Hi, friends and families…
By now, I’m pretty sure that most of you heard the news that the FDA approved the first vaccine for COVID-19 on Friday, and that vaccinations will start in the next few days. For the details about getting your own family vaccinated, I defer to your pediatricians and other primary care physicians. But I wanted to do my best to provide some background information for you, as you read about these vaccines in the coming months. And I apologize in advance - this blog entry is both too long to be an easy read, and too short to even scratch the surface of this incredibly complex field!
The first and most important thing to keep in mind is that more than ever, the habits that we developed over the past year are still CRUCIAL to keep sickness, hospitalizations and deaths to a minimum. Mask usage - the number one thing that every person can do to control this pandemic - is extremely important whenever in public near other people or with anyone outside your immediate household. Remember, this isn't just about your individual risk, but about limiting circulation of the virus in the community and reducing risk for vulnerable people you may never meet. Hand hygiene and social distancing when appropriate are also great tools to fight COVID-19. Even with an incredible and unprecedented effort to manufacture and distribute these vaccines, it will be a long time (possibly not until late next year) until enough of the country is protected to start backing off on these measures. To put this into context, the Institute for Health Metrics and Evaluation projects that by the end of March, vaccinations will save 25,000 lives in the US, while broad mask usage would save over 50,000.
Second, testing is also still important, especially for in-person groups like schools. There are a number of testing strategies that have been developed over the past few months, and they have been really helpful in keeping outbreaks contained and preventing wider spread of the virus. I provide PCR testing in my office (lab turnaround is now running around 24-48 hours) and we expect our large shipment of the rapid (15 minute) molecular test kits any day now. Follow me on Instagram (@snotdoctor) to get quick updates on their availability.
The third thing to keep in mind is that these vaccines were developed incredibly quickly, and the disease that they target is brand new. Unlike traditional vaccine work, where doctors and scientists have many decades of data about the germ and natural immunity after infection, we are still learning about COVID-19 every day. So when a vaccine manufacturer says that a vaccine is “effective”, that really means that it’s effective in keeping you from getting sick after being infected. Because of the need for quick answers, the initial research looked mainly at that, rather than the vaccine’s effect on how contagious you would be if you got infected with the disease. We still don’t know that second answer, and we may not know if for a long time. It will require careful study of infection and death rates after enough people are vaccinated. The idea of “herd immunity” means that by vaccinating a certain percentage of the population, you also help the unvaccinated stay safe by reducing the chance of transmission. Right now, a common estimate of that percentage is 70% for COVID-19, but even after you receive a vaccine, it will still be very important to avoid spreading the infection.
Now let’s talk a bit about the vaccines themselves. As you probably know, vaccines are materials introduced into the body that generate something called an immune response, which makes the immune system develop defenses to a specific germ - a virus or a bacteria. There have been four main approaches to the development of a vaccine for SARS-CoV-2, the virus that causes COVID-19.
Whole virus vaccines use a weakened or dead virus to induce the immune reaction, while avoiding the potentially deadly infection. These have been around for a while (e.g. vaccines for measles, polio and flu), so we have a lot of experience manufacturing and regulating them. But the weakened virus can be dangerous to some people, and they require very cold storage which makes distribution a problem. Plus, production requires working with large quantities of viral cultures.
Subunit vaccines (e.g. whooping cough, hepatitis B or shingles) just deliver a part of the virus to generate that immune response - in this case, the “spike protein” that coats SARS-CoV-2. In a leading subunit vaccine for COVID-19, the protein is carried on a tiny synthetic particle. They are safe but they may not generate a very strong immune response on their own and often require additional agents and boosters. The spike proteins themselves are harmless, there is no risk of having them in your body to train your immune system. Also, these vaccines contain no genetic material.
The other two approaches - nucleic acid and viral vector - involve working with the genes of the virus to get that immune response to happen. Nucleic acids (the “NA” in mRNA, RNA and DNA) are big molecules that living organisms use as “instructions” for building proteins that make up other parts of the cells. The instructions are broken up into long segments of these molecules called genes. In humans, the instructions are coded in DNA, while in the SARS-CoV-2 virus that causes COVID-19, they are in RNA. These two new types of vaccine both “trick” the body of the person receiving them to serve as the factory for producing the viral protein that then trains the immune defenses.
The two leading nucleic acid vaccines for COVID have been mRNA vaccines, which are made by starting with a bit of synthetic RNA that has the gene for a viral protein (the current ones target the spike protein). That RNA is wrapped up in some fat to prevent the immune system from destroying it before it can work. Then, it gets inside cells in the body, and the cells follow these instructions and start making those spike proteins.
While the COVID-19 mRNA vaccines are the first of this type to complete testing for use in humans, the technique has been in development for about 30 years. By the time the pandemic arrived, researchers had been building systems that - given the genetic sequence of a specific virus protein - could quickly synthesize the mRNA that codes for that protein. When scientists in China published the genetic code of the newly detected virus on January 10th, 2020, within minutes these mRNA labs began working on a vaccine, leading to FDA approval for clinical use in 11 months. In comparison, the previous speed record from discovery of a virus to an approved vaccine was over 4 years.
Viral vector, the other genetic approach to a COVID-19 vaccine uses a relatively harmless germ (for example, something called adenovirus) to get that spike protein gene into the body’s cells. Instead of just sending it in wrapped up in a layer of fat, the gene is spliced into the DNA of a virus like the one that causes the common cold. This is another effective way to ramp up production of the protein that teaches your immune system how to fight SARS-CoV-2, since viruses are naturally good at getting into our cells. Some viral vectors can actually replicate in our bodies, further amplifying protein production, but the leading one for COVID-19 does not do that.
Unlike mRNA vaccines, some viral vector vaccines have previously been approved for human use (like the Ebola vaccine), and there are other adenovirus vaccines in clinical trials. One downside of this approach is that some people have immunity to the virus that is bringing in the spike protein gene, from previous similar infections.
Currently, there are 58 COVID-19 vaccines in various stages of testing - see this excellent page from the New York Times if you want to get details about all of them and track their progress. A small number have been approved for use outside of testing, with others close behind. And obviously, there are a lot of very complex logistics about how these are produced and distributed, as well as ethical and practical questions about who gets vaccinated when. But this week’s news is fantastic, and these vaccines are a big step toward getting this pandemic under control and returning to “normal”.
The first COVID-19 vaccine approved by the FDA for use in humans beyond the testing phase is an mRNA vaccine jointly developed by Pfizer and the German company BioNTech. The UK gave emergency use authorization (EUA) for this vaccine on December 2nd, and the US FDA did the same on Friday, December 11th. It is 95% effective with two doses, but it requires very cold storage (-94° F) which makes distribution difficult. There are a few Chinese and Russian vaccines that have been approved elsewhere in the world, but concerns remain about their safety and efficacy.
Another drug company - Moderna- has worked with the National Institutes of Health and developed their own mRNA vaccine. They have also applied for EUA, and the FDA will be considering this request on December 17th. This one has the advantage of requiring much simpler cold storage (-4° F) than the Pfizer vaccine - a standard commercial freezer would work. It also has around 95% efficacy.
Two of the leading adenovirus vaccines may be approved soon as well, and these are stable in a regular refrigerator. One was developed at Oxford University in partnership with AstraZeneca, and another by Johnson & Johnson, working with a lab at Beth Israel medical center in Boston. There is also a subunit vaccine that is fairly close to completing clinical trials, made by Maryland-based Novavax.
So stand by for more information from your kids’ pediatricians or from your own primary care docs. The rollout will be complex with unanticipated hurdles along the way. But I do have faith in the safety and efficacy of the vaccines and in the process, and I plan on getting one when I can. Even though they were developed faster than any in history, the various phases of the clinical trials were not cut short. Extensive research and analysis by some of the smartest scientists in the world was done before even considering any form of authorization by the FDA. Believe me, even though the pandemic itself is a huge crisis, no one wants to get this wrong.
Once more - mask up, wash your hands, watch your contacts and take this very seriously. Doctors have gotten a lot better at treating the sickest COVID-19 patients over the past year, but the pandemic is not going away. We have been losing around 3000 Americans a day over the past week to this disease, and we have yet to see the surge from holiday travel, get togethers and the cold weather pushing more and more people indoors.
But Spring is coming and the vaccines are coming. We can do this.
I wish you all happy holidays and a healthy new year!
Michael Rothschild, MD