Covid-19 and a Review of the Emerging Vaccine Candidates & Policies | Drink HRW

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Covid-19 Knowledge Update 8
Covid-19 Knowledge Update 8

Vaccines

For more than 20 years, there has been public debate, significant fears, and polarization in opinions surrounding an area of science that has virtually no debate within the scientific community: the efficacy and safety of vaccination. This issue emerged following the morally astounding fraud committed by Andrew Wakefield, particularly following the paper he published in The Lancet in 1998, which was since retracted. It is now known that Wakefield stood to profit from this fraud quite substantially, due to the massive payoff he received from a law firm launching a class action lawsuit regarding the MMR vaccine based on no evidence and his attempt at filing a patent on his own vaccine alternative. We may never know whether his motives were fueled by more than finances. We do know that his data was obtained unethically and without consent, then distorted and frauded, to fit the narrative he wanted. We also know that the results he reported have never been replicated, even in research commissioned by anti-vaccine organizations.

The more that Wakefield was shown to be a fraud, the more he was lauded as a martyr by a rapidly growing fringe contingent. They believed his reported results were not fraud, but rather, a cover-up by Big Pharma and the government to discredit a noble truth seeker and whistleblower. Moreover, his reports over the “issues” with the MMR vaccine shouldn’t stop there, as the cover-up would suggest that not just the MMR vaccine, but ALL vaccines were dangerous. Moreover, this conspiracy theory claimed the vaccines were not only dangerous, but also useless. Some contingents within the anti-vax community also go so far as to suppose that these childhood diseases aren’t simply harmless, but that they never even existed in the first place!

The ongoing debate described above deserves far more than two paragraphs; many books have been written on this subject. It is important to mention considering the current situation, the rush for effective vaccines, and the backlash from a growing and now significant faction within the population. Of course, there are COVID-19 denialists that believe the virus does not even exist. Then there are others that believe it exists, but that it is no worse than the flu. The common sentiment within these groups is that they will not take a vaccine, no matter what. For any would-be critical thinker, it is important to note that these anti-vaxxers immediately opposed a hypothetical vaccine before any data or evidence on their safety or efficacy existed. This is religion and belief, as opposed to critical thought and science. Compare this to the responses from science communicators, who are overwhelmingly behind vaccination, dedicating entire pages to refuting anti-vax memes, in which they would not support a vaccine until its safety and efficacy were well established.

Even Big Pharma, including the various vaccine makers, stood together against the rushing out of a vaccine to appease political pressures before its safety and efficacy were determined.1 The vaccine makers and supposed vaccine shills all reserved their opinions until they reviewed the evidence behind it; it was only been the anti-vax crew who had “made up their minds” on a subject in which no evidence was available, and who were expressing their opinions freely. The FDA has started slowing the brakes on rushing a vaccine to marker, issuing stricter requirements in early October, and is now seemingly getting cold feet over issuing emergency use approvals at all, instead contemplating the expanded access route usually preferred for investigational drugs. This is all great news, and how it should be.

In an effort to curb some of the most legitimate criticisms of the emerging vaccine candidates, for instance, regarding their timelines of development, I will first detail how abnormal it has been, and how the dramatically sped up timeline has been made possible.

Trial Phases, Vaccines vs. Drugs vs. COVID-19

Phase I of clinical trials typically involves administering a variety of different doses. It usually takes 10 years to go from preclinical to phase I human research. During the current COVID-19 pandemic, this was done in just a few months. Phase I trials in humans will not confirm immunity and will only measure antibody response. Phase I drug trials either look to simply explore safety or to evaluate clinical outcomes. It usually involves 20-40 participants.

Phase II of clinical trials usually includes hundreds of participants for vaccine evaluation, while for many drugs, this could be considered Phase III. Phase II research in vaccines looks to establish safety and evaluates the induction of a consistent immune response. Again, phase II research in vaccines doesn’t measure actual immunity. However, phase II trials for other drugs could involve 50-100+ people and begin exploring various biomarkers and clinical outcomes.

Phase III vaccine clinical research needs to involve tens or hundreds of thousands of participants. Moreover, phase III of clinical trials usually seeks to monitor efficacy of real world infection rates, and/or reduction of side effects if those vaccinated have a higher incidence of infection compared to the  placebo group. Phase III research also looks for rare side effects and will slowly scale up to hundreds of thousands, then millions, and then tens of millions of participants before mass roll out. Phase III trials in drugs can be as small as comprising 300 individuals, or as big as tens of thousands, with Phase III drug trials looking for very specific biomarkers and clinical outcomes. For both vaccines and drugs, Phase III research usually takes 15-20 years and $1b in investment to complete, when considering the start of preclinical research until the end of Phase III research. In COVID-19 vaccine research, this phase is now completed for numerous vaccine candidates in less than a year.

How are COVID-19 Vaccines Developed So Fast?

The main reason why the timeline has been sped up is that the U.S. and other world governments took on significant financial risk by pre-purchasing vaccine candidates and guaranteeing that the pharmaceutical companies wouldn’t lose money from mass producing vaccines that may end up in the garbage. This was a big risk, as the people stood to foot the bill if development went haywire, not the pharmaceutical companies, and yet the pharmaceutical companies still stand to make profits. In the interest of public safety, it was a justifiable move, and I am adamantly opposed to the oligarchical trend our society is moving towards at a rapid rate. Credit should be given to Trump, and I am by no means a Trump supporter, for his operation Warp Speed, which largely facilitated this process and prompted other world governments to follow suit. This allowed vaccine trials to seamlessly move through phases with no timeline gaps, reducing the risk and cost for vaccine makers, as well as the timelines for completion by 10 to 20 times. As a result, we will likely have a safe and effective vaccine in less than a year from the beginning of the pandemic. This is unprecedented, but the situation demanded it.

 In all likelihood, we will have safe and reasonably effective vaccines quite soon; however, they will not be our “go to” option forever, with better and more complex vaccination strategies taking over in time. The first vaccine candidates will need to be fast tracked either for Emergency Use Authorization from the FDA, over which they seem to be getting cold feet, and which, by definition, is only given when the country is under duress and risks need to be taken. Another option, which may demand a higher threshold of evidence for safety and efficacy, is the first vaccines becoming approved under expanded use for specific populations, but not for widespread use. These first vaccines will not go through the biological license application due to time constraints and the urgency involved, with the alternative routes being necessary, as the FDA does not license products studies for this short amount of time.

Luckily, the FDA has help in the form of an expert advisory committee of 15 selected individuals, made up of academics and physicians, which is helping to determine the safety and efficacy of the various vaccines. Let’s take a look at the front runners in the vaccine race, and then move on to some of the other big players.

Pfizer and Moderna

By now, you have probably heard about the two front runners in the vaccine race, the Moderna and the Pfizer vaccines. Moderna is boasting a claim of 94.5% effectiveness for its vaccine based on data from 30,000 participants, while Pfizer is claiming over 95% effectiveness based on data from 60,000 participants, in addition to the laughable statement that I’d consider hyperbolic if it didn’t come from the CEO of Pfizer:

“I believe this is likely the most significant medical advance in the last 100 years...”

Pfizer Chairman and CEO, Dr. Albert Bourla 

The good news is both Pfizer and Moderna have been transparent, releasing their vaccine protocols. Let’s take a look at why the Moderna and Pfizer vaccines were first to be developed, and why they are so similar to each other in terms of efficacy.

Both vaccines rely on messenger RNA (mRNA) technology. There are various ways to design vaccines; some are more difficult to design and manufacture, while others are relatively fast and simple, with the simplest being “genetic plug and play” vaccines which deliver the mRNA of the coronavirus that codes the spike protein responsible for attaching itself to the human body. In turn, the body ends up making the viral spike protein, with the immune system making antibodies against it. There are slightly different mRNA constructs in each vaccine, and the Moderna vaccine contains 100 mcg per dose delivered over two doses, and the Pfizer vaccine contains only 30 mcg per dose delivered over two doses.

Now, here are some of the differences. The big difference is that Moderna’s vaccine needs to be stored at -20°C instead of at -70°C, making logistics much easier. On the flip side, Pfizer’s production capacity is much greater, meaning more people will have access to the Pfizer vaccine faster.

There’s a very small chance, unless I am misinterpreting this (which is a possibility), that both of these vaccines may lead to positive PCR tests for COVID-19, as mRNA replicates itself in the body, although it is expected to be quickly broken down. The current  PCR COVID-10 test sometimes fail to detect the virus, and detects its messenger RNA instead, which is present for up to 3 months after individuals cease to be infectious. This Is because the mRNA is replicating, but it does not make you infectious, as functioning copies of the virus are not produced within the body.

Pfizer received no funding from the U.S. National Institute of Health (NIH), whereas Moderna received $1 BILLION from it, since it is a partner on its vaccine. Moreover, the NIH holds the patent on the vaccine production method used by Moderna.

Both Moderna and Pfizer have stated they will be applying for emergency use authorization from the FDA in the coming weeks; however, whether the FDA will still allow this approach is yet to be determined.

Side effects

Both Moderna and Pfizer have reported significant rates of mild side effects. In their first phase of research, 50% of participants receiving the high-dose of the Pfizer vaccine experienced side effects such as fever. Pfizer’s data has continued to identify fever and aches in a significant portion of people, although there are currently no serious safety concerns.
Moderna has also reported pain at the injection site, fatigue and aching muscles and joints as the vaccine side effects, although the data safety and monitoring board did not identify any significant safety concerns.

Both vaccines may lead to unpleasant side effects, which some may call “COVID-19-like side effects,” but it is important to note that the vaccine cannot give you COVID-19; it is simply leading to an immune response, which expresses as its symptoms. The immune response will not become as serious as a COVID-19 infection could potentially become, and you will not become infectious. These side effects are simply your body mounting an immune response, which is how the vaccine works.

Takeaway

 

We do not know how long the Pfizer or Moderna vaccines will be effective – maybe a few months or even a few years. We also do not have the regular safety data we usually get from testing vaccines. Is it worth the risk? Most experts believe that it is, and I would agree. Serious side effects of vaccines are incredibly rare – usually, they are in the range of 1 in a million or lower for most vaccines, despite what anti-vaxxers will tell you.

 

Johnson & Johnson, AstraZeneca, CanSino and the Russian Sputnik V

Rewinding back to spring 2020, these four vaccine manufacturers were at the forefront of the news. They were fast moving, but slowly, all have begun faltering and losing steam. Trials carried out by Johnson & Johnson and AstraZeneca were paused due to potential serious adverse events. In the AstraZeneca trial, the research was first paused in August, when a participant developed multiple sclerosis; then, another participant developed transverse myelitis, which is inflammation of the spinal cord in September, resulting in another pause. The case of multiple sclerosis was determined to be unrelated to the vaccine; however, transverse myelitis and multiple sclerosis have the same mechanisms of disease development, with transverse myelitis often being the first symptom of multiple sclerosis. Transverse myelitis is a rare condition occurring in 1 per 200,000 individuals, so the observed sudden onset in the trial participant is rather worrying for the safety of AstraZeneca’s vaccine. It was first reported that Phase I and Phase II data showed that the AstraZeneca vaccine did not work very well in individuals aged over 55 years, but AstraZeneca is now reporting that their vaccine elicited a strong T-cell response in elderly individuals, and that there were no serious side effects. They have projected full results becoming available around Christmas time. This means that they do not consider either of the serious side effects reported previously as related to the vaccine, or even potentially related to it, which should be at least a small cause for concern. With questions on safety, and highly effective alternatives from Pfizer and Moderna, it is yet to be seen how nations will react to AstraZeneca’s vaccine submission. If the AstraZeneca vaccine does prove to be safe and effective, it is a much needed win, as the company estimates it could produce doses for 400 million Europeans at no profit by the end of 2021.

Johnson & Johnson paused their vaccine trial in mid October, following serious and unexplained illness of one of the participants; however, at this time, they did not yet know whether the participant had even received the vaccine or the placebo. Johnson & Johnson released a statement on October 23, stating they had restarted recruitment after the “unexplained illness,” which remains unspecified, that could have arisen from “numerous causes,” and also adding that there is no evidence it was the result of the vaccine. This is important, as that acknowledges the fact that the individual who became ill received the vaccine and not the placebo. Johnson & Johnson has not released any further data on its vaccine’s safety and efficacy, but did state on November 17, 2020 that they expect to submit the vaccine for FDA approval by February. Considering the Johnson & Johnson vaccine trial will not be fully enrolled until the end of December, they are putting the cart before the horse and presuming that:

  1. Their vaccine works
  2. Their vaccine is safe

We will see in early 2021 if their vaccine is, in fact, safe and effective.

The CanSino vaccine( CanSino being a Chinese Pharmaceutical company) has gone through an odd road. First, Canada announced a partnership with CanSino, which fell apart in the summer, when Chinese officials refused to release the vaccine for export to Canada, where clinical trials were set to begin. CanSino has shifted gears and launched clinical trials in countries such as Russia, Pakistan, Saudi Arabia and Mexico, while simultaneously gaining approval to be administered to the military in China. There is little knowledge regarding the safety and efficacy of the Cansino vaccine; however, many experts have doubts regarding its efficacy.

All three of these vaccines have one thing in common: they are utilizing adenoviral vector technology, which uses a genetically modified cold virus. It’s important to note that this technology is over 30 years in the making and has not yet yielded an effective vaccine for humans. The technology works by making the genetically modified virus replication defective, meaning that the goal is to make it unable to replicate in the body and cause illness.

It is of note that the vaccine approved in Russia, based on Phase I evidence alone, utilizes this same adenoviral vector technology. Considering what Russia has actually approved it for, it seems to be an expanded use clinical trial in which high-risk individuals, such as healthcare workers, were administered the vaccine. Basically, Russia conducted a real-time phase III in high-risk individuals and healthcare workers, calling it an approval. They have now announced the results of this trial, claiming it to be 92% effective.

Sanofi/GlaxoSmithKline and Novavax

Sanofi and GSK announced Phase I/II combined trials for the fall of 2020, with the plan to move to Phase III trials by the end of 2020 if the results were positive. Apparently they were, as they have now announced that Phase III research will begin on time in Canada and the USA, so results must have been promising.

Novavax has similarly been quiet in the news, but did initiate Phase III research in the fall, set to study participants in the UK, and just recently was granted “Fast Track Designation” by the FDA, which allows a company to engage in dialogue and supply data to the FDA on a “rolling basis” to expedite approval.

Both GSK and Novavax vaccines involve the use of “recombinant protein” or “spike protein,” which involves the same mechanism of action as the Hepatitis B vaccine, the HPV vaccine, one available influenza vaccine and the Shingrix vaccine for shingles. Novavax is using the same adjuvant as is used in the Shingrix vaccine, which works incredibly well, especially for the elderly, and is safer than the live attenuated vaccine alternative. Some vaccine experts, such as Dr. Paul Offit, have previously stated that spike protein vaccines likely have the lowest chance of side effects.

MERCK Vaccine & Others

There are many other vaccines being developed that I haven’t mentioned, such as a nanoparticle-based vaccine candidate or the BCG vaccine, first used medically in 1921 and most commonly used for tuberculosis, which is a vaccine already developed that has shown to improve outcomes in numerous infections by training the immune system to respond to infections with greater intensity. Currently, health care workers in countries such as the UK are participating in trials utilizing the BCG vaccine for COVID-19.

One company trailing behind the other big names in the race for a vaccine is Merck. This is a company that tends to under promise in the hopes of over delivering, with daily press releases not being part of their corporate philosophy. Merck announced their vaccine strategy in May, which had been successful before:

“One of the COVID-19 vaccine candidates that Merck decided to back aims to build off the success it had with an Ebola vaccine that came to market last year. That vaccine uses an engineered vesicular stomatitis virus (VSV) to shuttle a gene for the Ebola virus surface protein into a host’s cells. Merck now plans to develop a VSV-based COVID-19 vaccine in partnership with the International AIDS Vaccine Initiative (IAVI), a nonprofit that was originally set up to push forward HIV vaccines but has broadened its portfolio to include vaccines for a wide range of other diseases.”

Merck hasn’t only been focusing on a vaccine, as they have also been developing an oral antiviral they believe will show to be superior to remdesivir, which isn’t saying much, as remdesivir has shown questionable and potentially non-existent benefits.

Challenges on Vaccine Roll Out 

There are multiple challenges regarding widespread vaccine roll outs, and whether they will help us achieve immunity. First off, it is yet to be determined whether we will need a new COVID-19 vaccine each year – we simply don’t know enough yet. We will almost certainly need booster vaccines; however, Dr. Paul Offit predicts that the vaccine will be effective for years and will not need to be redesigned every year. Eve, though COVID-19 has undergone large genetic changes in the over the last year, these changes will not impact the effectiveness of the vaccine.

Large-scale resistance to vaccinations could also contribute to their lack of effectiveness; despite a rebound from only 50% of Americans willing to be vaccinated  observed in October, only 58% of Americans are willing to be vaccinated if such an option were free and approved today. The good news is only 12% of respondents are completely against vaccination in general, with the majority believing the timeline was rushed, and wanting to wait for more safety data. Since we will undoubtedly slow-roll the various vaccines to the highest priority individuals, these “COVID-19 vaccine-hesitant” responders will get to wait and see how it goes. Eventually, we could see 75-90% inoculation rates.  Inoculation rates in this range, coupled by vaccines that are showing to be 90-95% effective, would effectively end the pandemic. Even rates of 50-60% inoculation with vaccines, as effective as the various candidates are showing to be, would basically end the need for any widespread lockdowns, and would allow for even some basic measures to turn the tide against the virus.

Slow Roll – Who Should Be Vaccinated First?

It has widely been reported that healthcare workers will be the first to receive the vaccinations; however, as stated by Dr. Paul Offit, the “tier 1” category of vaccination priority is much more broad than simply the frontline health workers. Tier 1 will include healthcare workers, other essential frontline workers, including grocery store and retail workers, pharmacy staff, as well as transportation and water sanitation personnel. In addition, anyone aged over 65 years or with comorbidities such as diabetes, obesity or COPD would be deemed a “tier 1” priority. All in all, half of the population in the USA will be deemed a “tier 1” priority. The USA, like every other country that has pre-ordered some of the vaccines such as the one by Pfizer, will only get a percentage of the total dosages available, which is a drop in the bucket when considering the quantity needed. With the few available doses that will start rolling out in early 2021, the US federal government is simply defining “tier 1” and then distributing to each state and allowing them to decide who gets first priority. This is precisely why having so many options that look to begin distribution in 2021 is great news. We need many different vaccines, not just a single provider. I’d like to see the ranking within the first tier, i.e., once an individual is identified as “tier 1,” three questions can be asked:

  1. Are you a frontline essential worker?
  2. Are you over 65?
  3. Do you have comorbidities?

Those who answer “yes” to all 3 of these question would become first roll out priority in the tier 1 phase, followed by those answering 2 of 3 questions as “yes”, and finally those answering just 1 of the 3 questions as “yes”. Roll out per phase could be conducted by random lottery. All in all, it may take as long as 4 to 5 years to vaccinate the entire world, so strap in – we have a long way to go.

Should the COVID-19 Vaccine Be Mandatory?

Vaccine mandates meant to stem public health crises is a complex debate, and I do not think there is a universal correct answer. The context of the situation is important, and I have often mused on current and hypothetical situations, trying to determine at what point mandates are necessary and unequivocally good, and at what point they are an unacceptable assault to personal choice. As for the COVID-19 vaccine, I believe any attempts at a mandate would be both incredibly foolish, unjustifiable and uncalled for.

First, any attempt at a mandate would only create further unrest within the segment of the population that believes COVID-19 to be a conspiracy and is not real, and will cause further growth of the anti-vax fringe. This could potentially negatively impact many other vital vaccination programs.

Second, I believe that a significant portion of the population (a portion large enough to dramatically reduce the burden of COVID-19 spread) will volunteer to receive the vaccine without need for a mandate. As I detailed above, there may be more of a panic among individuals impatiently waiting for their turn, rather than the need to force many people to get vaccinated.

Finally, I do not believe COVID-19 illness is serious enough to justify a vaccine mandate. This is not to say I don’t believe COVID-19 is serious; I have written a mountain of content that explicitly states I believe it is serious, perhaps 8-10x more serious than the flu, largely because we do not have a vaccine, and did not have effective drugs to treat it. As COVID-19 vaccination, by voluntary application, surpasses our standard rates of flu vaccination, just under 50% for adults aged over 50, the spread and death toll will plummet. Further, infection fatality rates are already dropping due to better treatment options, and will continue to drop more as we learn more about COVID-19. Moreover, the survivors, which make up the vast majority of those infected with COVID-19, are likely to experience less serious disease severity with each subsequent infection.

Any attempt at a COVID-19 vaccine mandate will be met with significant resistance and is ill advised. As an afterthought, if the vaccine options have variable rates of success and risk of side effects, any mandate that involves using a vaccine that is not the absolute safest option would be morally questionable.

Should We Vaccinate Children?

Aside from Pfizer’s recent approval to study their vaccine in children as young as 12 years old, the data regarding if the vaccine options will be safe and effective in children and pregnant women is currently lacking. The lack of short-term, let alone long-term data on the safety of the vaccination options for pregnant women and children poses another massive hurdle for any attempt at a vaccine mandate. Supposing this data on safety and efficacy appears, the question of “Should we vaccinate children and youth?” does not disappear. We know that COVID-19 is killing about as many children as the flu does on an average year (just over 100 from COVID-19 in the USA at the time of this writing); however, COVID-19 is far more widespread than the flu, as the flu isn’t as contagious, and we have a vaccine for it. Per case, COVID-19 is less deadly for children and youth than influenza. In this context, people under 21 make up 26% of the U.S. population, but make up 0.08% of COVID-19 deaths. Widespread vaccination of the “at risk” and adult populations will dramatically reduce the risk of children and youth becoming infected, and as such, reduce their risk of death or serious side effects to negligible levels. It is unlikely we will need to develop a COVID-19 vaccine for children, and we should question if such an option is pushed upon us.

Final Thought

Will I get the COVID-19 vaccine right away? Supposing Canada follows a similar policy to what the USA is proposing and has announced, I will not get the chance. However, if I did get the chance, the answer would be “yes.” Likely, it will be another year or longer before I get this option.

Dogmatic Antivaxxers: please do not assume I "haven't educated myself" on the subject because I do not agree with the imagined dangers propagated by many in the alternative health industry. I have, and am likely more familiar with the subject than whoever is inclined to comment. Consider the podcasts I've been on and the brands distributing the hydrogen tablets, I've heard all the arguments and debates. I also followed the subject for many years before entering into this business. I can almost guarantee you, you are not telling me anything new or anything convincing, so save yourselves the time, energy and anger.

https://www.smh.com.au/world/north-america/american-big-pharma-to-stand-against-rushing-covid-vaccine-sources-20200905-p55sol.html