Yes, the Pfizer/BioNTech and Moderna Covid-19 vaccines have received emergency use authorizations (EUAs) from the U.S. Food and Drug Administration (FDA). Yes, that’s exciting news. Yes, the initial Phase 3 clinical trial results to date suggest that both vaccines are reasonably safe and effective.
But that doesn’t mean that the general public and scientific communities should stop asking questions about the vaccines. The vaccines are still very new and different from previous vaccines, and a number of unknowns still remain.
Remember emergency use authorization is not the same as full approval. As anyone who has waddled quickly to the bathroom muttering, “OMG, OMG, not now, not now,” things can be very different during an emergency. An emergency forces you to use different criteria to determine what to do. For example, a bathroom emergency may make you tell your date, “look, I can’t listen to your heartbreaking story about missing your big chance to be on that Progressive commercial, because something is moving inside me, and it’s not emotions,” when normally you’d sit through the story.
Similarly, the current Covid-19 coronavirus pandemic is an emergency, which means that action needs to be taken now. The lack of a coordinated national response has allowed the virus to spread throughout the U.S., resulting in over 330,000 deaths and counting, and left many banking on a Covid-19 vaccine to change the situation. One out of every 1,000 people who started 2020 in the U.S. has now died from Covid-19. Every day there are more and more deaths. A so-called “herd immunity” strategy of letting the virus run relatively unchecked through the population would be about as effective as using a vacuum cleaner plunger to try to remove something lodged between your teeth. So the risk of you getting Covid-19 and potentially suffering bad outcomes is real.
Given this backdrop, a EUA means that the FDA has determined that the currently understood benefits of the Pfizer/BioNTech and Moderna Covid-19 vaccines outweigh the currently understood unknowns of the vaccines and the risks of getting Covid-19. A EUA occurs when “there are no adequate, approved, and available alternatives,” in the words of the FDA website. It does not mean that the Covid-19 vaccines are completely risk-free. The EUA does not mean that the two Covid-19 vaccines would be necessarily available for use at this stage if conditions were different in the U.S. Therefore, don’t treat the available Covid-19 vaccines exactly the same as you would more established vaccines that have been fully approved, on the market, and studied for years such as the measles-mumps-rubella vaccines and the seasonal flu vaccines.
Of course, this does not mean that you shouldn’t get the currently available Covid-19 vaccines. This does not mean that the currently available Covid-19 vaccines are not reasonably safe and effective. However, while the Pfizer/BioNTech and Moderna Covid-19 vaccines are being rolled out, it is important to manage expectations and keep seeking the answers to the following eight unanswered questions:
1. What duration of protection does each vaccine offer?
You can’t hurry love and you can’t hurry time. The Pfizer/BioNTech and Moderna Phase 3 clinical trials only began this past July. And it’s not as if over 30,000 study participants showed up immediately for each trial once the two trials got started. That would have resulted in ridiculously long lines. Instead, it took some time for each of the trials to enroll their participants. That means that study participants have been followed for at most five months so far. So no one can tell for sure how long immunity may last after vaccination. The answer to this question will likely emerge later in 2021 when enough time has elapsed after vaccination.
2. What is the true effectiveness of each vaccine?
Circumstances matter. Your rendition of “My Heart Will Go On” from the movie Titanic may sound great in the shower by yourself with only your soap, your loofah, and your One Direction shower paraphernalia. But how about in front of a real audience? Suddenly, “you’re here, there’s nothing I fear,” may sound more like “your beer, there’s nothing I beer,” uttered by someone re-living puberty. Similarly, what happens in a clinical trial doesn’t necessarily apply completely in the “real world.” Real life can be a lot messier.
That’s why vaccine effectiveness is not exactly the same as vaccine efficacy. Vaccine efficacy is what’s measured in clinical trials. By contrast, vaccine effectiveness is what’s measured in real world settings. Both are equal to the percentage of unvaccinated people who ended up getting a Covid-19 coronavirus infection minus the percentage of vaccinated people who ended getting a Covid-19 infection divided by the percentage of unvaccinated people who ended up getting a Covid-19 coronavirus infection. So if in a clinical trial, 1 percent of the unvaccinated people and 0.1 percent ended up getting a Covid-19 coronavirus infection then the vaccine efficacy is:
(0.01-0.001)/0.01 = 0.90 or 90%
Vaccine effectiveness tends to be lower than vaccine efficacy because things are less than ideal in the real world. Your vaccines may not be handled as carefully as they were in the clinical trial. You may not follow instructions and Covid-19 precautions as carefully as those who have been enrolled in the clinical trials. After all, people who choose to enroll in a Covid-19 Phase 3 clinical trial may not be your typical people. They probably aren’t the types that will take Covid-19 risks such as jumping into maskless mosh pits.
Plus, remember that the Phase 3 trials started during the Summer months when transmission of the virus may have been lower. It remains to be seen how effective the vaccine may be in preventing infection during the Winter months, the hazy shade of Winter, when Covid-19 coronavirus transmission seems to be higher, as I described previously for Forbes. The effectiveness of any thing depends on the risk. A kilt may be quite effective at covering yourself up when you are sitting down but not when you are on a trampoline. In the same way, the effectiveness of a vaccine depends on how widespread the virus may be.
3. Does the vaccine prevent you from being infected with the virus?
So far, the published data does not seem to really answer this question. For example, a December 10 publication in the New England Journal of Medicine described how investigators measured the efficacy of the Pfizer/BioNTech vaccine in the Phase 3 clinical trial so far. They determined how well the vaccine seemed to prevent “confirmed Covid-19,” which was defined as “the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting,” along with a respiratory specimen positive for SARS-CoV-2. The study also measured the vaccine’s efficacy in preventing severe Covid-19.
This is not the same as measuring how well the vaccine may have prevented infection with the Covid-19 coronavirus in the first place. As has been demonstrated, many people can become infected yet have either very mild or no symptoms. While a vaccine preventing more severe Covid-19 is certainly very useful, such a vaccine won’t be as effective at stopping the spread of the Covid-19 coronavirus as one that could prevent infection, which brings us to the next question.
4. Can you still spread the virus if you are vaccinated?
The answer is definitely maybe. First of all, the measured vaccine efficacy to date is very high but is not 100%. Therefore, there is still a chance, albeit potentially a small one, of getting Covid-19 and having more severe disease after getting vaccinated, especially with the virus spreading widely. Secondly, again, not getting Covid-19 with symptoms is not the same as not being infected with the virus. The question is how often does the vaccine prevent you from getting infected and shedding the virus. As we know, there have been plenty of asymptomatic Covid-19 coronavirus infections before the vaccines’ arrival. Even if you have no symptoms, you can still carry and spread the virus to others. Can this still happen if you are vaccinated? The jury is still out, and they’re getting vaccinated. To determine how well the vaccines prevent such spread, investigators would have to regularly test study participants for the presence of Covid-19 coronavirus and then determine how much SARS-CoV2 they may be shedding.
5. How might the vaccine perform for people with different risk factors such as different levels of being immunocompromised?
Although each of the clinical trials has enrolled over 30,000 study participants to date, the trials are still limited samples of people. The sheer number of study participants doesn’t necessarily mean that the sample has enough diversity for the results to apply to everyone. For example, if you were to use the 80,000 or so people who attended a given pre-pandemic Green Bay Packers game as a sample, you might conclude that wearing cheese on your head is quite common. Similarly, just because the Covid-19 vaccine has a certain level of safety and efficacy among the clinical trial participants, doesn’t mean that the same levels will be seen in people who have different medical conditions and are taking different medications. More studies are necessary to delve deeper. For example, separate studies may focus on giving the vaccines to those who have weaker immune systems for various reasons.
6. Will the vaccines protect against Covid-19 coronavirus variants such as the ones from the United Kingdom and South Africa?
Meghan Trainor may have said that it’s all about the bass. But in this case, it’s all about the spike, the spike protein, that is. The Covid-19 coronavirus looks like a little spiky massage ball, covered in tiny spikes made out of protein. The spikes help the virus enter your cells like a crow bar can help you pry open a safe full of sushi. Both the Pfizer/BioNTech and the Moderna vaccines contain mRNA that code for this spike protein. This mRNA is essentially a blueprint for the spike protein. Once the mRNA gets into your body and is gobbled up by your immune system cells, those cells use the mRNA as recipes to make the spike protein. Your immune system sees this unusual spike protein, effectively says, “what the bleep is that,” and then builds up a defensive response.
Alter the spike protein enough and the vaccine may no longer be as effective at protecting against the virus. Right now, it’s still not completely clear whether the mutations present in the Covid-19 coronavirus variants found in the United Kingdom, South Africa, and Nigeria may affect vaccine effectiveness in any way. At present, the mutations haven’t seemed to alter the spike protein to the point that the virus can escape the protection offered by the vaccine. But more studies are needed to say for sure.
7. What are all the possible side effects of the vaccines?
The Britney Spears line, “I’m not that innocent,” can apply to basically everything in life. Nothing is completely safe. Everything has risks. Even the Baby Shark song can be dangerous should hearing, “Baby shark, doo, doo, doo, doo, doo, doo,” over and over again make you repeatedly hit your forehead with your shoe.
Therefore, safety is relative. Everything you use on a daily basis whether it’s a plunger, a BTS Pez dispenser, or a bowl of ziti brings possible risks. But you choose to use each item because the benefits far outweigh the risks. The FDA has determined that the potential benefits of the Pfizer/BioNTech and Moderna Covid-19 vaccines outweigh the risks. The benefits of preventing Covid-19, a potentially life-threatening infection, should be clear. So far, the clinical trials have not revealed an unacceptable level of serious side effects. Sure, there have been some issues such as allergic reactions and cases of facial weakness or paralysis (i.e., Bell’s palsy) as Nina Shapiro described for Forbes. But to date, no more serious problems have emerged.
That being said. The mRNA technology used for Pfizer/BioNTech and Moderna vaccines is still quite new. It’s been tested in other animals but until this year hasn’t really been tested in humans. As you know, you are not the same as a Rhesus macaque. You don’t expose your genitals when you are frightened. At least, you shouldn’t. You also don’t paint things with your feces, most of the time. Similarly, your body may not be exactly the same as a macaque’s.
Nonetheless, when side effects occur from a vaccine, a medication, a food, a plunger to your head, or anything that goes on or in your body once or twice, they tend to occur fairly soon afterwards. It’s not common for you to wake up one day and say, “whoa, I am really feeling the effects of that hot dog extravaganza that happened five years ago.” So there is a decent chance that the ongoing clinical trials have already picked up a bulk of the side effects that may occur from the two Covid-19 vaccines. A vaccine that you get once or twice is not the same as something you take or eat nearly every day.
Regardless, continue to follow the Covid-19 vaccine studies that are being done. Since an EUA is not the same as approval, the FDA will keep monitoring the ongoing clinical trials as well as the vaccine roll-out. It will be important to maintain a vaccine surveillance system that tracks any side effects that occur on an ongoing basis.
8. How might the vaccine work in children and pregnant or breastfeeding women?
You may believe the children are our future and that you should teach them well and let them lead the way. Nevertheless, they haven’t been part of the initial Phase 3 clinical trials. That’s why the Pfizer/BioNTech vaccine received an EUA specifically for those 16 years and older and the Moderna vaccine for those 18 years and older. It’s not as if reaching an age where you ride a moped, fly a glider, or legally change your name to Tablecloth should affect the should affect how the vaccine works. Chances are the vaccine will work similarly in those who are a little younger than 16 years old. Moderna has already begun a clinical trial for 12 to 17 year olds, as Mary Markos and Jeff Saperstone reported for NBC Boston. Even younger kids may not be the same though. As anyone who has gone through middle school knows, bodies, ahem, change during puberty. More studies will be necessary before lowering the age limit for vaccination.
The Phase 3 clinical trials didn’t really include women who are pregnant or breastfeeding either. As this CNBC video shows, Vice-President Mike Pence was asked if he fell into either category before receiving the Covid-19 vaccine:
According to a Practice Advisory from the American College of Obstetricians and Gynecologists (ACOG), “Covid-19 vaccines should not be withheld from pregnant individuals who meet criteria for vaccination” and “should be offered to lactating individuals similar to non-lactating individuals when they meet criteria for receipt of the vaccine based on prioritization groups.” The Advisory also states that “pregnancy testing should not be a requirement prior to receiving any EUA-approved Covid-19 vaccine,” and emphasizes that the mRNA in the vaccines “do not enter the nucleus and do not alter human DNA in vaccine recipients. As a result, mRNA vaccines cannot cause any genetic changes.” Ultimately, it is a good idea to talk to your doctor if you are pregnant or breastfeeding before deciding whether to get the Covid-19 vaccine.
Again, all of this doesn’t mean that you shouldn’t get the Covid-19 vaccine. Just don’t approach vaccination and the pandemic like the title of that Tom Cruise and Nicole Kidman movie Eyes Wide Shut. Understand that the Covid-19 vaccines are still relatively new technologies with accompanying unknowns. Continue to follow the Covid-19 vaccine trials and any emerging studies and data. Keep in mind that while the vaccines are a significant advance, you’ll still have to take precautions like social distancing and wearing face masks for now even after getting vaccinated.
At the same time, realize that not getting the vaccine brings risk as well, especially if you are a front-line healthcare professional or someone who is at higher risk for bad Covid-19 outcomes. With the Covid-19 coronavirus so widespread and basically uncontrolled in the U.S., the risk of getting Covid-19 and suffering bad consequences is real. Remember that the Covid-19 coronavirus pandemic is a public health emergency. And things are a bit different during an emergency.