First, there are the pre-clinical studies to establish whether the illness produces an immunological response that might be duplicated by a vaccine. An animal model is found in which the vaccine may be tested. The animal is vaccinated, then later exposed to the virus to see if the vaccine induces a response as did the virus itself. For Covid, this phase was essentially skipped altogether.
Next comes the Phase 1 trial. This usually involves 20-100 people who are given the proposed vaccine to see if it induces an immune response. Even if one is seen, this does not necessarily mean that it will provide immunity to the virus. If Phase 1 is successful we move on to Phase 2.
Phase 2 trials involve a larger, but still relatively small, number of subjects, typically several hundred. Now, we are looking for a potential (but still unproven) immunity but also for common, serious side effects of the vaccine. Infrequent, negative effects may not yet appear.
Once Phase 2 is complete, we enter Phase 3, which is where we are today with the Pfizer and Moderna vaccines. Now, we are vaccinating tens of thousands, if not hundreds of thousands of people and can begin to determine real life effectiveness and safety. The current Covid vaccination programs are basically a huge experiment, perhaps the largest in human history.
The usual time frame to go from pre-clinical testing to Phase 3 is 15-20 years and the cost is $1 billion.
We identified the genetic sequence of SARS-CoV-2 in January 2020. The name stands for Severe Acute Respiratory Syndrome-Corona Virus-2 (there is a SARS-CoV-1, which also originated in China in 2002). It is the virus that causes Covid-19. It is a messenger RNA (mRNA) virus, which means it must enter the host cells and use the host’s DNA to reproduce itself.
Because of the severity of the Covid-19 pandemic and the call for aggressive measures to combat it, the Trump administration authorized Operation Warp Speed (OWS). This basically eliminated the financial and legal risk for pharmaceutical companies to develop a vaccine at unprecedented speed. OWS eliminated pre-clinical studies, paid the costs of producing the vaccine, and covered the possibility that millions of doses might need to be discarded if it proved ineffective or dangerous. Emergency use authorization gave pharmaceutical companies legal immunity for adverse effects. All of this moved vaccine trials from Phase 1 to Phase 3 in just over one year. Many regarded this as impossible a year ago.
So far, the two main players have been Pfizer and Moderna. Both produce an mRNA vaccine, a vaccine type which has never been used before. You are vaccinated with genetic material from the virus, which enters your cells. Your cells then produce the viral protein coded by that genetic material, which is released into your blood and your immune system then takes over and produces antibodies to it. When you are exposed to the real virus later, the antibodies will inactivate the virus and you either don’t get sick or at least don’t get very sick. At least that is how it is supposed to work.
Do the vaccines work? That is an excellent question. The companies claim 90% effectiveness, which would be remarkable. Flu vaccine effectiveness varies annually from 30-80% effective. Since we are still in Phase 3 trials, the actual effectiveness has not been established. Offit believes it will be very effective.
I have had a number of questions about the vaccine(s). I have listed them below.
- How long does immunity with these mRNA vaccines last? According to Offit, this has not been determined. He believes it will last one or more years, but may require boosters.
- Will the vaccine(s) reduce transmission of the virus from a vaccinated individual to someone else? The answer is, we don’t know.
- What about antibody-dependent enhanced response? This was not addressed in the interview but the concern has been raised as to whether some vaccinated individuals may experience a more extreme, potentially dangerous immune response when exposed to the virus later. The answer to this is, we don’t know. This last question is rather important. Why? With SAR-CoV-1, the coronoa virus that came out of China in 2003, pre-clinical studies to develop a vaccine were done in ferrets and rats. Vaccinated ferrets that were later exposed to SARS-CoV-1 developed a severe hypersensitivity response to the virus that led to severe lung damage. A similar experiment in mice led to severe liver damage. The researchers concluded: “Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/?fbclid=IwAR3ENojaRUgTsEgnfjypsVJVE-REgmklHbEhLw73aLklFydtbTykYUWu81U. With Covid-19, we have thrown caution to the winds.
In addition to the mRNA vaccines from Pfizer and Moderna, there are three other classes of vaccines, using a different technology, under investigation. Vaccines have been developed in Russia and China. Offit states that data on effectiveness and safety of these is lacking, even though they are already in use in those countries and others, such as Venezuela. One company, Novavax, has a vaccine in the pipeline that is in Phase 3 trials in the United Kingdom and has proven to be 89% effective, even against the new variants of the virus. It uses well established technology to stimulate an immune response to the protein on the virus that allows it to attach to human cells. This is the same technology used in the shingles and HPV vaccines, that have been shown to be safe and effective. Offit feels this will be the safest for the elderly.
Finally, Attia asked Offit the question I was waiting for: will he get one of the current vaccines? His answer was, “Not until I see the data,” meaning he will wait until there is a period of at least 2-3 months after the second dose in enough people to determine safety and effectiveness (this interview was recorded on November 16, 2020). Offit is 69 and in good health. He also believes that the vaccine(s) should not be mandated because of the unique and experimental nature of them.
My position on vaccination for Covid parallels that of Offit and Attia. I want to see better proof of safety and effectiveness and, like them, am waiting for more numbers. There are plenty of people who will willingly get vaccinated due to their increased risk for Covid complications or simple fear, despite being at low risk, so that this information should not take long to accumulate. I have no fear of Covid personally and am in no rush to be among the first to be vaccinated.
Update to my blog post, 24 February 2021: By the time I watched the interview, which was done November 16, and posted this, nearly three months had passed. I emailed Offit and asked him if his position on getting vaccinated had changed. It had. He said he received the Pfizer vaccine. He chose this over the Moderna vaccine simply because it was the one offered to him. He regarded both as essentially equal. As to Attia, of February 14, he and his wife had received their first dose of one of the two current vaccines; he did not specify which one. He stated that he felt his parents and his patients should be vaccinated as well.
Based on this, I initially modified my stance against vaccination. I looked into availability of either of the two vaccines and found that it was very difficult to find locations where I could get my first dose. That wave was essentially over and everyone was now getting their second doses. Reactions to this were generally more severe than to the first dose, as predicted. I would have had to travel for over an hour to some place where first dose vaccines were being offered. I chose to wait. Why?
I still find that I have concerns. While I respect Attia and Offit and their diligence and expertise, both admit that they were vaccinated despite some questions remaining. They weighed the risk/benefit of getting Covid against the vaccine, and the vaccine won. I remain unconvinced. Right now, the biggest concern about Covid is less dying from Covid then developing a vasculitis, which can cause potentially serious long term probems.
The infection/death ratio from Covid in healthy individuals of any age is now quite low, and dropping, to where it is close to that of seasonall flu. Covid is unusual, however, in causing, in a few individuals, an inflammation of blood vessels, called vasculitis. Because blood vessels are in every organ in the body, this may explain the array of problems that have been associated with Covid in some people, including long term respiratory, heart, GI, and kidney problems. While uncommon, this is a concern.
I believe that this is, in large part, due to the passive approach we have taken to treating early Covid symptoms. Even now, many, if not most, physician still choose to not treat patients with early Covid symptoms. They are sent home and told to the go to the emergency room at the hospital if they become really sick. This is crazy. There is sufficient hard data on Ivermectin to recommend it to anyone with early Covid. It has demonstrated high effectiveness and almost no down side. We also now know that steroids place a big role in Covid treatment. They can reduce the potentially harmful inflammatory response which may lead to vasculitis. Some of this is supposition, but so is much about the vaccines.
I still have concerns about the mRNA vaccines by Pfizer and Moderna that have not been fully answered and I realize that it may be months or years before all of these are answered. I am not looking for absolute certainty before I seek vaccination but, just as Covid is not the flu, exactly, the Covid vaccines are not like the flu vaccine, which I get annually without a second thought or any concern. I am still not overly concerned about my own risk of serious disease from Covid and have taken precautionary steps. My wife and I are taking 15 mg Ivermectin weekly according to protocols established by Frontline Covid-19 Critical Care Alliance. If we become ill, we will increase the dose to 15 mg daily for 5 days. I keep a steroid dose pack at home as well and will start that if I become sick. For now, I have chosen to wait and see how the timetable for the Novavax vaccine is shaping up. Time will tell if my approach is the right one.
Richard T. Bosshardt, MD