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    Are they safe? Which one is best? Your COVID-19 vaccine questions — answered

    Vaccine experts weigh in on side effects, efficacy rates, and how the vaccines stack up against the variants.

    A masked woman in a car prepares to receive a vaccine from a masked worker

    Editor’s note: This article was written before the Centers for Disease Control and Prevention called for a pause on the use of the Johnson & Johnson COVID-19 vaccine on April 13. The pause was recommended to allow for further investigation into a rare but serious blood clotting condition that occurred in six women after they received the vaccine. On April 23, CDC advisers recommended that use of the J&J vaccine restart, with a label stating the risk of the condition.

    Ninety percent of adults in America will be eligible for a COVID-19 vaccine by April 19, according to the White House. This means that millions of people will have the chance to line up for their shot in less than three weeks. But what remains to be seen is how many eligible people will take that chance.

    A Pew Research Center survey in late February found that 69% of Americans either have already been vaccinated or plan to be vaccinated. That’s up from the 60% who said they’d get vaccinated last November. Still, 30% of respondents said they would probably or definitely not get a vaccine. The top reasons given for foregoing it were concerns about how well the vaccines work, their side effects, and distrust in the quick development process.

    AAMCNews spoke with vaccine experts to answer common questions about the COVID-19 vaccines.

    How do the vaccines work?

    The United States has authorized three vaccines for emergency use, and a fourth is likely to go before the Food and Drug Administration for approval in the coming weeks.

    Pfizer and Moderna: The first two COVID-19 vaccines to be greenlit in the United States use messenger RNA (mRNA), which is a molecule that instructs human cells to make a piece of the spike protein that the coronavirus uses to attach to and infect human cells. The material from the vaccine quickly disintegrates and never enters the cell’s nucleus, so it can’t alter the recipient’s DNA. The presence of the harmless spike proteins triggers the immune system to create antibodies and activate T-cells that mount an immune response. With the immune system primed, it is ready to act quickly if it ever detects the coronavirus in the body.

    Researchers have been working on mRNA technology since the 1990s to fight a variety of diseases from influenza to Ebola, but the COVID-19 vaccine is the first time this technology has been authorized for the public.

    The Pfizer vaccine requires two doses administered 21 days apart and the Moderna vaccine requires two doses 28 days apart.

    Johnson & Johnson: The third vaccine to receive emergency use approval in the United States uses another relatively new vaccine technology that tweaks a harmless adenovirus — a type of virus that causes a common cold — to deliver the coronavirus spike protein instructions. After decades of research, the first adenovirus vaccine — used to protect against the Ebola virus — was approved in July 2020. Scientists reengineered the adenovirus in the COVID-19 vaccine so that it cannot replicate and make the recipient sick, but it can still deliver the spike protein instructions.

    “It’s kind of like hijacking a known virus,” says Wilbur Chen, MD, an infectious disease and vaccine expert and chief of the adult clinical studies section of the Center for Vaccine Development and Global Health within the University of Maryland School of Medicine.

    The Johnson & Johnson vaccine requires only one dose.

    (The CDC called for a pause using this vaccine on April 13 in order to further investigate its safety after a rare, but serious blood clotting condition that occurred in six women after vaccination.)

    AstraZeneca: This vaccine is not yet approved in the United States, but its manufacturers plan to seek approval in the coming weeks. It works in a similar way to the Johnson & Johnson vaccine, except it uses a reengineered adenovirus that typically infects chimpanzees. The AstraZeneca vaccine currently requires two doses given four weeks apart, but there is some uncertainty about how far apart the doses can be administered. The United Kingdom delayed the second shot to 12 weeks and one study suggests that the longer delay may have strengthened the vaccine’s effectiveness.

    Which vaccine is the best one?

    The experts agreed: The best vaccine is the one that is first available to you.

    “What I tell my patients and family members is to take whatever vaccine you can get,” says Mark Mulligan, MD, a professor at NYU Grossman School of Medicine and director of the NYU Langone Vaccine Center, who led the clinical trials for the AstraZeneca and Pfizer vaccines at New York University (NYU). “They’re all highly effective. You can’t really make any discernment from one to another.”

    Some have speculated that the Pfizer and Moderna vaccines — with their roughly 95% efficacy rates in clinical trials — are better than the Johnson & Johnson vaccine (66% efficacy) and the AstraZeneca vaccine (76% efficacy). But comparing the different vaccines’ efficacy rates is sometimes like comparing apples and oranges, according to Anna Durbin, MD, a professor at Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health in Baltimore who specializes in infectious disease and vaccines.

    “What I tell my patients and family members is to take whatever vaccine you can get. They’re all highly effective. You can’t really make any discernment from one to another.”

    Mark Mulligan, MD
    Professor at NYU Grossman School of Medicine and director of the NYU Langone Vaccine Center

    Efficacy data depends on many factors, including when and where the clinical trials took place, she says. Pfizer and Moderna, for example, tested their vaccines earlier in the pandemic and primarily in the United States before more contagious and deadly variants emerged, while much of Johnson & Johnson’s data was gathered in South America and South Africa, where particularly troubling variants were spreading.

    Another complication is what the researchers conducting the clinical trials were measuring. The efficacy number reported in clinical trials was against any COVID-19 symptoms — even mild ones.

    “What we’re trying to do is prevent severe illness,” Durbin explains. “All of them are close to 100% at preventing hospitalized COVID-19.”

    In fact, experts say that the Johnson & Johnson vaccine has some advantages over the mRNA vaccines, including that it does not require ultra-cold storage and can be given as a one-dose regimen. 

    The Centers for Disease Control and Prevention (CDC) says that a person can consider themselves fully vaccinated two weeks after the single shot of Johnson & Johnson or the second shot of Pfizer or Moderna.

    If a person has previously been infected with SARS-CoV-2, the timeline may be shortened. One study at NYU Grossman School of Medicine found that, in the days following the first vaccine dose, previously infected people produced similar or greater numbers of antibodies than previously uninfected people did after the second shot.

    Mulligan, who led the study, says that the information could suggest that people who have had COVID-19 might only need one shot of the mRNA vaccines, but that requires further study.

    Are the vaccines safe?

    Every vaccine that is approved in the United States, even if under emergency use authorization, undergoes stringent safety testing, and the CDC continues to collect data on any side effects or adverse outcomes that could be related to the vaccine over time.

    People who receive vaccines may experience a number of side effects, such as a sore arm, fever, fatigue, chills, nausea, and body aches — especially after the second dose of one of the two-dose regimens. This is a sign that the immune system is reacting and is not a cause for concern. The CDC recommends taking a painkiller after (not before) getting the shot and exercising the arm to avoid soreness.

    The side effects are generally more intense after the second shot, as the immune system reacts to the known spike protein. The CDC also reports that 80% of those who reported experiencing side effects were women, which may be related to sex hormones’ role in the immune response, according to a New York Times article

    There are some rare serious side effects, such as anaphylaxis — a life-threatening, but treatable, allergic reaction. In the United States, this reaction has occurred in about two to five people per million vaccinated and has not resulted in any deaths.

    The CDC requires that vaccinated people stay at the vaccination site for observation for at least 15 minutes after getting the shot in case they do have a negative reaction.

    Kathryn Edwards, MD, a vaccinologist and the Sarah H. Sell and Cornelius Vanderbilt professor of pediatrics in the Division of Infectious Diseases at Vanderbilt University School of Medicine in Nashville, Tennessee, spends most of her day assessing reactions after COVID-19 vaccines as part of her CDC-funded Clinical Immunization Safety Assessment unit. Her team, which is working with allergists, believes that someone who has an immediate anaphylactic reaction to the first dose of an mRNA vaccine should not receive the second dose of that vaccine but rather may be able to get the Johnson & Johnson vaccine for their second shot with careful monitoring.

    “I’ve been doing this a long time, and I don’t know that I’ve worked any harder than I am now. We want to make sure that the public knows that we want these vaccines to be both safe and effective.”

    Kathryn Edwards, MD
    Vaccinologist and professor of pediatrics in the Division of Infectious Diseases at Vanderbilt University School of Medicine

    Edwards also cautions that not all adverse reactions that happen around the time of vaccination are caused by the vaccine. As people with underlying conditions — particularly older individuals — receive a vaccine, heart attacks or strokes will happen and could be coincidental. Her team is working to determine whether certain reactions are happening more often than would be expected after vaccination.

    For example, there is a concern that came up with the AstraZeneca vaccine that resulted in several countries pausing or limiting its use due to reports of blood clots. Edwards says that the number of people who have experienced blood clots after being vaccinated in the United States so far is lower than what would be expected in the everyday population. Still, the CDC is continually looking at these rates to identify any signal for a reaction that might be associated with a vaccine.

    Though any long-term effects of the vaccines are not yet known, Edwards says that she and the CDC are being vigilant in investigating any potential problems as they arise.

    “I’ve been doing this a long time,” she notes. “And I don’t know that I’ve worked any harder than I am now. We want to make sure that the public knows that we want these vaccines to be both safe and effective.”

    Do the vaccines protect against the variants?

    The optimism that came with the approval of COVID-19 vaccines in late 2020 was tempered by the emergence of several coronavirus variants that had mutated to be more contagious, deadlier, and potentially able to evade the vaccines.

    But the data so far suggest that currently available vaccines work well against the variants.

    Chen says that those who are vaccinated and later infected with one of the concerning variants are still unlikely to be hospitalized. Though there is little real-world data on how the vaccines work against the B.1.351 variant — a particularly concerning one first detected in South Africa — one small clinical trial for the AstraZeneca vaccine was halted after it showed only 22% efficacy against the variant. Notably, none of the vaccinated people, who were generally low-risk for severe COVID-19 to begin with, were hospitalized or died.

    The World Health Organization says that the vaccines are likely to provide at least some protection against each of the variants because they prompt a broad immune response beyond just targeting the spike protein that is the focus of the vaccines.

    Pfizer and Moderna have begun testing third “booster” shots of the vaccines to see if the extra dose could provide further protection against the variants. They are also developing variant-specific vaccines targeting the B.1.351 variant.

    Edwards would not be surprised if it turns out that people need to continue to get COVID-19 booster shots as additional variants emerge.

    “When new strains emerge, we may need to make new vaccines. We have been doing that for many years [for the flu vaccine],” she explains. “We may need to do it for COVID as well.”

    But it is still a race between vaccination and variants. The key to ending the pandemic is getting vaccines administered to people across the globe. As of March 30, there had been only 7.4 vaccine doses administered per 100 people globally, and many low-income countries had not yet administered a single dose, according to the New York Times vaccination tracker.

    “Until the entire world has conquered the virus,” Durbin says, “we’re going to have to keep protecting ourselves.”