COVID-19 Vaccines: Building The Plane As We Fly It

Updated: Jan 29

COVID-19 vaccines, Dr Leslie Phillips, Data-Driven LLC
Data-Driven LLC - COVID-19 Vaccines: Building The Plane As We Fly It

Early attempts at vaccination read like a script:

Imagine, if you will, centuries of human populations devastated by a virus.

No social group is spared. No country is untouched.

Except milkmaids, standing in a field, surrounded by cows….

In the late 18th century it was observed that one group of people were unlikely to get smallpox. Milkmaids, frequently infected with the relatively mild cowpox virus, were rarely sickened by smallpox. With this observation, the scientist Edward Jenner transferred matter from a milkmaid’s cowpox lesion and injected it into a healthy young boy. Two months later he exposed the boy to smallpox. No disease occurred. This experiment was the very beginning of vaccines. In fact, the term “vaccine” originates from the term vaccinus, meaning “of or from the cow”.

Fast forward to 2021 - no social group is spared and no country untouched by another pandemic: COVID-19. And finally there is a vaccine that is not from a cow, not grown in an egg, not a weakened virus but is a synthetic snippet of code. A code that instructs your body to build and then recognize the “entry key” used by the SARS-CoV-2 virus and lock it out -- and by doing so saving you from illness, maybe even death.

It’s remarkable. And exciting. And came to fruition in less than nine months. Getting a vaccine within 18 months felt like a shot in the dark and yet we have achieved these shots in arms in half that time! Yet to many, it is just a bit suspicious and, to many more, very mysterious. Below I try to answer common questions about vaccination. I will add more over time, so feel free to email me yours! And we really are building the plane as we fly it, with so much new and unknown. But all indications indicate that this plane will offer us a safe flight to our prime destination of herd immunity. Get your ticket soon. And please be patient, flight delays abound.

NOTE: Thanks to all of you who have sent questions, many are now added below as a result. I indicate your questions with an *. Given the long length of the question list, you might find it most useful to skip to those questions that are most salient to you.

That was fast, what steps were skipped? I mean, how do I know this vaccine is safe?

Indeed, that was fast -- 9 months from sequencing to shots in arms. It’s astounding really. Before now, the fastest vaccine to be developed was for Mumps in the 1960’s and that took four years! Global urgency of the COVID-19 pandemic spurred global cooperation and the rapid development of vaccines. These vaccines have undergone a rigorous process to assess their safety and effectiveness before receiving approval. A key reason for the speed was that the vaccines were being manufactured while they were being tested just in case the clinical trials showed that the vaccines worked to safely protect against COVID-19. In the case of the current mRNA vaccines, this bet paid off with impressive clinical trial results meaning that early production efforts created a deployable vaccine in record time.

The chart below shows the testing steps taken with a modern HPV vaccine as compared to the COVID-19 mRNA vaccines. Note that more participants were followed for a shorter period of time when testing mRNA vaccines. This made it easier to get clear results from the vaccine trials quickly, due to greater statistical power.

COVID-19 Vaccines, Dr. Leslie Phillips, Data-Driven LLC
Data-Driven LLC

*Why use this novel mRNA vaccine strategy when the stakes are so high?

Exactly! The stakes are so high that every day matters. Traditional vaccines involve time to grow a viral protein or a virus and that can then mean waiting. mRNA vaccines short cut that process by delivering the genetic code directly to the cell and letting the cells build the viral proteins.

How do vaccines work?

Vaccines train your immune system to recognize and fight a virus. COVID-19 attacks your cells with a spike protein that surrounds the SARS-CoV-2 virus. The mRNA vaccines use a molecule called mRNA to instruct your immune system to build a spike protein which your body identifies as an infection. In response, your immune system begins producing antibodies specific to SARS-CoV-2, and activates T-cells (cells that focus on foreign invaders) to fight the infection. All with one goal in mind: your now-primed immune system will work to fight off COVID-19 if you are exposed to the SARS-CoV-2 virus in the future.

When is my turn?

It depends where you live! Check your state’s department of health site for details.

What will it cost me?

$0.00. The federal government has paid for your dose and your insurance will pick up the administration fee. Uninsured? There’s a fund for that so even without insurance you can expect to pay absolutely nothing.

Will it make me sick?

The vaccine cannot make you sick with COVID-19. The mRNA vaccines contain a snippet of code that instructs the immune system to get to work preparing for possible exposure to the SARS-CoV-2 virus, but they carry no virus whatsoever. It is not unusual for people to get a sore arm for a day or two after vaccination and you may feel “icky” with fatigue or low-grade fever. This “under the weather” feeling rarely lasts more than a couple of days and is more common in young people and after the second dose. Think of it as your immune system gearing up for a battle it may someday encounter. Of course, people who never feel poorly after vaccination build immunity too!

Can you guarantee it is safe?

I can guarantee that the mRNA vaccines are incalculably safer than the alternative of illness with COVID-19. I can also guarantee that I will be rolling up my sleeve as soon as I am eligible. And I can show you the data that over 1% of Americans who test positive for this virus are dying from it. This virus is not safe. While most people get sick and recover, many also suffer for months after illness and as of this writing over 400,000 Americans have died. For context, that is losing the equivalent number of Americans lost in the September 11th attacks every single week until October of 2023. In contrast, no deaths or life-threatening health events related to unexpected reactions to the vaccine have yet been reported from mRNA COVID-19 vaccination despite close tracking.

But I know someone who died within a day of his vaccine and another who died that same week, how can I really feel safe?

Rare events happen and they may happen as a result of these vaccines but as we close in on 20 million doses administered in the United States alone, it is clear that safety issues, if any, will be the extremely rare exception, not the rule.

Remember, almost every American will be urged to get this vaccine and some number of those will die this year and statistically some of those will die very close to their time of vaccination -- even the same day. For instance, within the next week for every ten million 55-64 year olds in the US, 793 will die of a heart attack. These heart attacks are expected in people who are not vaccinated. Now let's say you vaccinate that same group of ten million 55-64 years olds, 793 will still die of a heart attack within the week but now that event is seen as something that happened after vaccination. We will need to study each event to make sure nothing is missed but so far there has has no evidence of adverse health outcomes or deaths resulting from vaccination.

*Has the vaccine been tested in people of color, older adults, children, or pregnant women? The clinical trial researchers worked hard to recruit trial participants who represented the age, race, and ethnic diversity of the US. This included older adults, and a wide range of racial and ethnic groups. However, children and pregnant women are special populations and were not included in the trials with the exception of 16 and 17 year-olds in the Pfizer trial. Trials that include a larger pediatric population are ongoing. The American College of Obstetricians and Gynecologists has said that there are no known contraindications for pregnancy and that COVID-19 vaccines "should not be withheld from pregnant individuals who meet criteria for vaccination" based on Advisory Committee on Immunization Practices' recommended priority groups. As part of their decision-making process, it is recommended that pregnant women or women planning to become pregnant talk to their doctor about how the known and theoretical risks of vaccination compared to the risks of COVID-19 during pregnancy

What's up with the allergic reactions?

Anaphylaxis, a serious complication, has occurred approximately in 11.5 per 1 million vaccine doses. This usually occurs within ½ hour. It’s not clear who is at risk but a history of severe allergies may be correlated with this reaction. If you are allergic to other vaccines, please consult with your doctor to determine what vaccination protocol is best for you. After you receive your injection, you will be monitored for any reactions. All vaccine sites are prepared to give you a medication called epinephrine and ensure you get medical attention should an allergic reaction occur.

One dose or two?

Two - separated by at least 3 weeks (Pfizer) or 4 weeks (Moderna). While we know that one dose offers some protection, we have sparse data on how much or how long. If we did, we’d be happy to vaccinate twice as many people twice as fast; yet it’s a gamble that most scientists do not feel is wise in the absence of data to understand whether single-dose vaccination can get us to our goal of herd immunity. To be fair, some countries have opted to draw out the interval between dose 1 and 2 indefinitely to allow more universal first-dose access. This is an area where even scientists disagree. But it's already been decided for you, so there is no need to stick out your neck on this controversy, just stick out your arm… twice! That’s the recommended FDA protocol. Of note, the CDC has said it is acceptable tp schedule your 2nd dose as far as 6 weeks past your first if circumstances dictate. This is not likely to diminish your ability to mount a strong immune response, but it will delay it. Do not assume you are sufficiently immune until you are two weeks past the second dose.

Why is the interval between doses greater for Moderna than for Pfizer? Are the 3 and 4 week intervals minimums or maximums or averages? What happens if you go longer than the stated interval, or sooner?*

The dosing intervals are based on what the companies used in their clinical trials; they became the recommended intervals based on those data. They are suggested minimums and as CDC notes, "The second dose should be administered as close to the recommended interval as possible. However, if it is not feasible to adhere to the recommended interval, the second dose of Pfizer-BioNTech and Moderna Covid-19 vaccines may be scheduled for administration up to 6 weeks (42 days) after the first dose."

To be fair this has not been formally studied but based on how adaptive immunity works, it is almost certainly the case that your body will remember the first dose of vaccine even if there is a more extended interval before the second. However, you will not be maximally immune during that period and therefore more vulnerable to infection.

If you were to get the vaccine too soon before the recommended interval, you might short-change yourself since you may not have given your immune system enough time to get primed The idea is that the first shot helps your body recognize the virus and build a response and that once that response is maximized, the second shot further strengthens that response. So the general thinking is you can be too early but there are less concerns about being late. Ask your doctor for guidance if you need to follow a schedule outside of the manufacturer's recommendations.

Can I mix and match?

It’s not recommended. Mixing and matching is one of those actions that will inevitably occur but for which science currently lacks data. For now, I recommend you mix and match your Brown with a Burgundy and not your Moderna with a Pfizer.