COVID-19 vaccination - is it worth it?

Dear Hivers,

first I just wanted to comment on the post from @perceive about the side effects seen in the ongoing COVID-19 vaccine trials. But then the comment got longer and longer, so here are my 2c on this topic.

Actually I work in drug development, in a pharma company, so you can believe me that I know what I am talking about. And I can tell you that those chills and fever described by @perceive are quite normal. They are of course annoying, but relatively harmless. Also that a Brazilian trial subject died recently is tragic, but not worrying, as it turned out he was in the (placebo-treated) control group.
However, what is not harmless are the longterm side effect that won´t show up quickly and obviously!

^source

Our immune system is really complex and far from being fully understood. But one thing we know: it doesn´t forget things. Such harsh immediate reactions described will have in addition long term triggering effects which nobody can predict for sure. Each human has a different immune system and capability, depending on many variables, e.g. overall health state and age, but also healthy diet, low level of pollution, a well functional relationship, lack of essential troubles,.. The relatively new area of psychoneuroimmunology deals with the delicate interactions between psychological processes and and our immune system. To summarize, we can´t know for sure, in what way a boosting of our immune system by a vaccine shot triggers unwanted immune reactions. Take the H1N1 (swine flu) vaccine Pandemrix as an example.

Pandemrix was known to have much more side effects than comparative drugs even before the narcolepsy side effect was known (source)

More than 1000 children and youths in Europe had developed the very uncommon but devastating sleep disorder narcolepsy after having been vaccinated for H1N1 with Pandemrix which contains a specific adjuvant. Other H1N1 vaccines not having this adjuvant did not lead to increased narcolepsy cases. Narcolepsy is today known to be an auto immune disease. We can safely assume that with every vaccine there is - at the time the drug is used - an unknown percentage of such unwanted long term effects. So the rationale to take this risk should be better very solid!

Generally, autoimmune reactions and diseases are surging worldwide since years. So much that the pharma companies can´t fill the demand of certain drugs which are fighting these diseases, despite being partly super-expensive! A company would for sure not want to lose business by not supplying enough product, but exactly this is the case.

Why?

Pollution & unhealthy processed food and life style for sure are main drivers, but auto immune reactions from vaccine adjuvants like mercury or aluminum play a role as well, Pandemrix is only one example of several! There is even a new syndrome called "Autoimmune Syndrome Induced by Adjuvants" (ASIA), but it is until today not clear in how far this is really clinically relevant (1) and some authors conclude that current studies do not support the existence of ASIA. But to evaluate the significance of ASIA is not the point of this post. It is a whole story on its own.

The point is that due to these not well known risks only do a vaccination when the benefit outweighs the risks. Until you not belong to a high-risk group (immune depletion, cancer, cardiovasc. diseases, high age) this is not the case for COVID-19, because new epidemiologic data (e.g. (2)) show that the mortality rate of COVID-19 is not more than that of a severe flu, especially in people <70y old.

You might argue that there are drugs out there that have much more side effects than a vaccine, like used in cancer. As you know they are in part almost as deadly as the cancer itself. But in order to save a few weeks time of life, people do take them. We cannot blame them or the treating physicians, until we are in the same situation, facing close-by death. At least I am not sure if I would have the guts and say no to such drugs. I just mentioned it, because it is the severity of the disease or condition which decides what side effects one should be willing to accept. In that extreme case of a deadly disease it might be totally acceptable to take drugs which are very troubling. On the contrary, if you suffer from a tiny headache, you would never take a pill from which you will lose your hair, right?

And same is with COVID-19. The more it turns out that this is a disease like a flu, the less risks we should be accepting in the prevention of it. Especially politicians should be overly careful about the risks when they start MASS VACCINATION programs, because then even very rare side effect will accumulate in the treated population. You have to know about the rarity definitions which are worldwide standardized:

Category	Frequency	In %
Very common	≥1/10	≥10%
Common (frequent)	≥1/100 and <1/10	≥1% and <10%
Uncommon (infrequent)	≥1/1000 and <1/100	≥0.1% and <1%
Rare	≥1/10,000 and <1/1000	≥0.01% and <0.1%
Very rare	<1/10,000	<0.01%

^source

If you dose several hundred Mio people (as some politicians and profiteers wish), even very rare side effects add up. Let´s suppose 500 mio. sheeple get vaccinated (not entirely unrealistic) and let´s further suppose that the drug has a very rare, but also very serious side effect at a frequency of 1:10.000 (0,01%) - that´s quite underestimated given what was said above. Then on average 50.000 people will get this side effect! We are speaking about otherwise healthy people most of which never would get harmed from this flu-like virus but from the vaccine for sure around 50.000 people will be seriously harmed per 500 mio. vaccinated. And on top of it, the protection rate from that vaccination won´t be 100%. This again decreases the risk-benefit ratio significantly. Let´s suppose optimistically that 50% of the vaccinated people are protected from COVID-19 (assuming typical protection rates from flu vaccines and a CDC-estimate (3)), then you need to vaccinate 1000 mio. people to protect 500 mio, and will have 100.000 side effect victims! And for a still rare event with a probability of 1:1000? Then it will be already 1 Mio. adverse events in the vaccinated population! A price no responsible decision maker should be willing to pay! Well it´s rather the people who will pay the price at the end! And don´t forget, there has never been a Coronavirus vaccine. It is not at all clear that a 50% protection rate is even feasible! The clinical development programs currently ongoing hope for 60% but are satisfied, if the protection rate is >30% (4).

But how many deaths will be prevented by the vaccine? It largely depends on the efficacy of the drug (which nobody knows so far) and who gets the vaccine. Vaccinating 500 Mio. people <65y would be a desaster, as this group is hardly affected by SARS-Cov-2. Clearly, only risk groups should be vaccinated (like it is also recommended for flu shots). But here the problem is that especially in very old people and people with immune defects, a vaccination is often not effective, because you need a strong, active immune system to have the optimal triggering effect by the vaccine. Tragically, especially the groups which would profit most, are the ones where the vaccination is least successful. Besides, any vaccine currently in development for sure won´t have this vulnerable group of people in focus of their clinical trials. In case of the ongoing Moderna Phase 3 trial, patients with "Immunosuppressive or immunodeficient state" are explicitly excluded from trial participation ((4), page 45)! All this doesn´t improve the benefit-risk ratio in this group, which brings me to the conclusion that for nobody (both low- and high-risk groups) it is worth to get a COVID-19 vaccination. But hard facts we will know only years from now.

Did I mention that those very rare but potentially serious side effect are nearly IMPOSSIBLE to detect upfront in those rushed clinical trials we are seeing now? To detect a side-effect of 1:10000 that occurs within 5 years, you would need to observe vaccinated patients of at least the same number for 5 years (and even this is no guarantee you will spot it). No way, that the Authorities worldwide will wait until then before declaring the vaccine as safe.

But there is even more!

Some of the more than 150(!) COVID-19 vaccines in clinical development (for a summary see here) are even of a completely new category, gene-based or mRNA vaccines (5) (made by companies like Moderna and Curevac), which were so far never licensed in humans and where one should be especially cautious. Why? By inserting viral mRNA into the cells, they trick the body into producing some of the viral proteins itself. I for sure don´t want that my cells produce viral proteins unless it is fully explained in what ways this triggers the immune system and until long term safety follow up studies are published! Who could ensure that such a radical new immune stimulation can´t induce in a subset of recipients a much-feared cytokine storm or cancer inductions years later?
Despite the risks, they are loved by the companies and the mass vaccination promoters because they are way cheaper and quicker to produce than traditional vaccines (5).

And to make things worse, in a recent Forbes article (6) it is revealed how pathetic the trial design of several ongoing Phase 3 vaccine trials from Moderna, Pfizer, Astra Zeneca and J&J is!
As an example, in the Moderna trial COVID-19 cases are defined by these vague criteria, e.g. a positive PCR-test plus a few symptoms, nothing else, particulary no virus isolation from blood and no ruling out of another infection like flu.

COVID-19 definition in the Moderna Ph3 trial (source)

Also, already after only 53 such COVID-19 events a first interim analysis is done, and as long as 13 or less of those 53 cases were in the vaccinated group compared to 40 or more in the unvaccinated control group (which is of same size), this is considered a success already! Pfizer is even more generous in its success requirements. Their interim analysis starts after 32 vaccine recipients develop COVID-19 symptoms, with a success margin of 7 or less in the vaccinated compared to 25 or more in the control group. It is not even aimed (nor realistic) to totally prevent SARS-Cov-2 by the vaccination.
If no "success" is showable after 53 events, they check again after 106 events, and if then still no evidence, they try again after 152 events:

Event-driven analysis plan in the Moderna Ph3 trial (source)

If the "early efficacy" is shown, they will already publish the results and go with that (and without any safety follow up data!) to the Health Authorities, to get a speedy priority review and approval of the drug. Of course the study continues to follow up all vaccinated subjects for 2 years (why not longer??), but by then the vaccine is probably given already to ten thousand people or more. And remember, in case of Moderna, this is a mRNA vaccine that was never tried out in humans!! Extremely scary!

In fact, the vaccines will be so "safe" that the vaccine makers won´t cover any costs due to side-effects of their COVID-19 shots but will be indemnified in Europe and the USA (e.g. AstraZeneca or Sanofi have fixed such deals with the EU recently (7))! Don´t they trust in their own medications?? It is unacceptable that the taxpayers will have to pay those costs!

SUMMARY:

1. It is highly doubtable that the COVID-19 vaccine will be safe enough to take the risks of the vaccination, simply because there is not enough time to wait until very infrequent adverse effects will show up in clinical trials.

2. The overall mild disease COVID-19 (median infection fatality rate is 0,05% in people <70 (2)) does not require taking such risks. If you as a politician want to reduce deaths from COVID-19, it is much better to protect the high-risk group (very old and/or vulnerable people) and having them stay at home and minimize social contacts, then to risk 100.000s of serious adverse reactions from mass vaccination programs, let alone all the other, not only economic costs from the panic spread like depressions, missed focus on other diseases,...

Sources:
(1) https://pubmed.ncbi.nlm.nih.gov/25794485/
(2) https://www.who.int/bulletin/online_first/BLT.20.265892.pdf
(3) https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm
(4) https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf
(5) https://horizon-magazine.eu/article/five-things-you-need-know-about-mrna-vaccines.html
(6) https://www.forbes.com/sites/williamhaseltine/2020/09/23/covid-19-vaccine-protocols-reveal-that-trials-are-designed-to-succeed/#229516025247
(7) https://www.indiatoday.in/science/story/covid-19-vaccine-makers-see-eu-shield-against-side-effect-claims-1724398-2020-09-23

PS: The #leofinance tag was added because covid-19 and the way it is acted upon impacts the economy of our world as we know it.