune system responds more sluggishly and weakly over time.
There is a problem here, a trade-off between what is safe and what is effective. The vaccine creator must give the minimum dose which provides nearly 100% of people with a suitable inflammatory response. In Covid-19, the very group in need of protection is the group least able to mount a protective antibody response and therefore needs the number of antigens increased.
The same group who are at-risk for Covid-19 complications, hypertension, lipid problems, obesity or diabetes, delicately balancing ACE against ACE2 may suffer the same problem when it comes to the vaccine. Even a simulated Covid-19 attack might be enough of a strong push to suddenly upset the scales between ACE and ACE2.
Take a look at the dosing diagram again. I have drawn the the two vertical axes with a dotted line. The two vertical lines may not line up such that a “just right” zone may not exist for some groups. History is littered by vaccine projects which have never reached a wide audience. The RSV (Respiratory Syncytial Virus) vaccine, which did not have a “just right” zone. Some vaccinated children suffered a more severe pneumonia than the unvaccinated group.
Understanding these constraints, it becomes easier to grasp the understated, yet daunting challenge facing coronavirus makers working against an abbreviated testing timeline. Testifying before a U.S. House Committee, Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine warned, “I understand the importance of accelerating timelines for vaccines in general, but from everything I know, this is not the vaccine to be doing it with.”
Dr. Hotez should know, having worked on the development of a vaccine for the earlier epidemic coronavirus that caused SARS. He discovered that some vaccinated animals developed an even more severe SARS infection (Severe Acute Respiratory Syndrome), compared with unvaccinated animals following exposure to the virus. The SARS virus shares virtually the same outward (antigenic) appearance as the Covid-19 virus binding to the same ACE2 receptor.
This may well be the reason why labs see a muted, relatively short-lived antibody reaction to Covid-19 infections. The body may be refraining from mounting a robust reaction which could result in a self-on-self internal conflict. Remember, there is no “Undo button” when it comes to a needle injection.
A major setback in vaccination in the public eye might not take more than a 1% fatality or 10% severe reaction rate. Accelerated testing greatly shortens our ability to predict immediate side effects, not to mention long-term effects in those with precariously perched metabolic systems.
To this, let me add another variable to the risk calculation. If we were to eventually learn that many more have been silently infected, lowering official Covid’s Case Fatality Rate (CFR = the number of deaths divided by the number tested) to 1%, how many of you will tolerate a vaccine accompanied by only slightly fewer side effects compared to taking your chances with the disease? At what risk level would that be? Certainly not 1%. How about a vaccine-related death rate of half that, a quarter of that?
Yesterday’s report of Moderna’s success on select eight test vaccine subjects do not represent humanity’s spectrum. Those most at risk for Covid-19 complications will probably be least responsive to the vaccine or most likely to suffer vaccine complications.
This cautionary tale doesn’t mean that I endorse anti-vaxxers. That isn’t my intention. My goal is to temper the seemingly unbridled faith which presumes an inevitable safe, effective and timely vaccine for Covid. If our public policy goal of quarantine and contact tracing is to buy time for such a vaccine, maybe we should be considering other Plan B’s, now that you have heard several reasons to expect vaccination setbacks.
So what is “tried and true” among the Plan B’s? I believe we need to focus on actionable plans which do not rely upon the belief that a safe and effective vaccine is forthcoming. Don’t let the time sheltering pass you by. So let me finish by suggesting watching my earlier video, whatever your present risk factors, you can without a shadow of a doubt, improve your chances of a better Covid outcome — with exercise.
Addendum: After posting this story, Moderna released details of preliminary results for 18–55 age bracket results and for mRNA-1273 dosage 25–250 µg reactions. Going forward, the company will test 25–100 µg doses based on the antibody responses and adverse grade 3 systemic reactions at 250 µg.
