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Frequently asked questions about COVID vaccines



I get a lot of questions about the COVID vaccines from Pfizer and Moderna currently available in the US. People are understandably wary of vaccines that are the first of their kind and produced in record time. In an effort to help get more good information out there (and hopefully alleviate some anxieties), I decided to compile a FAQ document covering a wide range of vaccine-related topics. Roughly, these are ordered by how frequently the question is asked, though I didn’t actually keep a tally…


What’s different about mRNA vaccines?

Traditional vaccines used either live, attenuated virus or viral protein extracts to provoke an immune response. mRNA vaccines accomplish the same thing by inducing your own cells to make viral protein (in this case, the spike protein on the surface of SARS-CoV-2). This technology has two key advantages. First, itincreases immune exposure to the viral protein because mRNA is not degraded as quickly as an attenuated virus or protein-adjuvant combination. Second, and perhaps more importantly, novel vaccines can be created much faster using mRNA technology. Rather than genetically modifying a virus and trying to keep it viable in perpetual culture or extracting proteins and developing an appropriate adjuvant, the desired mRNA sequence can be entered into a computer and “printed” using automated platforms to combine base-pairs.


Should we be concerned that vaccine developers were allowed to forego animal testing?

It’s true that animal testing was effectively bypassed in producing COVID vaccines. We’ve known for years that animal models really aren’t great predictors of how well a vaccine or drug will perform in humans, but we’ve kept doing it anyway - largely as an additional safety checkpoint. Frankly, it’s not so much an issue of “let’s see how well this vaccine works in a mouse,” but rather being able to say “look, human volunteers – the mice who got this vaccine didn’t have anything terrible happen to them!” At this point, however, we have 140 years’ worth of experience with vaccines, and we’ve gotten pretty good at identifying elements that should be safe in humans. In the case of COVID, we just didn’t have the time to spare to complete animal trials.


Historically, the full process of vaccine development with all the usual animal studies and regulatory checkpoints could take up to 20 years. The previous time record for developing a vaccine from start to finish was 4 years for the mumps vaccine. I expect we will be able to shorten vaccine development substantially in the future using what we’ve learned during the pandemic and still produce safe, effective vaccines. Despite the incredible turnaround time for these new vaccines, I think they have been as well-studied as they could be in the time available, and I do not hesitate to recommend them.


How long does the mRNA strand from the vaccine stay active within our cells?

I’m not aware of any data on persistence of mRNA in the COVID vaccine, specifically, but we know that naturally-produced mRNA fragments in mammals can stay active anywhere from several minutes to several days. This is significantly shorter than the lifespan of most mammalian cells, and the expectation is that the intracellular enzymes that degrade our own innate mRNA will degrade vaccine mRNA in a similar timeframe.


Is there any risk of the mRNA vaccines “rewriting” our DNA?

No - mRNA is a normal product of DNA transcription, and we have billions of these code fragments in our bodies at any given time. Transcription from DNA to mRNA is a one-way process – mRNA strands are incapable of entering the cell nucleus and rewriting our base DNA code. It’s somewhat analogous to running a software program, which doesn’t change the underlying code. Using mRNA in a vaccine simply introduces a specific set of protein-making instructions to existing cellular machinery. mRNA segments from the vaccine are naturally degraded once their instructions have been read and executed.


How well do the Pfizer and Moderna (mRNA) vaccines work?

Pfizer reports 95% efficacy with Moderna’s vaccine effectively equivalent at 94.5% for the time period studied in the Phase 3 trial (up to 5 months). Note that both of these figures only apply to people who receive both doses of the vaccine series (each vaccine requires 2 doses at least 21 days apart). While no one is currently recommending stopping vaccination after one injection, Pfizer estimates that a single dose may be 82% effective. Moderna estimates 63% efficacy for a single dose of their vaccine.


Are there patients the mRNA vaccine would not work in – for example, those who are immunosuppressed or those with an autoimmune condition?

There is no reason to think that mRNA vaccines would be wholly ineffective in any particular population. For those with altered or suppressed immunity, I would predict that the degree of immune response to the vaccine (i.e. antibody titer) would be lower, but that doesn’t mean the vaccine wouldn’t be protective. Ultimately, the mRNA vaccines produce the same end result as previous vaccines – presenting a viral protein to the immune system so it can learn to recognize that protein and produce an antibody response that can neutralize whole virus before it has a chance to invade cells.


I have heard that Pfizer will be unblinding their trial participants. Will this hamper our ability to study long term safety and efficacy?

It’s standard practice in trials where a vaccine proves effective to unblind the groups near the end of Phase 3 and offer the real vaccine to everyone who got placebo. It doesn’t affect our overall ability to study safety and efficacy, however, because we have the Vaccine Adverse Events Reporting System (VAERS) to track adverse outcomes following vaccination over the long term. Once a vaccine is out of clinical trials, unvaccinated people in the general population become the controls, and vaccine safety can be examined using cross-sectional population studies.


Are the vaccines safe in pregnancy?

Pregnant women were excluded from Phase 3 trials for both Pfizer and Moderna vaccines. To my knowledge, they have not been included in any ongoing COVID vaccine trials. Unfortunately, we go through this every time a new vaccine comes out because no one wants to expose pregnant women to potential harm unnecessarily, even though they will ultimately need to be vaccinated. In this case, CDC did not explicitly include pregnant women in their initial vaccine distribution plan. Nevertheless, this does not mean that these vaccines are unsafe in pregnancy. The Advisory Committee on Immunization Practices (ACIP) has taken the position that pregnancy should not be a reason to forego vaccination in high-risk groups like healthcare workers. Based on the mechanism of action, there is no reason to believe that these new vaccines pose a greater risk of adverse reactions when given to pregnant women. We do know, however, that pregnant women are at higher risk for severe disease if they get COVID-19. It’s hard for me to make a formal recommendation without much in the way of data to back it up, but if my wife were pregnant, I would advise her to get the vaccine.


Are these vaccines safe for nursing mothers?

While acknowledging that we don’t have data to back it up, I would say yes. Even if vaccine components are passed in breast milk (we don’t know for sure whether they are or not), it’s mostly just small strands of protein surrounded by lipid that would be broken down by an infant’s stomach acid. There’s no risk for infection because none of the current frontrunner vaccines contain SARS-CoV-2 virus.


Can immunocompromised people safely receive these vaccines?

Because they are not live virus vaccines, people with conditions that compromise their immune systems should not be at increased risk for adverse reactions. Once again, however, no immunocompromised patients have been included in any COVID vaccine trials to date. People in this category can expect to have a less robust response to COVID vaccines, but the vaccines are very unlikely to cause them direct harm. Public health entities are prioritizing people in this group for vaccination, although they are being advised to continue taking additional precautions like masking and social distancing due to their risk for inadequate antibody response to vaccination.


Should I get the vaccine if I already had COVID?

Yes – we have plenty of evidence that immunity from natural infection wanes over a period of months. Vaccine-induced immunity appears to be more robust and longer-lasting. Natural immunity is more likely to be lost due to viral mutations. So far, the mRNA vaccines appear to be effective even against mutated strains of SARS-CoV-2.


Will these vaccines work for mutated strains of SARS-CoV-2?

Highly likely – the mutation that has everyone worried about higher transmission rates (N501Y) does not significantly affect the overall shape of the spike protein. Pfizer has conducted experiments to show that antibodies from vaccinated people can still neutralize the mutated virus in vitro.


Am I being microchipped?

No – this rumor stems from discussions of “nanotechnology” in the new mRNA vaccines. Nanotechnology is the science of objects between 1 and 100 nanometers in size – not necessarily tiny computers or robots. In this case, “nanoparticles” have been employed in the form of tiny lipid droplets that protect mRNA until it can be taken into a cell.


Once vaccinated, will we still need to be screened for symptoms at work? If we have symptoms or a COVID-positive contact, will we still need to quarantine?

Yes and yes. Even though the vaccine is highly effective (95% efficacy), we can’t positively identify who falls into that 5% of people who don’t get protection from vaccination. Masking, distancing and symptom screening will continue for months to come, I’m afraid. If you get consistent symptoms after receiving the vaccine, I would encourage you to get tested for COVID. For now, quarantines will still be implemented for vaccinated close contacts of known positives where possible, though this has become difficult in the healthcare setting due to staffing shortfalls. I suspect this requirement will be relaxed as we get more healthcare workers vaccinated and continue to have a high load of COVID patients across the country.


What side effects have been reported with the vaccines?

The most commonly-reported side effects are similar to flu vaccines – redness, swelling and tenderness at the injection site. A small number of patients (< 5%) report short-lived flu-like symptoms, including chills, muscle aches, fatigue and headache. In the Pfizer trial, patients who developed systemic symptoms like this had them for a median period of only 1 day after vaccination. Some healthcare facilities have encouraged their employees to schedule vaccination on their days off or at the end of a workday when they’re off the next day to allow time for recovery. Keep in mind that no one had reactions severe enough to stop the trial, and the majority of systemic symptoms reported were mild to moderate. This table breaks it down nicely: https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fvaccines%2Fcovid-19%2Finfo-by-manufacturer%2Fpfizer%2Freactogenicity.html


I have heard that people with drug allergies should not take the vaccine. Is this true?

The warnings apply to people with a history of “significant” or “severe” allergic reactions – basically anaphylaxis or symptoms involving the airway like tongue swelling, wheezing or shortness of breath. Milder previous drug reactions like itching, rash or hives are unlikely to predict an allergic reaction to the COVID vaccine. The rates of significant allergic reactions observed with the vaccine are quite low – currently estimated to affect about 0.00001% of patients. Rates of reported drug allergy in the general population are much higher – about 10% report a penicillin allergy, for example. The warning really only applies to those whose reactions required emergency medical care like administration of epinephrine. This applies regardless of what provoked the allergy – a drug, food or environmental exposure.


Should we continue to wear masks after receiving the vaccine?

Yes – I think we will all be stuck with routine masking until we reach herd immunity. At best, this will be toward the end of 2021. As I mentioned previously, we don’t really have a way to identify the 5% of people who don’t get protection from the vaccine. There’s also the practical issue of not being able to tell quickly in public who has been vaccinated. Even if we give out “vaccine passports” to those who complete the series, it’s a lot easier for shops and restaurants to make everyone wear a mask instead of stopping everyone individually to check their vaccine documentation.


We know COVID-19 can cause neurologic symptoms in some patients. Are there any concerns for neurologic effects from the vaccines?

No severe neurologic reactions have been attributed to the vaccines studied to date. One case of transverse myelitis in the AztraZeneca trial was determined to be unrelated to the vaccine. Cases of COVID-19 encephalitis have been attributed either to viral invasion of brain tissue (which has been confirmed on autopsy) or an autoimmune-type reaction to viral infection. Because the COVID vaccines present the immune system with only a single antigen (the SARS-CoV-2 spike protein), rather than a whole virus, it’s much less likely to provoke an autoimmune reaction.


Will we need to get re-vaccinated? If so, how often?

We don’t know yet how durable immunity from the vaccine will be. The good news is that antibody titers dropped very little in months 2 and 3 in patients where those data points were collected. Antibodies from natural immunity drop off much faster, suggesting that vaccine-induced immunity to COVID will last longer than natural immunity following infection. Given what I know right now, I expect that these vaccines will be effective out to at least 6 months and probably closer to a year. That’s really all we need to halt transmission if we can get a majority of the population vaccinated quickly. It really depends on how things progress through 2021 – if we can reach herd immunity by the end of the year, there will be less urgency to re-vaccinate everyone, even if we find that immunity starts waning after 6 months or so.


Will COVID vaccination become mandatory?

Not any time soon, because we simply won’t have enough vaccine for everyone for months to come. I suspect it will eventually be required in the healthcare setting just like the flu vaccine, but I’m not aware of any specific plans for this right now. It remains to be seen whether it will make it on to the required list for school enrollment. I suspect not, since COVID-19 disproportionately affects adults in terms of symptomatic illness.


How much of the spike protein do the Pfizer and Moderna mRNA vaccines encode? What are the differences between the vaccines in terms of the mRNA sequence and lipid composition?

Both vaccines encode the entire SARS-CoV-2 spike protein. The specific sequences are proprietary and haven’t been made public yet, but the differences we know about are subtle. Some of the sequences near the end of the mRNA fragments provide instructions on how the protein should be folded. Moderna, for example, went with a sequence that keeps the spike protein in its prefusion state – in other words, the way the protein is folded on the surface of SARS-CoV-2 before it attaches to a human cell. The spike protein changes shape as it attaches to a cell wall, but we want the immune system to recognize it before that happens. I haven’t seen specific information on how Pfizer configured their spike protein code.


Both vaccines use proprietary lipid carriers to protect the mRNA strands during transport, so we don’t have details on what each carrier contains. The lipid solutions are similar enough to the lipid found in the surface of our cells that it allows the vaccine mRNA complex to cross the cell membrane, where it is transcribed in the cytoplasm.


How well do the Pfizer and Moderna vaccines work for preventing severe COVID?

Both vaccines look good for preventing severe disease. Moderna’s trial had zero patients with severe COVID in the group that received vaccine. Pfizer reported one severe case of COVID that occurred after the first vaccine but before the second, and another severe case that occurred after both vaccine doses were administered. On the surface, it might appear that Pfizer’s vaccine is less effective for preventing severe disease, but the incidence is so small that we really can’t make that determination yet.


Are there risks getting the vaccine for people with “long hauler” symptoms?

The short answer is “we don’t know yet.” We’re still trying to figure out what causes long hauler symptoms, and people with a known history of COVID have been excluded from vaccine trials. Because vaccine induced immunity looks like it will be longer-lasting than natural immunity (based on trends in antibody titers over several months), the current blanket recommendation is that people who previously had COVID should get the vaccine, as long as they don’t have a contraindication like known allergy to one of the vaccine components or a history of anaphylactic reaction.


Will these vaccines work against other coronaviruses like SARS-CoV-1 and MERS-CoV?

I’m not aware of any data (or even speculation) regarding potential efficacy of the vaccine against other coronaviruses. SARS-CoV-1 only exists now in laboratory samples, and I hope we will never have the opportunity to collect real-world data on it (its mortality rate was around 10%, compared to 1-2% for SARS-CoV-2). MERS-CoV is so sporadic and mostly isolated to the Arabian peninsula that we don’t really see enough cases to gather good vaccine efficacy data. My suspicion is that the SARS-CoV-2 vaccine would not be protective against other coronaviruses.


Why do we even need a vaccine for a disease with such a high survival rate?

Current estimated case-fatality ratio (number of deaths over number of known cases) in the US is around 1.8% - about 18 times higher than seasonal flu. That number is probably somewhat of an overestimate due to all the unrecognized cases of mild or asymptomatic COVID-19 out there, but it’s still relatively high. The bigger problem for our healthcare infrastructure is the 5% of patients who become critically ill but don’t die, plus the estimated 14% with non-critical severe disease requiring hospitalization. For a novel, rapidly-spreading disease with no pre-existing immunity in the population, this proportion of patients could easily overwhelm our existing hospital capacity and has already done so in some places like Los Angeles. When this happens, we start making difficult decisions like “who gets the last ventilator in the hospital?” and people who might have pulled through their critical illness end up dying. Widespread vaccination on top of existing masking and social distancing measures can help keep patient volumes manageable and mortality down.


The brief summary is that these mRNA vaccines are safe and effective. A tiny fraction of people may have a significant allergic reaction to the vaccine, and we’re still trying to work out what triggers that and who is at risk. However, the way I see it, a small proportion of people will have some kind of weird, unexpected reaction to any medical treatment – it doesn’t mean that the treatment is wholly unsafe. The reactions related to COVID vaccines are pretty rare and getting an incredible amount of coverage largely because COVID has consumed our lives for the better part of a year. I got my first dose of the Moderna vaccine on 12/30, and all I experienced was soreness at the injection site that was probably a little beyond what I usually experience with a flu shot. It still subsided within a couple of days. The faster we reach herd immunity, the sooner we can return to some sense of normalcy, and widespread vaccination is our best way to reach that goal.

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