Just a few days after the UK’s vaccinations began, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) allowing use of an mRNA vaccine made by Pfizer and BioNTech, and continues reviewing the application of another. Four other vaccine candidates in the U.S. are in phase 3 trials, the final phase before a vaccine is submitted for approval.
It’s been a whirlwind, but the next whirlwind is just beginning: actually getting vaccines to the public. The U.S. will need enough doses to vaccinate about 300 million people, estimated Saad Omer, PhD, MBBS, director of the Yale Institute for Global Health, which means 600 million doses if all the vaccines ultimately approved require two doses. As countless public health experts have said throughout the pandemic, vaccines don’t save lives — vaccinations do.
قال Amber Cox ، دكتوراه ، مدير علم الأوبئة للصحة العامة في Maximus Public Health ، وهي شركة خاصة تشارك مع الولاية المحلية والولاية: “إن طرح Covid-19 القادم سيكون أول محاولة على الإطلاق لتطعيم جميع سكان الولايات المتحدة. ، والحكومات الفيدرالية لتنسيق وتقديم الخدمات الصحية. علاوة على ذلك ، يتم تنفيذ هذا الجهد على خلفية الانقسامات السياسية والاجتماعية والاقتصادية العميقة التي تحدت ثقة الجمهور في الحكومة واستجابة مجتمع الصحة العامة لـ Covid-19. سيكون لدى الجمهور الحذر أسئلة – الكثير منها “.
Keep in mind, however, that many of the answers are unknown or aren’t definitive. Uncertainty is an inherent part of scientific inquiry and the scientific process, just as it’s an unavoidable part of finding our way through a pandemic and vaccinating more people at one time than in our nation’s history.
In fact, public health officials are already trying to prepare folks to expect some level of confusion and change.
“As soon as these things start rolling out, we need to anticipate there’s going to be confusion,” said R. Alta Charo, JD, a professor of law and bioethics at the University of Wisconsin, Madison. “It’s going to be incredibly important there’s a single clear message at the federal level about what steps they are taking and what steps come next.
At the state level, officials have to be really open and transparent about why some groups go first and another doesn’t, how they’re making these decisions, and then, crucially, that these are not fixed in stone, that these will change as new vaccines come online, with different profiles for risk and benefit for different groups as we see outbreaks here and there.
Change doesn’t mean we were wrong, it means we’re adapting on the fly, as the situation changes, which is what a responsible health department would do.”
The biggest challenges to the Covid-19 vaccine rollout, Cox said, are trust in institutions, perceived safety of the vaccine, real safety of the vaccine, and access to the vaccine. Elemental has attempted to address all four of those issues and more in the answers below.
Throughout the answers, we frequently refer to different phases of trials, so if you’re unfamiliar with the differences, it may help to read this explainer first. In short, phase 1 trials enroll a small number of healthy people to test whether a vaccine appears initially safe and induces an immune response.
Phase 2 enrolls more people and looks at safety and dosing. Phase 3 involves tens of thousands of people and looks at safety and the vaccine’s effectiveness against the actual disease. For other vaccine-related terms and acronyms you may not know, there’s a glossary at the end.
- Edward Belongia, MD, director of the Center for Clinical Epidemiology & Population Health at Marshfield Clinic Research Institute, Marshfield, Wisconsin
- Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development, Houston, Texas
- Noel Brewer, PhD, professor of health behavior at the University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina
- R. Alta Charo, JD, professor of law and bioethics at the University of Wisconsin, Madison
- Amber Cox, PhD, director of Public Health Epidemiology at Maximus Public Health, Reston, Virginia
- Devon Greyson, PhD, assistant professor of communication at University of Massachusetts, Amherst
- Margaret “Peggy” Hamburg, MD, former commissioner of the U.S. Food and Drug Administration
- Matthew Memoli, MD, director of the Laboratory of Infectious Diseases Clinical Studies Unit at the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
- William Moss, MD, executive director of the International Vaccine Access Center and professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- René Najera, DrPH, an associate in the epidemiology department of the Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
- Paul Offit, MD, director of the Vaccine Education Center and professor of pediatrics at Children’s Hospital of Philadelphia
- Saad Omer, PhD, MBBS, director of the Yale Institute for Global Health, New Haven, Connecticut
- Dorit Reiss, PhD, professor of law at the University of California Hastings Law School
Editorial note: Quotes from R. Alta Charo, Michele Andrasik, and Margaret “Peggy” Hamburg are from a SciLine webinar. William Moss and Rupali J. Limaye spoke during a Johns Hopkins Bloomberg School of Public Health media webinar briefing. Paul Offit and Noel Brewer spoke during a webinar from the American Public Health Association, and C. Buddy Creech spoke during a webinar of the Infectious Disease Society of America.
Q: Are we really going to get a vaccine in early 2021?
Yes—we already do! Late on Dec. 11, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) that allows use of an mRNA vaccine made by Pfizer and BioNTech. An estimated 2.9 million vaccines will be shipped over the subsequent week. The decision came the day after the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) reviewed data on the vaccine’s safety and effectiveness and recommended the FDA issue an EUA. The FDA is continuing to review another vaccine candidate, an mRNA vaccine made by Moderna, who submitted their EUA request to the FDA November 30. Both these vaccines met the minimum requirement by the FDA of at least two months of data after vaccination and efficacy of at least 50%.
After the FDA approves a vaccine, whether through the traditional method or under an EUA, the next step is reviewed by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention. It’s likely ACIP will issue its recommendations on who should get the vaccines very soon. An estimated 40 million vaccines — enough for 20 million people to get two doses each — are already set aside for distribution.
Q: What other vaccines are likely to head to the FDA soon?
The Pfizer/BioNTech vaccine crossed the finish line first, likely to be followed by Moderna, but other contenders are close on their heels. Five of the 12 vaccine candidates in phase 3 trials — the final phase before the company can file for FDA approval — are in the U.S. AstraZeneca and the University of Oxford published data from their phase 2/3 trial in The Lancet on November 19 and are currently preparing to submit their vaccine for approval to the FDA and regulatory authorities in other countries. The two vaccines developed by Novavax and Janssen are likely to follow, depending on what their trials show.
“It may be that other vaccines in the pipeline turn out to be better than these front-runners,” Moss said. “These front-runners aren’t the optimal vaccines. We would ideally have a vaccine that doesn’t have the stringent cold chain requirements that the mRNA vaccines require.
Ideally, we’d have a vaccine that conferred long-term protective immunity after a single dose rather than two doses. And we also want to make sure we have the optimal vaccine for different subpopulations.”
Even if the FDA greenlights all five of these vaccines, it could also end up approving any of the other eight vaccines currently in phase 1 or 2 trials. After all, there are currently 10 licensed flu vaccines in the U.S.
Q: If the two mRNA vaccines get approved, why would we need so many other vaccines?
Right now, we don’t know how many
vaccines we will ultimately end up with, but Omer hopes it will be at least three or four.
“When you deploy a new vaccine, you want to make sure you hedge your bets,” he said. “In case you discover something in post-marketing surveillance, if you have to pull one from the market, you still have others. It’s too important to be a one-vaccine market.”
It’s also particularly important to have different options in a diverse population. “We may learn that certain types of vaccines are better in certain populations,” Moss said.
Q: Does the release of a vaccine mean things will get back to “normal” soon?
Things will eventually get back to normal, but it will take more than a few months, and it will be gradual, explained Moss. “These vaccines are not going to be the silver bullet that brings us back to the pre-pandemic period. We’re still going to need, particularly in the months going forward, to continue to wear masks, socially distance, wash hands frequently, and avoid large gatherings. I think we’ll see over the course of 2021 a more phased return to our normal pre-pandemic life.”
Q: Can I go back to my pre-Covid lifestyle (no masks, going wherever I want, meeting with groups, traveling) once I get the vaccine?
It will continue to be important for everyone to wear masks in public or around other people until large enough numbers of people have gotten the vaccine or the disease has stopped spreading through communities. It’s impossible to tell by looking at someone whether they’ve been vaccinated, so it would be impossible to effectively enforce mask mandates if only unvaccinated people were required to wear masks. (There aren’t plans to issue bracelets like those seen in the movie Contagion or anything similar.) Further, no vaccine is 100% effective, and we don’t yet know if any of the vaccines prevent transmission, so it might be possible to catch or transmit the disease even if you have been vaccinated.
“People have to understand that this is not a magic wand,” said Peggy Hamburg, a former commissioner of the U.S. Food and Drug Administration. “Once the vaccine starts to go out to priority populations, that doesn’t mean that suddenly we can abandon all of the other activities that are so important in terms of reducing rates of infection and controlling spread. It’s going to take time for the vaccine to get to everyone that needs it, and the vaccine will not be fully protective against infection and disease. We are still going to need to do those things that work, including wearing masks and social distancing.”
It’s possible that the more people who get vaccines, the more restrictions can be gradually loosened for restaurants, group gatherings, and similar activities, but it’s not going to happen overnight. Plan to continue following the CDC’s and other health experts’ recommendations as much as you can. Perhaps we can leave our masks at home by late 2021, but it’s impossible to say for now.
Q: How does the development and approval process of a Covid-19 vaccine compare to other vaccines in terms of the regulatory process?
Vaccines typically go through a lengthy FDA approval process that requires copious amounts of completed phase 3 trial data and can take many months. However, during a public emergency, the FDA can issue an Emergency Use Authorization (EUA) to allow use of an unapproved vaccine while trials are ongoing as long as the vaccine meets certain criteria (including the benefits outweighing the risks) and no alternatives exist. The FDA laid out the criteria for Covid-19 vaccines in October, including an efficacy of at least 50% and safety data for at least two months after complete vaccination.
EUAs have existed since the 1930s, but it wasn’t until 2004, following the 9/11 attacks and concerns about bioterrorism, that vaccines could receive them. Using EUAs for Covid-19 vaccines has critics, but the FDA still requires safety and effectiveness data from tens of thousands of trial participants before granting an EUA. Most importantly, the FDA still requires the VRBPAC — composed of independent experts who are not FDA employees — to review the vaccine data before deciding on an EUA.
Q: How has this vaccine been developed so quickly compared to past vaccines?
One of the biggest questions many people have is whether pharmaceutical companies or the FDA have cut corners in developing these vaccines so quickly. The name “Operation Warp Speed doesn’t necessarily engender this comfort and ease with the process,” said Michele Andrasik, PhD, director of social and behavioral sciences and community engagement at the Covid-19 Prevention Network at the Fred Hutchinson Cancer Research Center. “It’s been really important to tease apart which processes are being sped up.”
Indeed, this vaccine has been developed faster than any other in human history, Omer said. But that doesn’t mean corners were cut. “There have been attempts to interfere in Warp Speed, but at the core of it, the integrity of the vaccine process has been preserved,” he said. “It has been expedited by finding efficiencies in the process.”
There are two bottlenecks in prior vaccine development that Covid-19 trials cruised through.
“One of the reasons we’ve been able to move so quickly is the incredible financial investment,” said Devon Greyson, PhD, an assistant professor of health communication at the University of Massachusetts, Amherst. “Things usually take longer because we wait and see before taking the next step.”
The federal government invested nearly $10 billion in Operation Warp Speed. That enabled researchers, once they had enough data to know the vaccine was safe and induced an immune response, to move to phase 3 trials before phases 1 and 2 had even ended. It also allowed them to run combined phase 1/2 or phase 2/3 trials instead of each separately. “That doesn’t change the amount or length of follow-up we have,” Greyson said. “It just means that we were collecting things at the same time that we would have collected one after another, for financial reasons.”
Though this has long been common in cancer drug trials, it occurs less frequently in vaccine trials, which don’t usually have the urgency of cancer trials. Abundant funding also enabled researchers to enroll huge numbers of people in the phase 3 trials, which allows them to learn faster how effective the vaccine is.
The bigger trial-related holdup is usually waiting for enough infections to occur during phase 3 to learn how effective the vaccine is. The rarer a disease is, the longer it takes for enough people to become sick in both the placebo and vaccine arms. But Covid-19 cases shot up this summer and are especially exploding right now. In a sadly ironic twist, the huge numbers of new infections are “good” for a vaccine trial because it takes less time for enough trial participants to get sick and see how well the vaccine works.
Finally, most vaccines require growing the virus in eggs or cell cultures in a lab, which can take many months. (Large quantities of flu vaccines take six months to make.) But mRNA vaccines only require manufacturing short mRNA strands based on the virus’s genetic sequencing. Once that genomic sequence became available in January, researchers could create those genetic strands in a few weeks, dramatically speeding up the process of actually manufacturing the vaccines.
Q: If another country has a proven vaccine first, can we use it?
If you are in that country and qualify for it under that country’s guidance, that’s up to you, but it won’t be possible to get any vaccines in the U.S. that have not undergone review by the FDA and received CDC recommendations.
Q: How will I know if the vaccine is really safe?
It’s not surprising that many people have questions or uncertainty about getting a Covid-19 vaccine. “It’s entirely reasonable to have doubts and concerns,” Greyson said. “We tell people to question interventions, especially new ones, and this is an intervention, and it’s a new one.”
Further, the speed at which these vaccines were developed is “amazing but understandably can be scary if we don’t understand how they were done faster,” Greyson said. “Usually when we talk about things going fast, they’re rushed, we skip steps. In this situation, that’s not the case, but that hasn’t been effectively communicated to the public.”
Here’s how we can know steps were not skipped with these vaccines: Every expert on the planet can review the data themselves. In addition to the two committees of independent experts who will review the vaccine data — VRBPAC at the FDA and ACIP at the CDC — all the clinical trial data submitted to the FDA and CDC will be made available to the public. Pfizer’s data went public December 8 — a whopping 92 pages of it. Other experts can read it and raise any red flags they come across. If you don’t know which experts to follow, Omer has a simple rule of thumb: “Do what Fauci says. He’s a shorthand for outside experts.”
Since other countries are reviewing data for the same vaccines, those who don’t feel confident about the FDA or CDC can look to regulatory agencies overseas for their verdicts on the vaccines’ safety.
Q: What kinds of side effects could the vaccine have?
All vaccines can have reactions and side effects. Side effects are unexpected responses to the vaccine that are uncomfortable or painful but are usually rare. Reactions, especially soreness, swelling, or redness at the injection site, are much more common and are expected to occur in some people after vaccination. Other reactions reported from Covid-19 vaccines include headache, nausea, muscle stiffness, soreness, and aches — all of which are common with many vaccines.
“These are not really side effects in the way that we think about them,” Brewer said. “These are routine reactions that your body has.”
Reactions typically occur because of the way vaccines work — by stimulating the immune system. Illness symptoms like coughing, sneezing, fever, runny nose, and watery eyes are actually the immune system’s response to a pathogen, trying to get rid of it. A fever occurs when the body heats up to help the immune system work more efficiently. Coughing and sneezing are the body’s attempts to literally eject intruders from your body.
Therefore, when these symptoms occur after a vaccine, it’s most often because the vaccine worked (though not necessarily always, as these reactions can occur in placebo groups as well). That is, the vaccine caught the immune system’s attention, and the immune system got to work defending against what it thinks is the real virus.
“The immune response needs a better public relations team because this is just what happens when you respond to a foreign protein, the SARS-CoV-2 spike protein,” that the vaccines cause your cells to produce, Offit said. “When you respond to a natural infection or you respond to an immunization, your immune system makes a series of proteins that cause side effects. That means you’re having a vigorous immune response.”
So while these reactions aren’t pleasant for many—and downright miserable for some—the good news is that they usually mean your immune system is working well. It’s also why many people feel tired or worn out for a few days after getting a vaccine: Your body used up a lot of energy fighting a serious threat (or so the immune system believed it to be).
Most people experienced only mild or moderate reactions, if any, from the Moderna vaccine, but the company hasn’t yet released its complete data on side effects, so it cannot be compared to the Pfizer vaccine right now. Moderna did report numbers for severe adverse events: about 2% developed high fevers (102ºF–104ºF) and severe chills. Other severe Moderna vaccine reactions included severe fatigue (10% of participants), muscle pain (9%), joint pain (5%), and headache (5%). Likely a much higher percentage experienced mild or moderate versions of those side effects, but we won’t know until the company releases the full data.
With the Pfizer vaccine, the younger participants were, the more commonly they reported similar reactions: fatigue, headache, muscle pain, chills, joint pain, and fever. Among the small data set of 100 adolescents aged 12–15, for example, 14% experienced a fever after the first dose, and 20% experienced one after the second dose, compared to 1% and 11% in older adults (over age 55). It‘s not necessarily surprising that older adults would experience fewer reactions than younger people since reactions usually result from how strongly the immune system responds; the older you get, the less efficiently your immune system responds to threats.
The most commonly reported adverse events with the Pfizer vaccine were headache (42% of participants with the first dose and 52% with the second) and fatigue (27% and 59%), which also occurred in the placebo group, though at lower rates. One common theme that occurred across all ages was a stronger reaction to the second Pfizer dose than the first. A majority of participants reported pain at the injection site with both doses. But more than half of participants of all ages felt fatigued after the second dose, and high numbers experienced headaches as well. In those aged 16–55, more than a third experienced chills and/or muscle pain, and the numbers were only slightly lower in those over age 55. A small proportion of participants (less than 1%) experienced severe fatigue, headache, muscle pain, joint pain, or fever with the first dose, and only slightly more (2% or less) had these severe reactions with the second dose, except 3.8% who had severe fatigue with the second dose.
The adverse reactions reported in the AstraZeneca vaccine trials are similar—fever, chills, fatigue, headache, muscle aches, nausea, joint pain, or generally feeling crummy—though complete phase 3 data are not available yet.
One severe adverse event occurred in the AstraZeneca trial: a person developed transverse myelitis (an inflammation of the spinal cord) 2 weeks after getting the second dose, though researchers could not determine if it was related to the vaccine or not. The person recovered and remained in the trial. Not enough data from other vaccine candidates are available yet, but they’re likely to be similar unless an unexpected adverse event is found.
If you get a Covid-19 vaccine, odds are high that you’ll have a sore arm. In addition, some people will have severe swelling at the injection site, and others will feel knocked flat for a day or two, as though they’ve gotten sick, especially after the second dose of an mRNA vaccine. They haven’t gotten sick or been given Covid, but their immune system doesn’t realize that and has gone into overdrive to protect the body. It’s helpful to be prepared in case you’re among the unlucky ones who has a severe reaction, but know that it passes within 1–3 days.
Some experts recommend that people plan for stronger reactions to the second dose by getting it on a Friday or taking off work the next day.
So far, none of the vaccines have shown more serious reactions or side effects than these in the trials, but two people in the United Kingdom did experience severe allergic reactions after receiving the Pfizer vaccine. (See the next question.) Researchers will continue to look for adverse events in trial participants for several years, and the CDC has several surveillance systems to look for and respond to vaccine safety concerns in the general public.
Q: After the severe allergic reactions seen in two U.K. vaccine recipients, should I avoid the vaccine if I’ve ever had a severe allergic reaction to anything?
Early in the Pfizer vaccination program in the U.K., two people experienced serious allergic reactions after receiving the vaccine. Both recovered, and both had a previous history of serious allergies that led them to carry adrenaline shots (EpiPens). U.K. regulators have since suggested that others with a history of serious allergic reactions should not get the vaccine, but that broad recommendation may be premature, explained Offit.
“I think that was an unfortunate move on the U.K.’s part because I think it just scared people unnecessarily,” Offit said. “I think it would have been more reasonable to actually look a little more carefully at those two patients to see what component, if any, in that vaccine caused an allergic reaction.”
Hopefully, scientists in the U.K. are investigating those reactions further, and the U.K. authorities may revise their recommendation after learning more. After the vaccines receive approval in the U.S., the CDC’s ACIP committee will include in its recommendations which groups should not get the vaccine.
Q: What about long-term side effects that we don’t know about yet?
It’s rare for a vaccine to have any side effects more than two weeks after getting it, but there are a few instances that have occurred with past vaccines. The 1976 swine flu vaccine had an increased risk of Guillain-Barré syndrome (GBS), a nerve disorder (one case per 100,000 people vaccinated).
The seasonal flu vaccine has been linked to a small increased risk of GBS as well some years, but it’s in the neighborhood of one or two cases per million, and the risk of GBS from influenza infection is several times higher. Another example is the rotavirus vaccine, which was linked to a very slight increased risk of intussusception, a bowel problem that sometimes requires surgery to treat. One of the H1N1 flu vaccines distributed exclusively in Europe had an added ingredient to enhance the immune system, called an adjuvant, that was linked to increased risk of narcolepsy.
All of these longer-term, rarer side effects occurred within a few months of the vaccine and were picked up quickly by vaccine safety surveillance systems. Many of the mRNA trial participants have already been vaccinated for up to four months. No U.S.-approved vaccine has shown serious long-term effects more than a few months after vaccination, and it’s difficult to determine a biological reason that might happen.
Companies needed at least two months of follow-up to apply for an EUA from the FDA, and by the time a vaccine is available for you, many more months will have passed when researchers gathered more data.
It’s valid and reasonable to have questions about possible long-term effects that occur several months after a Covid-19 vaccine, so researchers and regulatory officials are closely monitoring vaccine recipients to look for any. Continue to follow the news as the vaccines roll out to find out if any long-term effects get reported, but based on the history of vaccines in general, it’s not likely they will.
Q: Are there any medications that would interact with a Covid-19 vaccine?
In the data reported thus far, researchers haven’t found any interactions with other medications in the clinical trials. However, all of the trials except one (Janssen) excluded people who are taking immunosuppressant or immune-modifying drugs, such as those commonly prescribed for cancer and autoimmune diseases. The trials also excluded people who are taking anticoagulant (anti-clotting) and antiplatelet medications.
That means no safety or effectiveness data is available for people in those groups. When the CDC makes its recommendations, it will specify if people taking any specific medications or undergoing specific therapies should avoid vaccination.
Q: Is the vaccine safe for children? When will they be able to get it?
Vaccines must be shown in clinical trials to be safe and effective in children before the FDA will allow their use in children or the CDC will recommend them. Pfizer has begun testing in children aged 12 and older, and Moderna recently announced plans to test its vaccine in 3,000 teens. If those trials go well, they may go on to conduct trials in younger children, following a pattern typical in drug and vaccine trials in general.
“They’re first tested in adults, then older children and adolescents, and we kind of work our way down to younger and younger children,” Moss said. It’s unclear when the other companies will begin testing in children, but it will only occur after there is adequate safety data in adults. “I’m hopeful that by the school term of fall 2021, we will certainly have a vaccine we can administer to children over 12, and I think we have a good shot of having a vaccine for even younger children as well,” Moss said.
Q: How can I be sure that the process of the vaccine’s development and approval wasn’t inappropriately influenced by political interests?
After evidence surfaced of the Trump administration’s meddling at the CDC and given criticism of the administration pressuring the FDA to grant an EUA to hydroxychloroquine (which was later revoked), it’s reasonable to have concerns about political influence in the Covid vaccine development process. Fortunately, several safeguards in the vaccine approval process — even for an EUA — are reassuring.
“One of the things that I point out is that yes, there have been instances [in the history of vaccine development] where scientists have been unethical, and these safeguards are in place to really limit the ability of any one scientist in being unethical,” said Andrasik.
Two of the biggest safeguards are the VRBPAC and ACIP committees, both of which are made up of independent experts who are not employees of the FDA or the CDC and both of which hold open meetings available to the public. For example, President Trump issued an ultimatum to the FDA on Dec. 11, demanding that the agency approve the Pfizer vaccine or he would fire FDA Commissioner Stephen Hahn, a move hardly reassuring to those who want the agency to make its decisions without political pressure. However, by that point, the vaccine had already been approved by the UK’s regulatory agency and had been reviewed by VRBPAC, which found its data on safety and effectiveness strong enough to recommend the FDA issue an EUA. The FDA nearly always follows VRBPAC recommendations, and the President has no ability to influence VRBPAC’s independent members.
In addition, every vaccine trial has an independent safety monitoring board responsible for overseeing the safety of the trial.
You may have heard of some vaccine trials that were paused while an adverse event was investigated. That means the process is working: If someone has a heart attack, the trial stops vaccinating new participants until the study leaders can determine if the heart attack could have been related to the vaccine. Once it’s determined that a serious medical event is not related to the vaccine, the trials resume.
Finally, look to regulatory agencies outside the U.S., Greyson said. “I think something that we in the United States lose sight of is that many, many other countries around the world are also assessing Covid-19 vaccines, and if you’re worried about whether you can trust your own country’s institutions, you can look at other countries to see if they’re also approving those vaccines,” she said. “If they are, you can have more confidence that the approval wasn’t made inappropriately or under political pressure.”
Q: Will any other authorities be looking at the safety and effectiveness of the vaccine besides the FDA and CDC?
Yes. In addition to the United Kingdom’s recent approval of the Pfizer/BioNTech vaccine — the first country to approve a well-tested Covid-19 vaccine and begin vaccinating the public — the U.K. will likely approve the AstraZeneca vaccine developed with Oxford University next. The European Medicines Agency (EMA) is reviewing the Moderna and Pfizer vaccines applications, both submitted December 1, and has begun a “rolling review” of the Janssen vaccine. Health Canada has also begun a rolling review of the Janssen vaccine and is reviewing data for three other vaccine candidates. Australia, New Zealand, India, and other countries are also reviewing data for the Pfizer vaccine, and others developed in the U.S.
Q: What happens if I do have a really serious reaction to a Covid vaccine? Will I be compensated?
Very severe reactions to a vaccine are extremely rare, but that doesn’t mean they never happen. Under the Public Readiness & Emergency Preparedness Act (PREP), the federal government has taken into account the possibility that emergency measures to address the pandemic — including vaccines used with an EUA — could potentially cause unforeseen harm. The PREP Act, therefore, includes the Countermeasures Injury Compensation Program (CICP), which may provide benefits, such as medical expenses, lost employment income, benefits to the estate or survivor death benefits, to those who experience an injury and file for the benefits.
After any Covid-19 vaccines receive full FDA approval, they will no longer fall under the CICP program, but they will fall under a very similar one called the National Vaccine Injury Compensation Program (NVICP). The VICP provides compensation to people who experience an injury due to a vaccine. The VICP is a no-fault system, which means if it’s biologically plausible that the vaccine caused the injury,
or it’s a known injury that can occur in extremely rare circumstances from the vaccine (less than one in several million doses), the person receives compensation without having to prove the vaccine caused the injury and without the vaccine manufacturer being found at fault for a faulty vaccine. You can learn more about the differences between NVICP and CICP here.
Q: How effective can we expect the vaccine to be?
First, it’s important to understand that “effectiveness” can mean different things: Most people think of it as preventing infections, but it can also refer to preventing severe disease, death, or transmission of the disease among people who become infected despite vaccination. Most vaccine trials report “efficacy,” how well the vaccine prevents cases of the disease in the trial.
By that measure, the Pfizer/BioNTech and Moderna vaccines have exceeded expectations so far, even so much as to impress Anthony Fauci.
Pfizer/BioNTech reported their vaccine has 95% efficacy based on the 170 cases of Covid that occurred among their 38,000 trial participants. That means for every 100 people who get the vaccine, only five would likely develop Covid if exposed. The Moderna vaccine has 94% efficacy based on 196 cases among 30,000 participants, but it prevented 100% of severe Covid cases.
The AstraZeneca vaccine has lower overall efficacy so far at 70%, but its data has also baffled scientists: Two full doses of the vaccine led to 62% efficacy, but a half dose followed by a full dose had 90% efficacy.
The company plans to gather more data before submitting their vaccine for approval. A bright spot with this vaccine is that a later study looking specifically at older adults found that they responded to the AstraZeneca vaccine just as well as younger adults and actually had fewer side effects.
Also important: Efficacy only refers to how the vaccine performs in clinical trials. Effectiveness — how the vaccine performs in the real world — can only be measured after the vaccine is licensed and a larger, more diverse group of people receive it. Effectiveness is often similar to efficacy for most vaccines, but it depends on many factors. “Effectiveness is highly dependent on the real-world situation,” said Rene Najera, an associate in the epidemiology department of the Johns Hopkins University Bloomberg School of Public Health. “Inequity in vaccine delivery makes it effective in some populations and not in others.”
The vaccine developed by Janssen, owned by Johnson & Johnson, showed a strong immune response from just one dose in early trials, but the company is testing a single dose and two doses in their larger phase 3 trials.
“It’s possible that a vaccine of lower efficacy but with a single dose might do better at a population level than two doses of a higher efficacy vaccine if we have trouble getting two doses into people,” Moss said.
Q: What will the vaccine actually prevent?
Current Covid vaccine trials are measuring how well the vaccine prevents Covid-19 cases — the actual disease with symptoms — but it’s possible for a vaccine to prevent a disease without preventing infection. Infection occurs when a virus successfully begins to replicate in the body, regardless of whether it causes symptoms. Disease refers to actually developing symptoms and experiencing cell damage from the infection.
In a perfect world, vaccines would induce sterilizing immunity, which means preventing infection: If the real virus enters a person’s body, the immune system reacts so quickly that the virus never has a chance to replicate. In reality, most vaccines don’t provide sterilizing immunity, but they do prevent disease and, often, transmission of the disease from one person to another. It’s not yet possible to know whether the Covid vaccines being developed will cause sterilizing immunity or whether they’ll prevent transmission. That’s why it will still be necessary to wear masks and continue social distancing for a while after people begin receiving vaccines.
Some vaccines also reduce the severity of the disease if a vaccinated person develops an infection anyway. The flu shot is a good example of this. Based on data so far, Moderna’s vaccine appears to prevent severe disease even in those who did get sick after vaccination.
Q: Could someone who gets vaccinated against Covid-19 still transmit the disease to someone else?
This is one of the big questions researchers are trying to learn about the vaccines. Even if a vaccine prevents Covid-19 disease, it might still be possible for the virus to enter a vaccinated person, begin replicating, and then be passed on to someone else without the person ever knowing or developing symptoms. The pertussis (whooping cough) vaccine is a classic example of this phenomenon. Scientists don’t yet know if any of the Covid-19 vaccines prevent transmission, but all the trials include mechanisms to investigate whether they do.
Q: Will a Covid vaccine offer better immunity than an infection?
It’s not possible to say for certain yet whether this is the case, but early data strongly suggests it’s likely that at least the mRNA vaccines will be more protective against future infections than having already recovered from Covid. Both the Pfizer and the Moderna vaccines resulted in higher concentrations of neutralizing antibodies (called titers) than were found in people who had recovered from Covid-19. Neutralizing antibodies are those that block an infection entirely when they bind to a cell, and the more neutralizing antibodies your body has, the less likely you are to develop an infection that you can transmit to others.
Q: Do the reinfections we’ve heard about in the news (people who’ve had Covid-19 getting it again) mean that the vaccine won’t work in some people?
No vaccine is 100% effective, so there are some people who will receive the vaccine but not be protected against infection. We just won’t know who they are. This is also why it’s important to vaccinate as many people as possible — to build up herd immunity to protect people who can’t be vaccinated or in whom the vaccine didn’t work. Scientists don’t know enough yet about the rare cases of reinfection in people who had Covid-19 in the past, so it will take time to understand why that occurs and whether it might be related to the immunity induced by vaccines.
Q: How long will protection from the vaccine last?
Are we going to have to get the vaccine every year like the flu vaccine?
We won’t know how long a Covid-19 vaccine’s immunity lasts for a while — however long it takes to wear off in the first trial participants, at least. But Omer said it’s not likely you’ll need it every year. While the virus does change, coronaviruses don’t change at the same high speed as flu viruses (which is the reason new flu vaccines are needed each fall). “It may be that we have to do repeat vaccinations and boosters for a while, but I’d be surprised if it’s an annual vaccine,” Omer said. Further, scientists already suspect immunity from Covid-19 infections might last years, and both mRNA vaccines led to higher antibody levels than seen in people who had recovered from Covid infections.
Q: What percentage of the population will need to get the vaccine to reach herd immunity?
Herd immunity has been a buzzword since the pandemic began, but misunderstanding what herd immunity is and how it can be achieved has been just as prevalent.
Briefly, herd immunity, or community immunity, refers to having enough people in a population who are immune to a specific disease that the disease has trouble spreading much in that population. Herd immunity is essential for protecting people who cannot be vaccinated because of their age or a medical condition, or who can’t mount an immune response even if they receive the vaccine. If enough people are immune, they won’t catch and transmit the disease to others, and the disease is unlikely to spread through enough people to infect one of the vulnerable folks.
But how much is “enough”? There isn’t a simple answer. It depends partly on how contagious a disease is, and that depends partly on people’s behavior, among other factors. Early in the pandemic, experts were estimating that if 60%–80% of the country developed immunity to Covid, that might be enough to substantially slow down transmission and gradually end the pandemic — but at a huge cost. It’s far preferable to achieve herd immunity with a vaccine. Then it depends not only on how contagious the disease is but also how effective the vaccine is and how long immunity lasts, which can vary by person and by vaccine (especially if there are several different vaccines in use).
So what’s the magic number for how many we need to vaccinate against Covid? It’s not really possible to say yet.
“We do not know for sure that herd immunity will be achieved solely with the response to the spike [protein] in the current crop of vaccines,” said Matthew Memoli, MD, director of the Laboratory of Infectious Diseases Clinical Studies Unit at the National Institute of Allergy and Infectious Diseases. “It may require other forms of immunity currently offered only by getting infected or maybe in future vaccines, using other strategies. We do not really know what protection is offered from the vaccine, how long it lasts, which types of people it will not work for, if it prevents transmission, and so on.”
Q: What happens if too many people refuse to get the vaccine?
The ultimate goal in a nationwide — and global — vaccination campaign is to reach herd immunity, or community immunity, where those who cannot receive the vaccine are protected by the high level of immunity in everyone else. If too many people refuse to get the vaccine, we won’t reach herd immunity, and the disease will continue to spread through populations, though at a slower rate, Greyson said.
“The vaccine will not have the kind of community protection we want, and, in particular, vulnerable people in the community, people with immunodeficiencies who can’t mount a response to the vaccine even if they get it, will not be protected,” she said.
But that’s more of a long-term concern if it ends up being a concern at all. In the beginning, vaccine refusal is not the biggest concern. Figuring out the logistics for everyone who wants a vaccine and ensuring the vaccine is equitably distributed across populations are top priorities. Once everyone who wants a vaccine has gotten one, we can focus more specifically on those who still have questions or concerns about the vaccine.
“Internationally, I think, in the end, even if there are stragglers in the beginning with hesitancy, people will accept a safe and effective vaccine,” Greyson said. The HPV vaccine is a good example of one that had a lot of hesitancy at first but which has now been widely embraced as people saw how safe and effective it is.
The best way to head off that kind of resistance and hesitancy is to mount a nationwide, clear, transparent vaccine communication and education campaign, Omer argues. “Operation Warp Speed is $10 billion. The funding for promoting that is zero,” he said. “We need a promotion budget of the same magnitude of the campaign.”
Q: What kind of vaccines are these? How do they work?
All vaccines work on the same basic principle: They introduce a substance into the body that resembles a pathogen (virus or bacteria) and therefore causes the immune system to mount a defense against the intruder. That substance has historically been a weakened or killed version of the pathogen or an antigen. An antigen is a piece of the pathogen that the immune system recognizes as foreign, such as the spike protein on the SARS-CoV-2 coronavirus that causes Covid-19.
The immune system begins defending the body by producing antibodies, proteins that attach to the intruder. Those antibodies are both an identifier of infected cells and a signal that triggers the immune system to begin producing the cells needed to destroy the intruder.
Until now, U.S. vaccines for pre-Covid diseases have been one of four basic types (though these can be further broken down into more precise categories). But only one of the five front-runners for Covid-19 falls in those categories: The Novavax vaccine is a protein subunit vaccine, like the existing pertussis (whooping cough) and flu vaccines; it contains only the spike protein.
Moderna and Pfizer/BioNTech developed messenger RNA (mRNA) vaccines, and they’re the first of their kind to be submitted for FDA approval. Instead of introducing the antigen itself to the body, these vaccines contain the genetic instructions (mRNA) for making the antigen. The mRNA enters the body’s cells, which then follow the instructions to produce spike protein. Once the cells release the spike protein, the immune system recognizes them as foreign, just as if the spike protein itself had been injected. (Though these are the first mRNA vaccines to be submitted for approval, researchers have been working on them, for other diseases, for more than a decade.)
Oxford/AstraZeneca and Janssen developed non replicating viral vector vaccines, another new vaccine type that hasn’t been approved for pre-Covid diseases, but it’s a bit like a cross between mRNA vaccines and subunit vaccines. The process involves adding a gene to a harmless “vector” virus — one that might normally cause a cold but has been genetically modified not to cause any disease. The gene carries instructions for making the spike protein. Once in the body, the harmless virus replicates in cells and produces the spike protein, which kicks the immune system in gear.
Q: How many doses will people need?
The Moderna and Pfizer vaccines require two doses, three weeks apart for Pfizer and a month apart for Moderna. The AstraZeneca vaccine also requires two doses, but the puzzling efficacy data makes it hard to know if the final application to the CDC will require two full doses or a half-dose and full dose. It’s not clear yet if the Janssen vaccine will involve one or two doses. The Novavax vaccine is testing two doses in its phase 3 trials.
Q: What if I don’t come back for the second dose of the vaccine?
Both the Pfizer and the Moderna vaccines require two doses, though some of the other vaccines may require only one dose. If people don’t return for the second dose, the vaccine won’t be as effective, Hamburg said.
“If you’re getting a vaccine that requires two doses, that’s because you need that second dose, you need that boost in order to mount the level of immune response that vaccine can provide, and that second dose really does make a difference,” she said.
Q: Can I get my first dose of one vaccine and my second dose of a different vaccine?
The FDA only approves vaccines to be given according to how they were tested in clinical trials, which then determines how the CDC will recommend they are administered. Right now, the vaccines have only been tested singularly. No study has looked at getting one dose of a Pfizer vaccine and then a dose of the Moderna vaccine, for example. Therefore, people should only get a second dose of the same vaccine they received for the first dose. Later research might find that mixing and matching is safe and effective, as researchers eventually determined with two different types of rotavirus vaccines for children. But until those studies have been done, stick with the same one.
Q: How can I read how the studies are being conducted?
The procedures for every study are published at ClinicalTrials.gov. At that site, type in “Covid-19” in the “Condition or disease” search bar and then “vaccine” and the manufacturer’s name in the “Other terms” search bar, and it will pull up all the Covid-19 vaccine trials for that manufacturer.
In addition, in a move of transparency that’s highly unusual for vaccine trials, companies have published their detailed clinical trial protocols online. The BMJ has collected them all in one place; see the references at the bottom of this editorial. It will also be possible to read the procedures of each trial in detail as the data for each vaccine becomes publicly available after submission to the FDA.
Q: Will the vaccine protect against other coronavirus diseases?
Sometimes a vaccine for one pathogen
offers limited protection against a very similar pathogen, a phenomenon called cross-strain protections. This is most often seen with flu vaccines when several circulating flu viruses share very similar genetic code. But the SARS-CoV-2 virus doesn’t resemble any of the coronaviruses that cause colds.
“We do not expect any cross-protection against other coronavirus infections since the vaccines trigger an immune response to the SARS-CoV-2 spike protein,” Belongia said. “The immune system sees this as distinct from other human coronaviruses with little or no cross-reactivity.
Seasonal coronaviruses cause mild upper respiratory illness, and the focus of vaccine development has been to prevent serious illness due to Covid-19.”
But we can’t completely rule out cross-strain protection against a new coronavirus that comes along later, or even SARS-CoV (which causes SARS) if it returns, said Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development.
“There is evidence, for instance, that because of the genetic similarity between SARS-CoV and SARS-CoV-2, antibodies generated from SARS vaccines or SARS-2 vaccines can cross neutralize both viruses,” Bottazzi said. “This provides initial evidence for the development of multivalent vaccines or possibly universal coronavirus vaccines. This will be the new research moving forward.”
Q: Will the mRNA vaccine change my DNA?
When people hear that the Pfizer and Modern vaccines contain a gene, some worry the vaccine could alter their genome, but your own personal DNA is wholly contained within the nucleus of each of your cells, Offit explained. And that nucleus is locked down pretty tight. “It’s virtually impossible for the messenger RNA to get into the nucleus,” he said. The mRNA only travels through the cytoplasm of the cell — the other material that surrounds the nucleus — to get to the ribosomes, the protein factories of cells. “People think they’re going to be genetically altered,” but that’s not the case, Offit said.
Q: Why do some vaccines need refrigeration and others don’t?
Vaccines must be stored at whatever temperature range keeps the ingredients stable enough to ensure the vaccine remains safe and effective. Companies subject their vaccines to stress testing at different temperatures over long periods of time to determine the vaccine’s tolerance at different temperatures and its shelf life.
The Pfizer vaccine must be kept at the extremely low temperature of -70º C (-94º F), which is literally colder than Antarctica and substantially colder than typical freezers. The Moderna vaccine only requires storage at -20º C (-4º F), which is similar to most household freezers. It’s not possible for the public to know why these two mRNA vaccines require such different temperatures because the companies keep secret the exact specifications of the manufacturing process (to protect their intellectual property). But we do know why mRNA vaccines need refrigeration in general: to prevent the mRNA from breaking down.
Messenger RNA is only a tiny snippet of genetic code designed to last just long enough to deliver protein-building instructions to the ribosomes, or protein factories, of a cell. If it were injected by itself, it wouldn’t make it very far before enzymes in the body destroyed it, as vaccine researcher Margaret Liu described it to NPR, similar to how chocolate starts melting in your hand. So vaccine manufacturers modify it to keep it stable longer and surround it with a protective coating of lipid nanoparticles, like the candy coating on M&Ms, Liu said, so they don’t melt as quickly. This protects the mRNA long enough to make it into cells so it can deliver its message to the ribosomes
It’s possible Pfizer will discover through more temperature stress-testing that the vaccine can withstand higher temperatures, but until they do, the vaccines must remain at the temperatures that Pfizer knows are best for their formulation.
Right now, Pfizer’s vaccine lasts up to six months in a -70º C specialized freezer (though that could become longer as Pfizer tests samples that it stores longer). Pfizer has designed special dry-ice packed crates that will keep the vaccines at those super-freezing temperatures in transit for up to 15 days. Once thawed, the vaccine can be stored up to five days in a refrigerator.
Moderna’s vaccine similarly lasts up to six months at -20º C but can last in a fridge up to 30 days or at room temperature up to 12 hours.
Q: Can someone get Covid-19 from the vaccine itself or shed the virus and give it to someone else after getting the vaccine?
None of the Covid-19 vaccines under development can give you Covid-19 or lead you to “shed” the virus and give it to others. In fact, none of the vaccines being developed for the U.S. even contain the complete SARS-CoV-2 virus in them, so it’s impossible for them to cause a Covid infection.
Q: My friend is saying crazy things about the vaccine that sound disturbing. How can I find out if they’re true?
As has been seen since the start of the pandemic, misinformation, disinformation, and conspiracy theories continue growing out of control. No doubt there will be plenty of bad information floating about on Covid-19 vaccines, and indeed, plenty is already out there. (No, there is no microchip tracker in the vaccine, it does not contain fetal cells, and it will not give you Covid.) Places to go for accurate information include the CDC (which already has a FAQ about Covid vaccines), the FDA, major hospital websites such as Children’s Hospital of Philadelphia’s Vaccine Education Center, and reliable fact-checker websites.
It’s also helpful to begin regularly practicing a technique called SIFT, coined by Mike Caulfield at Washington State University. When you come across a piece of new information and you’re not sure if it’s true:
- Investigate the source
- Find better/other coverage in other news sources
- Trace claims, quotes, and media to their source
This method, described further at Caulfield’s website, will help you sift truth from fiction online.
Q: Who will get a vaccine first?
The CDC’s Advisory Committee on Immunization Practices (ACIP) developed four principles to guide their decisions on who should first receive the vaccine: “1) maximize benefits and minimize harms, 2) promote justice, 3) mitigate health inequities, and 4) promote transparency.” But the CDC is still figuring out how translating these ideals into practical plans will occur.Priority also depends on the goal: reduce deaths first, or slow transmission first?
“If your goal is to maximize the preservation of human life, then you would bias the vaccine toward older Americans,” former FDA commissioner Scott Gottlieb, MD, told the New York Times. “If your goal is to reduce the rate of infection, then you would prioritize essential workers. So it depends what impact you’re trying to achieve.”
All experts agree that the first group to receive vaccines should be high-risk health workers and first responders since they’re directly in daily contact with Covid-19 patients and they’re essential for caring for those patients. The CDC estimates there are 21 million health care personnel, which appears to include lab technicians, cafeteria workers, janitors, administrative staff, and everyone else essential to the operation of a healthcare facility.
The other three high-priority groups designated by the CDC are essential workers, adults with high-risk medical conditions (based on the CDC’s list), and adults aged 65 and older, including those living in long-term care facilities. But each of these groups is large — 87 million essential workers, over 100 million adults with high-risk conditions, and 53 million older adults (though the populations do overlap one another, such as a 67-year-old grocery cashier with high blood pressure) — and ACIP has not finalized preferential order yet.
The U.K. chose to first vaccinate older adults in long-term care facilities, a group currently included in “phase 1a” by ACIP as well. But a couple of ACIP members at the November 23 meeting called for better data on adults in group homes because of the many challenges and possible risks of vaccinating this population, especially when this population was not included in any of the trials and the side effects may be intense for frailer adults. (The U.K.’s vaccination program may very well provide that data.) The committee unanimously agreed, however, that essential workers should be vaccinated next, in phase 1b, ahead of older adults and adults with high-risk medical conditions. Doing so not only helps reduce transmission but also addresses concerns about health inequities since essential workers include a disproportionately higher number of low-wage workers and Black and Latinx workers.
But who is essential? That will be left primarily up to the states, for good reason. For example, Charo said, snow plowers are essential in Wisconsin while air conditioning repair workers are essential in Arizona. Expect to see intense debates over who counts as essential, especially when it comes to public school teachers.
Eventually, we will reach what Omer called the “Oprah approach: You get a vaccine! You get a vaccine! You get a vaccine!”
Q: How will I know when it’s my turn to get the vaccine and how and where to get it?
When you specifically will get a vaccine will depend on your age, underlying conditions, and occupation, as outlined by the CDC. But how will you know it’s your turn? That will depend on what system your state has developed to notify residents.
“Ideally, immunization information systems would help the public pre register for vaccination so they could understand and monitor where they are in the prioritization queue as well as when to begin watching for an email or call to make an appointment,” Cox said. Such a system could also include a contactless electronic consent form, safety information about the vaccine, which vaccine they’re receiving, and when to return if they need a second dose. It’s not clear, though, how many states or counties might be able to pull a system like that together as quickly as needed. It will largely depend on existing infrastructure and systems.
States will also rely on employers, community and faith groups, community clinics, nonprofit organizations, and other groups to help with communication about vaccines and possibly registration and distribution.
And the timeline for rolling it all out? In a November 22 CNN interview, Moncef Slaoui, chief scientific advisor to Operation Warp Speed, suggested a pretty “aggressive” timeline summarized by Ashish Jha, MD, dean of the Brown University School of Public Health. Slaoui suggested 20 million people would be vaccinated by the end of December, 30 million more by the end of January 2021, and that vaccines would be widely available by April or May. All of that, however, is an estimate subject to change.
Q: Will the vaccine actually be free for everyone in the U.S.?
The federal government has committed to making Covid-19 vaccines free for “everyone,” though there’s some uncertainty about whether people without insurance will have to pay an administrative fee of $20–$40, Cox said. According to a federal announcement in late October, those with traditional Medicare or Medicare Advantage plans will pay nothing, including no copay or deductible. Employer and individual plans will also cover the vaccine in full, with no out of pocket costs, as required under the Affordable Care Act. Meanwhile, the federal government has announced it’s setting up a fund to assist doctors, clinics, hospitals, and other providers who are vaccinating people without insurance.
Q: Will we be able to choose which vaccine we get, and will we know which one is best to get?
The vaccines available to you will depend on which ones are recommended for you by the CDC based on your age and health, Omer said. It will also depend on where you are in the vaccine “line” — something still being worked out by the CDC and state health departments — and what’s available in your area.
“Early on, people will probably not have a choice. It’s going to be what’s available,” Moss said.
“But as vaccine manufacturing builds up and the distribution systems are set up, and likely even more vaccines [have been approved], I anticipate that toward the end of 2021, maybe people will be able to choose the type of vaccine.”
Q: Will people who receive the vaccine be tracked?
Hopefully — but not in the way some people think.
“There’s nothing about the vaccine itself that allows the government, pharma or anyone else to track you, but there are a lot of people trying to figure out what systems will be used to track people, which is important if we’re to detect any safety concerns that emerge,” Greyson said. “I’m more worried that we won’t be tracked because we really do need to track as many people as possible so that if someone does have an adverse event, whether caused by the vaccine or coincidence, we need to be able to look into it.”
States are actually required to track and report the distribution of vaccine doses to the FDA since the vaccines are being distributed under an EUA. But there isn’t likely to be a national database with everyone’s names and doses in it. That actually would be a great idea, but the existing infrastructure is so fractured, even within individual states, that it’s just not possible to do right now.
Tracking is also important for ensuring people have gotten their second dose, but the state immunization registries that each state uses for children’s immunization records are lousy for tracking adult immunizations, Omer said. So it will be up to each state how to track who has received the first and then second dose. The federal government will also issue vaccination record cards so people know which vaccine they received and when to return for the second dose.
Q: When will people who got the placebo in a vaccine clinical trial be able to get the real vaccine?
That question is being hotly debated as you read this. When people enrolled in a vaccine clinical trial, they should have received the protocol in their informed consent, which may have stated when they would receive the real vaccine if the vaccine was successful. But sometimes things need to change based on circumstances, ethics, and the need to maintain the integrity of a clinical trial — the ability to continue comparing the vaccinated and placebo groups.
Experts themselves appear split, according to reporting by the New York Times. Anthony Fauci and Francis S. Collins, director of the National Institutes of Health, favor giving placebo recipients the vaccine sooner than later. But members of the WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation argued recently that the “opportunity to obtain reliable evidence about longer-term effects would be destroyed by early unblinding and immediate vaccination of participants assigned to placebo.” Vaccinating the placebo group also makes it difficult to track how long immunity lasts from the vaccine. The longer the trial can run without the placebo recipients getting the vaccine, the more valuable long-term data can be collected.
It’s unclear when the question will be resolved. It depends on what data the FDA will require from the manufacturers for full approval of the vaccines. In the meantime, however, trial participants are not contractually bound to remain in the trial. A condition of participating in any clinical trial is that participants can withdraw at any time for any reason.
If someone thinks they received the placebo and wants to get a vaccine if it becomes available to them, they can choose to do so, but they will need to withdraw from the trial they’re in.
Q: How will vaccines get distributed across the U.S.?
This is the big question. Omer said he was not concerned about the speed of vaccine development once he saw how it was occurring, but what has kept him up at night is the lack of national strategy for deployment.
The primary responsibility for distribution falls to the states, but each state is developing its own plan, Cox said. “The current strategy is for state emergency operations and health departments to use federal CDC prioritization recommendations to tailor their distribution plan to the specific local, geographic, and demographic needs of their communities,” she said.
Right now, the biggest differences among state plans are how centralized or not the state plans are — whether the state determines where all the vaccines go or whether they leave it up to individual county and local health departments.
States will receive vaccine doses based on how many of its residents fall within the highest priority groups for receiving it, regardless of the state’s population, Paul Mango, an official at the Department of Health and Human Services, told NPR in late October.
If a state has twice the health care workers but half the population of another, it will initially receive twice the number of vaccine doses as the higher-population state until more vaccines become available to work through each priority group.
Q: How will the distribution of the vaccine differ in different states?
The distribution of vaccines will be as distinct as each states’ needs are, Cox said, and she provided some examples:
New Mexico has a high rural population and 23 Native American pueblos, tribes, and nations that each have their own sovereign governments and varying health care systems, so that state’s plan discusses how to meet the challenge of distribution across disparate groups.
Alaska is planning to fly vaccine doses to remote and rural villages.
Florida is taking into account that snowbirds may get one dose in Florida but need their second dose in another state.
California is working on ways to ensure migrant worker populations get the vaccine.
West Virginia doesn’t have enough pharmacists and providers and needs to find ways to administer the vaccine to its population given that shortage.
Fortunately, none of the states have to reinvent the wheel. Many of the state plans rely on lessons they learned during the H1N1 flu vaccination campaign in 2009–2010.
“H1N1 gave us an opportunity to create a pandemic playbook and prioritization schedules and sub-prioritizations that we didn’t even think were necessary,” Cox said. Then states pulled those playbooks out again when hepatitis A outbreaks began occurring from 2017–2020, Corinna Dan of Maximus Public Health added. Some states plan to use mobile clinics as they did with hepatitis A immunization. But they still have a Herculean task ahead of them.
“The difficulty many states face is the sheer amount of communication needed prior to an effective vaccination campaign,” Cox said. Those plans must also include ways to communicate safety and risk reduction information if a safety concern arises. “If there is a safety hold or event in one of the vaccines, this would require the state health department to communicate and manage regionally to reduce confusion.”
Q: How are states ensuring that people aren’t left behind in the vaccination campaign?
Nearly every state plan that Cox has reviewed has included how the state will consider health equity in its vaccine distribution plan. That is, the states are looking at ways to ensure that underserved and underprivileged populations receive equal access to the vaccine or even higher priority if they’re in higher-risk groups. But it’s still going to require regular oversight and checking in.
“It’s important for states as they develop these plans to ask themselves, are these equitable rails that we’re riding on? The communities that we need to reach, are they truly going to be served by these resources?”
Brewer said. “For example, pharmacies are being seen as a panacea, and I agree they will do a lot, but pharmacies [often] exclude certain rural areas and certain Black communities.” States and counties will have to look for barriers like these and plan specifically for how to address them, and how each state does that is going to vary dramatically.
Q: What are most likely to be the biggest obstacles that could slow down distribution of the vaccine?
How much time do you have? Honestly, listing all the wrenches that could interrupt or derail vaccine distribution could fill a graduate dissertation, or two. That’s why it’s requiring such a massive mobilization of people across multiple industries and sectors across the nation (and the world) to figure out supply chains, possible challenges, and contingency plans. Here are just three examples:
More than 500 Native American tribes are in the United States, each with its own sovereign government. While Indian Health Service under HHS will help coordinate vaccine distribution, it’s still going to be a challenge to keep communication open among the tribes, IHS, and individual states and counties.
There could be shortages of glass vials, cargo planes, refrigeration units, or other supplies that could bottleneck distribution, just as swab and reagent shortages early in the pandemic slowed down testing.
An estimated 10.5 million–12 million undocumented immigrants live in the U.S., and we can’t stop the pandemic without vaccinating them as well. Requiring identification or placing vaccination clinics close to government buildings may create barriers to this population.
The Pfizer vaccines -70º C temperature requirement calls for specialized refrigeration. In early distribution, many large hospitals may have or purchase these specialty freezers, though that could leave small and rural hospitals without equal access to the vaccine. But it’s not clear yet if more refrigeration units will be needed across the country or if Pfizer’s specialized packaging will be adequate for preserving the vaccine until it’s administered.
Q: What groups of people were NOT included in the vaccine trials?
Early clinical trials typically enroll only healthy volunteers, but phase 3 trials enroll a broader range of people. All of the phase 3 trials excluded people under 18 (until the new Pfizer study for children 12 and older), and pregnant and breastfeeding people. Except Janssen, all the other front-runners excluded people with immunodeficiency or immunosuppression (regardless of the reason) from phase 3 trials. Many, but not all, phase 3 trials excluded people with cancer, bleeding disorders, HIV, uncontrolled chronic disease, past Covid-19 infection, anticoagulant therapy, or substance or alcohol abuse. Future trials may include more of these excluded groups.
Q: Should I get the vaccine if I already had Covid-19?
Some of the phase 3 trials excluded people with a history of Covid-19, but most, including Pfizer’s, included people with past Covid infections, and the Pfizer vaccine showed equal efficacy in people whether they had a past infection or not. The vaccine will most likely be recommended even to those who have had Covid before, Belongia said, since we still don’t know how long immunity lasts or how strong it is after a natural infection.
Offit agreed, noting that the vaccine rollout won’t distinguish between those who have and haven’t had Covid-19.
And because most trials included people with previous infections, we have the safety data to say that getting the vaccine didn’t cause any problems for those who had Covid before. “All you’re going to do is get a boost in your immunity,” Offit said.
The CDC has already noted on their FAQ that people who have recovered from Covid may still be advised to get the vaccine, and ACIP will specify in its recommendations whether people with a history of Covid should or shouldn’t get a vaccine.
Q: I’m participating in a Covid vaccine clinical trial. Can I get one of the other vaccines?
No one can stop you from getting another vaccine as long as it’s one the CDC recommends for your age group and health and it’s available for you to get. However, you will almost certainly need to formally withdraw from the trial you’re in since it would interfere with that trial’s accurate data collection.
Q: Can I get the vaccine if I’m pregnant?
Whether to include or exclude pregnant people in vaccine clinical trials has always been an ethically fraught issue. None of the phase 3 trials for any of the vaccines included pregnant or breastfeeding people, and only a small number of participants became pregnant during the trials. That means we don’t currently have enough data to know whether the vaccines will be safe and effective during pregnancy or whether the vaccine will affect the fetus.
Most current non-live vaccines (vaccines that do not contain a weakened version of the complete live virus) are safe during pregnancy and even allow the fetus to receive some of the mother’s antibodies, providing some protection in the first few months of life.
But the CDC cannot recommend a Covid-19 vaccine during pregnancy until there’s data on its safety and effectiveness, and it’s not clear when we’ll get that.
Most of the data on other vaccines during pregnancy come from large observational studies looking back at women who received a vaccine without knowing they were pregnant at the time.
“We are going to have to learn more about the risk of Covid-19 and any potential risks of Covid-19 vaccines in pregnant women,” Moss said. “It really comes down to weighing the risks and benefits, and that’s not always a simple thing. But we also don’t want to summarily exclude pregnant women from getting the vaccine when it may be a benefit.”
Q: If I’m over 65, will it be safe to get the vaccine and will it actually work for me?
Adults over age 65 are one of the most important populations for Covid-19 vaccination, so all the companies are testing their vaccine in older adults. In fact, older adults are among those groups deemed high-priority for vaccination by the CDC.
Early data from the AstraZeneca vaccine actually show that older adults experienced fewer side effects than younger adults, and the vaccine was equally effective across all adult age groups. After vaccines have received an EUA or approval from the FDA, the CDC will determine which populations each vaccine is recommended for. There will likely be vaccines approved specifically for older adults.
Q: If I have an autoimmune disorder, will the vaccine be safe for me to get?
The simplest answer is that we don’t know yet, Hamburg said. Novavax is the only company so far to exclude people with autoimmune conditions from its trials, but that doesn’t mean there’s enough data on autoimmune people in other trials to draw conclusions about safety or effectiveness yet. When the CDC issues its recommendations, it will specifically state whether people with certain conditions should not get the vaccine.
Q: Will the vaccine be safe for people with diabetes, HIV, high blood pressure, or other underlying conditions to get?
This answer is not yet available either, but there’s a higher likelihood we’ll find out soon. Most of the phase 3 trials allowed participants to enroll if they had diabetes, HIV, kidney disease, liver disease, and most other chronic conditions, so it’s a matter of how many people with each of these conditions were in the trial and whether it’s enough to assess the safety and effectiveness. Again, the CDC will note in its recommendations whether people with certain conditions should not get certain vaccines.
Q: Will the vaccine be safe and effective for people undergoing cancer treatments, taking immunosuppressant drugs, or otherwise immunocompromised?
People in this group are in the same place as those who are pregnant: They were excluded from nearly every phase 3 trial except the Janssen studies, so we don’t have the data to know one way or another about the safety and effectiveness. Moss said he doesn’t anticipate any safety problems, and most non-live vaccines are safe for immunocompromised people to get. The bigger question is whether a vaccine would work for this group. The definition of immunosuppression is an immune system that doesn’t function at 100%, so it may not respond well enough to the vaccine to offer protection. We won’t know until researchers have gathered more data in future clinical trials or from observational trials in the general population.
Q: How do I know the vaccine will be safe for me if I’m Black or Latinx or otherwise not white?
Historically, clinical trials have not enrolled enough Black, Latinx, and other nonwhite groups, resulting in data that may or may not apply to those groups. For example, the human papillomavirus (HPV) vaccine trials did not include enough Black women, and researchers learned later that the HPV strains covered by the vaccine are most common in white women, but not in Black women.
Also historically, Black people, in particular, have repeatedly been exploited and abused by the U.S. medical system, so it’s understandable why Black people may be especially leery of getting a Covid-19 vaccine.
Yet Covid-19 is also hitting Black and Latinx people the hardest, making them a higher priority for vaccination. For all these reasons, many people have called for extra efforts in recruiting Black and Latinx participants to the trials.
“We want to make sure in our clinical trials to recruit diverse populations, broadly defined,” said C. Buddy Creech, MD, MPH, FPIDS, the principal investigator for both the Moderna and Johnson & Johnson phase 3 trials. “We want individual citizens to be able to look at the clinical trial populations and know that someone a lot like them participated in the trials, including racial and ethnic diversity.”
In the Pfizer phase 3 trials, 9% of the participants were Black, 28% were Latinx, and 0.5% were Native American. It would be ideal to have higher percentages of these populations, but enough are enrolled that the company will eventually be able to compare efficacy across different races and ethnicities. (There aren’t enough total infections yet to determine that right now.) But since everyone in the trials has already received the vaccine, enough data does exist to say that the vaccine is equally safe in Black, Latinx, and Native Americans as in white Americans.
Q: Can the government require me to get vaccinated?
Neither the federal government nor any state governments have proposed requiring eligible people to receive the vaccine, and that’s unlikely to change, even after full FDA licensure of the vaccine would make it legal to do so. Anthony Fauci said at a town hall that he doesn’t expect the federal government ever to mandate a vaccine,
and it’s not possible to force someone to get a vaccine. The public blowback from such a requirement makes it politically risky as well.
“Mandates should usually be only a last resort when uptake is too low to provide community immunity,” Greyson said. Though she has heard others bring it up as a fear, she hasn’t heard of any plans for mandates.
Cox agreed that any discussion of mandates is premature right now. “It’s too early to consider mandates before the safety is established, the supply chains are formed, the vaccine distribution is adequate, and we have properly studied and communicated the risks and benefits to the public,” she said. The goal right now is to “focus on making the vaccine available to as many people who want it first.”
There is a historical precedent upholding the government’s right to require vaccination for the good of public health, though. The Supreme Court case Jacobson v. Massachusetts established in 1905 that local health authorities could require vaccination when it was essential for public health, with some exceptions (including medical conditions that prevented safe vaccination). But it’s rare that any governments actually invoke this right. One recent exception was New York Mayor Bill de Blasio requiring unvaccinated residents of certain zip codes to get the measles vaccine during the measles outbreak in 2019, and even that was narrowly limited to the zip codes with the most transmission.
In the unlikely case that a state, county, or city did try to require Covid-19 vaccination after full FDA approval, it would undoubtedly end up in court and possibly back at the Supreme Court, where the result is anyone’s guess.
Q: Is it legal for my employer to require me to get the vaccine?
Generally speaking, employers have wide latitude in requiring working conditions in the interest of health and safety, and courts generally do not second guess an employer’s judgment, including the use of vaccination requirements, according to Dorit Reiss, a professor of law at the University of California Hastings Law School, who specializes in vaccination law.
But there are several caveats to an employer mandate of Covid-19 vaccination. First, it’s not clear whether businesses can legally require vaccination when the vaccine has only an EUA. The law’s language is ambiguous, Reiss said, and employers may be unable to mandate vaccination until after vaccines have received full approval from the FDA. Even at that point, a union or the Americans with Disabilities Act (ADA) could come into play if an employer wants to require workers to get vaccinated.
“If you have a unionized workforce and there’s a collective bargaining agreement, the collective bargaining agreement may limit the ability of employers to require vaccination unilaterally,” Reiss said. “It depends on what the collective bargaining agreement is.”
Second, if someone has a disability, including a medical condition that doesn’t allow them to get vaccinated, then employers are required to provide “reasonable accommodations” unless doing so is a substantial burden, which has a high bar, she said.
But a reasonable accommodation doesn’t necessarily mean the employee can work as usual without being vaccinated.
“A reasonable accommodation could mean those employees only work remotely, or that they need to wear a mask all the time,
or other things that the courts would find reasonable,” Reiss said. “It doesn’t have to be what the employee actually wants.”
Even then, employers may not need to provide reasonable accommodation if the employee is a direct threat to others, and Covid-19 is already considered a direct threat to others right now. Six months from now, however, it may no longer be considered a direct threat, Reiss said, and she would advise any employer to try to offer reasonable accommodations regardless. “They don’t deserve to be put in a position of losing their job or ruining their health if there’s a real medical contraindication,” she said.
Some petitioners who have challenged past vaccine mandates, such as nurses who refused flu vaccines required by their hospital, have argued such mandates violate workers’ rights, but the counter to that, Reiss said, is that other workers deserve a safe workplace.
“The fact that some workers may not want to get the vaccine may put some of their co-workers at risk, so what about that right?” she said.
Finally, for those who have a sincere religious belief that conflicts with a rule, including a requirement to get a vaccine, the Civil Rights Act of 1964 requires the employer to accommodate the employee unless it’s an “undue burden.” Again, however, the accommodation does not have to be what the worker wants, Reiss said. “It can be another reasonable measure that allows the worker to work while reducing risk,” she said.
Until any of the vaccines have received full FDA approval, however, this question is unlikely to come up.
Q: Is it legal for me to have to get a vaccine before activities like concerts, amusement parks, or flying?
The latitude businesses have in ensuring health and safety also extends to customers, Reiss said. Early reports that Ticketmaster would require Covid-19 vaccination for events was quickly refuted by the company, but they are exploring ways to verify vaccination in case any of their event organizers want to require it. Again, however, it likely couldn’t be required until the vaccine receives full FDA approval. It’s too early to tell whether airlines, amusement parks, or other places might require vaccination at that point, but it’s within their business rights to do so.
That said, logistics alone will probably prevent most businesses from even trying to require vaccination. “If we start from the practicality standpoint, it’s extremely hard to enforce something like that,” Reiss said. “There’s also privacy concerns. How are you going to submit to require evidence of vaccination?” Further, if the pandemic has slowed down enough by the time the vaccines have received full licensure, businesses may no longer feel it’s necessary to require proof of vaccination.
Q: Can my college or university require me to get vaccinated against Covid-19?
Most people think of public school when it comes to immunization requirements, but higher education institutions are increasingly considering requirements beyond the usual vaccines required in public school. Reiss mentioned a recent case in which a judge ruled that a college’s flu vaccine requirement was constitutional, though, again, it may only be so after a vaccine has received full FDA approval.
Q: Will children be required to get the vaccine to attend in-person school?
It won’t be possible for children to even receive the vaccine until it’s been tested and approved for use in children. So far, only Pfizer has begun testing the vaccine in children, starting with those aged 12. If the vaccine is found safe and effective in those children, another trial will likely test younger children. No other companies have announced trials in children yet, but they likely will once they have enough data in adults.
Until vaccines are recommended and widely available for children, there won’t be school requirements for them. Once they are widely available, it will depend on each state’s legislature whether to pass a law requiring Covid-19 vaccination for school attendance.
ACIP — Advisory Committee on Immunization Practices, the CDC committee of medical and public health experts who review data on vaccines and make recommendations on who should receive them and when.
Adverse event — any negative health effect that occurs after being vaccinated, whether it was caused by the vaccine or not.
Antibodies — proteins made by the immune system which attach to a pathogen (virus or bacteria) and show the immune system which infected cells to attack.
Antigen — the piece of a pathogen (virus or bacteria), most often a protein, that the immune system recognizes as foreign and which then prompts the immune system to mount a defense against the pathogen.
Cytoplasm — all the material inside a cell besides the nucleus.
Disease — when an infection progresses enough to cause cell damage and symptoms.
Effectiveness — how well a vaccine prevents disease in the real world.
Efficacy — how well a vaccine prevents disease during a clinical trial.
EUA — Emergency Use Authorization, a temporary decision by the FDA to allow the use of a new, unapproved medical product during a public health emergency as long as there is evidence of its safety and effectiveness and there are no alternatives.
Herd immunity — when so many people in a population are immune to a disease that the disease cannot spread very far through the population (because not enough people catch it and transmit it to others); also called community immunity.
Immunity — protection against developing a disease.
Infection — when a pathogen (virus) enters the body and begins replicating by hijacking cells.
Messenger RNA — a small strip of genetic material that gives instructions, like a recipe, on how to build a specific protein.
Nucleus — the structure inside a cell that contains a person’s complete DNA.
Ribosomes — a structure inside a cell that builds proteins (a protein factory)
Side effect — unanticipated adverse health effects that occur as a result of receiving a vaccine.
Sterilizing immunity — a type of immunity that prevents infection when the immune system responds so quickly that a virus never has a chance to begin replicating.
Vaccine reaction — symptoms that occur after being vaccinated as a result of the immune system’s response to the vaccine.
VRBPAC — Vaccines and Related Biological Products Advisory Committee, the committee of independent experts that reviews the data for vaccines and advises the FDA on the vaccine’s safety and efficacy.