All your COVID vaccine questions....

A few disclaimers

1. This document is fluid. I will continue to update as new questions and new data arise.

2. While blogs aren't always a trustworthy source, I hope that you'll consider my expertise. I have a PhD in immunology and I study the immune system in obesity and diabetes at an academic research institution funded by the AHA and the NIH/VA. I drive a 2003 Honda Civic. Thus I am not a shill for Big Pharma, I haven't made a name for myself professionally being pro- or anti-vax, and I'm not here to sell you any alternatives! I will continue to add citations and I am constantly listening to those with more expertise and experience in vaccine development, virology, public health, and medicine. Will link to some of their social media pages at the end. And you can read more on trustworthy sources here.

3. I am not here to convince you to get a vaccine for COVID today, in fact many of us won't have access to a vaccine until late spring or summer, however I do want to provide you with a resource that answers all of those burning questions you have today and makes you a little more comfortable with our knowledge of the vaccine!

What are vaccines?

You can think of vaccines as an immune system bootcamp preparing your immune system to fight an infection. You can also think of vaccines as a wanted poster hung up on the local pub windows. A vaccine teaches or trains your immune system to respond to a specific bacteria or virus so that if you are ever infected by that bacteria or virus, you can quickly and strongly respond with an appropriate response. Basically we take advantage of a system that you already have in place to develop adaptive immune memory.

Why should we get a vaccine that’s only 94% effective for a disease that 99% of people survive?

Contracting COVID, the known risks are death (fatality rate 1.5-2%), severe illness (14%), critical illness (5%), and many have long term symptoms (see “long haul COVID”), even if you’re young and healthy. And even with a .5% death risk and 330 million people in the US, that’s 1.65 million deaths assuming hospitals do not get overwhelmed. We’ve seen hospitals reach their maximum in the spring and now again in the winter, and this increases the risk of death from COVID when appropriate treatments cannot be administered, and increases the risk of death from accidents, heart attacks, etc, as there isn’t anyone who can treat you when you come into the ER.

Now the 94% efficacy rate is something different. This data from our phase III clinical trials (Moderna, Pfizer) suggests that the vaccines reduce the risk of getting symptomatic COVID by 95%, and the vaccines reduce severe COVID and death. So this question is comparing a 1% risk of death with the infection to a 5% risk of even getting the infection with noticeable symptoms. Current research will help determine if the vaccine can also prevent asymptomatic COVID.

What’s an mRNA vaccine?

mRNA vaccines contain the code for the spike protein that is on the surface of SARS-CoV2, binds to ACE2 receptors on human cells, and helps the virus enter human cells. This technology allows us to take advantage of your own machinery to produce the spike protein for you to mount a response to. Once inside your cell, the mRNA will be translated to protein and your cells will show it to the immune system. At this time, your immune system will recognize that it’s not a normal human protein and begin to mount an immune response. One major benefit to mRNA vaccines is that they can be quickly produced without growing a large amount of infectious material and we could potentially target more than one disease at time. Successful SARS-CoV2 vaccines will pave the way for many more in the future.

Can I get COVID from the vaccine?

The top contender vaccines with safety and efficacy data in human trials are currently mRNA vaccines or adenovirus vaccines. Both deliver genetic material messages for the spike protein on SARS-Cov2, but do not contain the full virus or full viral messages so they cannot infect or replicate as a full virus would.

What ingredients does this vaccine contain?

Moderna’s mRNA-1273 is made of RNA packed into lipid nanoparticles (think envelopes). The ingredients include 4 lipids (phospholipids and cholesterol to form the envelope) and the mRNA sequence in a Tris buffer (to stabilize the pH at 7.5) with sucrose (a sugar to help stabilize the vaccine) and sodium acetate (a salt to normalize the salinity). The Pfizer vaccine also contains similar ingredients.

Are the vaccines tested against a placebo?

Yes! The placebo is saline in both trials (salt water). In both trials, half the participants receive the placebo.

Have these vaccines been rushed?

These vaccines have been made in record time due to collaboration (the SARS-CoV2 sequence was shared in January), a ton of manpower (many scientists have dropped their normal work to study COVID-19), and a ton of funding (from govts, grants, gifts, and internal priority shifts). The federal government also allowed for the stacking of clinical trials, which cut down on total amount of time between then, but did not cut down on the time or objectives within the trials. Additionally, the vaccines were built off a ton of previous work on coronaviruses (search prior to 2019) and mRNA vaccines. mRNA vaccines were theorized in the 90s and have been in clinical trials since at least 2015. Not to mention we’ve had scientists devote their careers to studying coronaviruses (example1, example 2) and developing antibody treatments and vaccines for diseases like SARS and MERS(example1, example2). Additionally, with the pandemic currently occurring, we have many participants willing to participate in clinical trials with a decent likelihood of natural exposure (since we cannot ethically infect people with COVID to test the vaccine). Scientific enterprise has been building up to this moment for awhile now and we’ve been able to step up to the plate!

For more, here’s a great podcast with Dr. Kizzmekia Corbett, part of the Moderna vaccine development team at the NIH.

Is this vaccine safe?

Phase I and II clinical trials test safety and if participants develop an immune response to the vaccine. Phase III studies test if the vaccine is effective against the virus while continuing to testing safety in many more patients. Phases were stacked, for example we were doing efficacy testing in primates at the same times as phase I safety testing in humans to speed research productivity, but no phases were skipped or shortened.

Patients were enrolled in phase I trials in March (Moderna Phase I start date March 16, 2020, Moderna Phase I published data, Pfizer Phase I study start data April 29,2020) so we already have ~8 months of safety data and will likely have close to a year of data before a vaccine can be widely distributed. Other mRNA vaccines have also been in phase I trials since at least 2015, and we have not seen adverse effects from those vaccines. Additionally, the phase III trials included not only healthy participants, but they also included both elderly individuals and those at increased risk for severe COVID-19, including participants with diabetes, severe obesity and cardiac disease (Moderna, Pfizer).

There have been no major adverse effects reported in any of the Moderna or Pfizer vaccine trials (~40,000 vaccine participants total). The only severe symptoms reported from the Pfizer trial were fatigue in 3.8% of participants and headache in 2.0% of the participants. From the Moderna trial, no serious safety concerns were identified by the Company, and the most common side effects included pain at the injection site, fatigue, muscle soreness, headache, and swelling/ redness at the injection site

Safety will continue to be tracked for 2 years in all studies, and phase IV trials may track longer. Additionally, every vaccine batch is tested for potency, purity, and sterility and we have many systems to record and evaluate safety data and concerns following distribution (VAERS, VSD, CISA + more).

Now you really wanna know about long term effects at 5 and 10 years, but we don’t require that from clinical trials for approval. Adverse effects usually occur very shortly after receiving a vaccine based on the decades of data we have on vaccinations. And the risk of not administering the vaccine in order to test more is guaranteed death and illness. More on this in the next section.

Remember, vaccines are actually really safe. While the risk for specific events are different for each vaccine, on average, there’s a ~1/million risk of any adverse effects overall (there’s a 1/1 million risk of anaphylaxis, there are 1-2 additional cases of Guillain-Barre Disease for every million doses of flu vaccine administered, and ~1 individual has been compensated per million doses administered)

Contracting COVID, the known risks are death (fatality rate 1.5-2%), severe illness (14%), critical illness (5%), and many have long term symptoms (see “long haul COVID”), even if you’re young and healthy. And even with a .5% death risk and 330 million people in the US, that’s 1.65 million deaths assuming hospitals do not get overwhelmed.

Vaccines are not zero risk, but their potential risk is very low risk when you compare to the risks of becoming infected and developing disease.

What about the news reports of allergic disease or the Pfizer report of Bell's Palsy?

Remember, anaphylaxis is a common response to most vaccines, though the prevalence is about 1-2 in a million and it’s usually in response to ingredients in the vaccines. These only have lipids, a sugar, salts, and a buffer in addition to the mRNA though so previous reactions to a vaccine don’t guarantee a reaction here. It’s also not likely that those overlap with food or environmental allergens. However for anyone that have severe allergic reactions, consulting your medical provider would always be recommended. Moreover, PEG is one of the lipids is in a lot of food products including things like ice cream so people are hypothesizing that could play a role here (though the symptoms were also similar to syncope so still unsure of the nature of the reaction). There are a few noted cases of PEG allergy, but it’s just a few out of our whole population. Also when we consume foods, we can develop IgG antibodies to them, but the presence of these antibodies usually corresponds to tolerance, not reactivity, which is why IgG tests for food allergy are not worthwhile. And even IgE antibodies alone don’t classify someone as allergic without symptoms, so if you see any reports of PEG allergies or PEG antibodies in the population, don’t be alarmed.

Regarding the 4 Pfizer participants who developed Bell's Palsy, about 23/ 100,000 humans get the disease a year, so 4/ 18,000 isn't at a higher prevalence than could naturally occur. The company, government agencies, and advisory boards will continue to monitor for future reactions, but thus far there is no reason to be concerned.

Could there be long term effects?

It’s highly unlikely. Known vaccine related injuries occur within hours to weeks of vaccination administration, not decades down the road, because vaccine material is quickly taken up by the immune system and any “waste” is excreted from the body via normal processes. This is in contrast to medications that are much more likely to have long term effects because they may act on proteins or receptors in more than one organ of the body and you often take medications more than one time. That being said, we do continue to monitor vaccine safety by many surveillance methods even after they’ve been approved. Studies of these systems suggest that vaccines are remarkably safe and that the surveillance programs identified a large proportion of (usually insignificant) safety issues.

Could this vaccine cause autoimmune disease?

Not that we know of. Autoimmune diseases occur when the body reacts to itself, and while there are instances when infections can trigger autoimmunity, no studies to date have consistently shown vaccines as a cause of autoimmune disease. Even for the influenza vaccine that appears to cause Guillain-Barre Syndrome at a rate of one case per million vaccine recipients, the data should be viewed in light of the fact that natural influenza infection causes GBS at a 17x higher rate, and thus it is likely the specific influenza material and not the vaccine. That being said, safety is a primary goal of all vaccines, and we take clinical trials seriously and have multiple mechanisms to continue to monitor side effects at the population level once vaccines are approved (VAERS, VSD, CISA + more).

Could mRNA vaccines alter our DNA?

Nope! One of our major biological theories (on par with the theory of gravity) is called the central dogma. This says that our genetic code is stored in DNA in the nucleus, transcribed to RNA as a short term message that can leave the nucleus, and be translated into protein in the cytoplasm. Humans don’t have any built in mechanism to get RNA back into the nucleus or to turn RNA into DNA, and we have no scientific evidence that this can occur with mRNA vaccines. Remember they’ve been studied since the 90’s!

Is it safe for the Black community?

I recognize that vaccine hesitancy in the Black community goes beyond misinformation by celebrities and internet bloggers. There is substantial history of misconduct by the medical community including but not limited to the Tuskegee Syphilis Experiment, Sim's gynecological experimentation on enslaved Black women, the use of Henrietta Lack’s cells without consent or compensation, and ongoing disparities in medical outcomes. We will not earn this trust back overnight, and maybe not even in our lifetime, but we can do much better. Widespread recognition and understanding of this history is an important step. Moreover, supporting Black physicians and scientists can help to integrate and create inclusion in our spaces, research and patient care initiatives should aim to reduce current health disparities, and better community outreach may help to create a bridge between communities and the medical system.

Regarding the COVID vaccine, effort was made to include Black participants in the clinical trials. From the Pfizer phase III trial, approximately 10% of Pfizer study participants were Black, and from the Moderna phase III trial, 11,000 participants were from communities of color (37% of the study population), which included more than 3,000 participants who identify as Black or African American. Moreover, there are many incredible Black researchers involved in COVID research and vaccine development, including Dr.s Kizzmekia Corbett and Cherrelle Dacon at the NIH, Dr. Donald Alcendor at Meharry Medical Center/ Vanderbilt University, and many rising graduate students and research technicians around the country, and there have been Black physicians and scientists involved in science communication, including but not limited to Dr.s Uche Blackstock, Lachelle Dawn,Theresa Chapple, Juliet Morrison, Keke Fairfax, Darian Sutton, and Akilah Jefferson Shah. I’d highly recommend seeking out their work for more information.

For a few great links now- see "COVID-19 with Dr. Corbett PhD" at ~23 min, this conversation with Dr. Blackstock, this news segment with Dr. Blackstock, and this conversation with Dr. Fauci.

But what about the side effects like fatigue, soreness, and fever with the vaccine?

This is a good place to point out the difference between mild to moderate side effects like fatigue, soreness, redness or swelling at the injection site, and a fever that may occur with 24-48 hrs of getting the vaccine with severe side effects (adverse effects/ vaccine injuries) like anaphylaxis. The first mild- moderate effects are due to an immune response and suggest you’re responding to the vaccine. Note that if you do not have symptoms, that does not mean you’re not responding to the vaccine. Our immune systems all respond slightly different. Additionally, we should note that many people equate these symptoms to getting the disease from the vaccine, and that’s also not accurate.

While adverse effects and vaccine injuries are rare, they do occur as they do with any medication. If you develop illness or abnormal symptoms following vaccination, you or your doctor should report them to the Vaccine Adverse Effect Reporting System (VAERS). In the very rare event that a vaccine causes a serious problem, the National Vaccine Injury Compensation Program (VICP) may offer financial help. Vaccination risks, common side effects, and information about reporting to VAERS and filing through the VICP can both be found on vaccine information statements that should be provided to you when administered, like the one shown here. For additional information, here is a list of “common” injuries filed through the VICP.

If the vaccines are safe, why are vaccine manufacturers exempt from liability?

For vaccine related injuries, the government agreed back in the 1980’s to pay for injuries in order to incentivize companies to make and distribute vaccines because we realized how important they are for public health. Remember everything comes with a small risk, even Tylenol and vitamins, yet billions of people take vaccines that the monetary risk for companies is higher than for other drugs. Here’s a good article by a fantastic science writer, James Hamblin at the Atlantic, that further discusses this process.

The vaccines have to be frozen for travel and storage. Will they be injected cold?

mRNA is notoriously unstable. It’s a short term message- think a snap chat or Instagram story- that tells your body which proteins to make immediately and is then quickly degraded so that your body can continue to respond to its environment and make proteins as needed. Therefore, the mRNA vaccines will be stored and shipped very cold. However, they’ll be thawed prior to injection and then will be available for translation for ~24 hrs or so.

Does the vaccine contain microchips?

Nope. Not even sure what to cite here. Just nope and nope.

Do the vaccines contain aborted fetal tissue?

The Pfizer and Moderna COVID vaccines (+NovaVax and Sanofi) use no fetal cells during any point in manufacturing. If you are ethically opposed to their use no worries! Opt for one of those options once available. Also none of the vaccines in clinical trials use the MRC-5 line.

What: Fetal embryonic cells are used as mini factories to produce the huge quantity of viruses and viral vectors needed for some vaccines. They were obtained from pregnancy terminations decades ago. The cells have since replicated in culture, so the descendant cells are not the same exact cells from the terminated pregnancy.

Why: To create more virus, we need a host that allows the virus to divide many times. Most cells only divide 50 or so times, but because fetal cells have not divided many times, they can be used much longer. Human viruses tend to grow better in cells from humans than animals because they infect humans- and using human cells reduces the likelihood of introducing a second unwanted virus that’s harbored in animal species.

How: We have been growing these cells for decades and can keep small quantities frozen to maintain our stocks. This ensures that no further sources of fetal cells are needed to make these cell lines or vaccines.

By the time the vaccines get to you, there is very little associated fetal tissue or DNA. The cells are killed because the new viruses often burst the cells open, and cellular components and DNA are broken down in the processing. We go through additional steps to purify the virus/ viral vectors, though this isn’t 100%.

Thus any mention of cell culture or DNA materials on the ingredients list is due to complete transparency- like warning you that a candy bar is made in a factory with peanuts. In the worst case, there is a faint trace of peanut residue, though it’s highly likely there’s very little to none.

And new vaccine technologies side step the need for using cell factories at all! Production of mRNA vaccines is actually easier and quicker because it doesn’t need to use cell culture. Cheers to everyone who’s worked hard for the past decade on this technology!

Is it possible that the vaccine can cause sterilization or infertility?

We have no mechanism or evidence for this currently. The claim circling internet spheres *without evidence* is that syncytin-1 is a protein involved in placental development that is similar enough in sequence to the spike protein in the vaccines that you'll have cross reactivity. However, the sequences really aren't that similar (no sequence similarity on BLAST- a genetics alignment tool that helps compare genetic sequences) and antibodies recognize regions on folded proteins, so sequence alone wouldn't determine cross reactivity. @virus.vs.labcoat breaks this down even better on her Instagram stories. Moreover, the placenta is formed from the fetus and thus wouldn't have direct access to mother's blood supply and antibodies until at least partly formed (which I honestly didn't know til this week and my friends, that's SO interesting!). And COVID infection isn't associated with first trimester loss. If our antibody response to the vaccine showed cross reactivity, we would have the same reactivity with natural infection.

And in fact, 12 people in the Pfizer trial who received the vaccine became pregnant naturally as of November 14, 2020 and 6 people in the Moderna trial who received the vaccine became pregnant naturally as of Dec 2, 2020. Note: and that was even being told to try not to get pregnant while enrolled.

Is the vaccine safe for pregnant or breastfeeding people?

Short answer: likely, but we don’t have data on this yet. Pfizer is currently completing animal testing on pregnancy and will begin clinical trials in pregnant people soon. The Society for Maternal and Fetal Medicine did release a statement advocating for pregnant people to be in clinical trials and suggesting that the vaccine be available to pregnant people for them and their physicians to assess risk on. Please consult your own physician to weigh the risks and benefits when you're eligible for the vaccine and see these great summaries from two great OBs for more!

https://www.youtube.com/watch?v=smsmsM1RbIg&t=7s

https://www.youtube.com/watch?v=xTQ3cf81KUs

Is the vaccine safe for children?

Short answer: likely, but we don’t have data on this yet. Children 12 and up are currently being included in clinical trials now that we have general safety data for adults, and those under 16 will not have FDA approval for the vaccine until we have more trial data.

Answers coming soon:

Should we get the vaccine if we’ve already had COVID?

Likely: awaiting ACIP and CDC recommendations.

Where can we go for more information?:

**Note that I'm directing you to a lot of different individual experts and a lot of different government/ healthcare/ sources that all say really similar things that align with the data we have and therefore the scientific consensus. These entities are all paid differently, report to different people, and have different goals. The government and healthcare agencies are often very reputable, even with the recent politicization of so many COVID things. What was published was often still mostly accurate. And note that these individuals aren’t selling their own supplement lines in lieu of medications (conflict of interest) and all have relevant experience and training. If you google them, they're also free from cases of scientific misconduct, have not had their licenses revoked, and are not part of paid political campaigns

https://www.chop.edu/centers-programs/vaccine-education-center

https://www.cdc.gov/vaccines/index.html

https://www.immunize.org/handouts/

https://www.mayoclinichealthsystem.org/topics/immunizations

https://www.fda.gov/vaccines-blood-biologics/vaccines

Experts with relevant education and experience on Twitter: @virusesimmunity (viral immunologist),@angie_rasmussen (virologist), @epiellie (epidemiologist), @nataliexdean (bio statistics, infectious disease, and vaccine studies), @erictopol (physician-scientist), @ucheblackstock (physician and health equity advocate), @florian_krammer (virologist),

Experts with relevant education and experience on Instagram: @kinggutterbaby (infectious disease researcher), @jessicamalatyrivera (infectious disease epidemiologist), @jesseosheamd (infectious disease physician), @kizzyphd (vaccine development at NIH), @virus.vs.labcoat (virologist), @science.sam (neurologist and incredible science communicator), @dr.martaperez (OB-Gyn), @doctor.darien (physician)

Great article on the immune system and COVID: Ed Yong, The Atlantic

Podcasts: Unbiased Science (Episodes 12-14 vaccines, others on COVID), Speaking of Science (Episode 14 with Dr. Kizzmekia Corbett on mRNA vaccine development), Peds Doc Talk (Episodes 31 and 32 on vaccinating children)

Webinars: Mark Denison from Vanderbilt University, Kizzmekia Corbett from the NIH vaccine team