Editor’s Note (3/30/21): This story has been updated with new questions and information.

More than 50 million people in the U.S. are now fully vaccinated against COVID-19. In mid-March President Joe Biden said his administration “may be able to double” its initial target of administering 100 million doses in his first 100 days in office. Biden has also set May 1 as a goal for all American adults to be eligible for vaccination. But the lack of informed messaging from the Trump administration—combined with the range of different COVID vaccines, the emergence of new coronavirus variants, and inconsistent state and municipal rollout plans—have caused confusion and driven vaccine hesitancy. Scientific American asked Namandjé Bumpus, a pharmacologist at Johns Hopkins Medicine in Baltimore, and Ashley Lauren St. John, an immunologist at Duke-NUS Medical School in Singapore, to answer some of the biggest questions about the currently available COVID vaccines.

[Bumpus’s and St. John’s answers have been combined and edited for clarity and length.]

Should you get an authorized COVID vaccine now if you are eligible?

Yes! If you are currently eligible to get a vaccine, go ahead and get it. We really need more people to get vaccinated to build herd immunity and slow the spread of disease. Vaccines are an important part of our toolkit for moving us out of the pandemic. If you have individual reasons for hesitation, talk to your health care provider.

Is there a “best” vaccine?

Different vaccine designs are chosen because they have unique advantages, so there is not a “best” vaccine, but there might be a vaccine that is better for a certain group of people to take. Both mRNA and viral vector vaccines instruct your cells to make pieces of the coronavirus spike protein so that the next time your body encounters those proteins, it can mount an immune response. Efficacy numbers are derived from different clinical studies that were done in different settings, so instead of comparing those numbers, the thing to take away is that the authorized vaccines generally work. They have efficacy.

How should you interpret vaccine efficacy—what does “95 percent efficacy” or “66 percent efficacy” even mean?

Vaccine efficacy refers to how well it performs in a carefully controlled trial, whereas effectiveness describes its performance in the real world. A common mistake is to interpret a 95 percent efficacy to mean you have a 5 percent chance of getting sick even if you get vaccinated. That is not true at all. Efficacy is calculated based on trials that have an unvaccinated placebo control group, and at the end of the trial, [researchers] look at the number in the control group that ended up with symptomatic COVID to get the baseline infection rate. The Pfizer-BioNTech vaccine, for instance, had 95 percent efficacy in its clinical trial. That number came from the fact that 162 people in the placebo group got symptomatic COVID, and eight people in the vaccinated group did; that is 170 cases total. Eight is approximately 5 percent of 170. That is essentially how efficacy is calculated. Most COVID vaccine clinical trials have reported efficacy in preventing any symptomatic disease, not necessarily severe disease. Early data for the latter are promising, however.

Is it safe to mix and match first and second vaccine doses from different manufacturers?

The short answer is that we don’t know, so we can’t consider these interchangeable vaccines. People should not mix and match them. We don’t know about the safety or efficacy of the vaccines if they’re mixed. It’s important to stick to the same vaccine if you have a two-dose regimen. They’re not interchangeable at this point.

Should you be worried about allergic reactions to the vaccine?

Allergic reactions can occur in response to any injected vaccines or drugs, but they are extremely rare. The vaccines should always be administered in a setting where health care providers can treat any allergic reactions that develop unexpectedly. People don’t need to be concerned about the vaccines if they have food allergies or latex allergies. Most people don’t need to worry about an allergic reaction. For those with a history of severe allergic reactions or allergies to the vaccine ingredients, it would be best to discuss it with a doctor before getting the COVID vaccine.

What side effects might you experience, and are they normal?

The common side effects are what we would expect for other vaccines: fatigue, headache, fever—particularly after the second dose—and acute pain at the injection site, which can feel warm to the touch and swollen. All of these symptoms are signs of immune reaction. These reactions are very common and often indicate that the immune system is working hard to recognize the vaccine and remember the new virus for next time.

Why do some people have a strong reaction to the second dose of one of the mRNA vaccines or, if they have been infected with COVID-19, a worse reaction to the first dose?

The first dose is priming your immune system; it’s teaching your body how to respond to the SARS-CoV-2 spike protein, [which the virus uses to enter cells]. The second dose is a kind of boost, where your body has been primed to have some response to the second dose. People who had COVID-19 already have that primed immune system, so when they get the first dose, their immune response is stronger—similar to people who have not had COVID when they get the second dose.

The Centers for Disease Control and Prevention says people should avoid taking anti-inflammatory drugs such as ibuprofen or aspirin before getting vaccinated. Why?

For people who are taking these [drugs] for a medical reason—such as people who take aspirin every day—the CDC says they should continue doing so and talk to their doctor. But for other people, who might be trying to preemptively prevent symptoms from the vaccine by taking [these medications] beforehand, they really shouldn’t. We just don’t know what the effects would be, as far as interfering with building immunity [is concerned]. There is really no reason to take them preemptively. Once you have gotten vaccinated and develop side effects, you can take these over-the-counter medicines to try and deal with them.

Should you get vaccinated if you have already had COVID?

The CDC has not suggested a minimum interval between recovering from COVID and getting vaccinated. Your symptoms should be gone, and you should be released from quarantine before you go get a vaccine so as not to give COVID to anyone else. It may be true that you can wait longer because you have some immune response built up—talk to your health care provider if you think that applies to you. [Editor’s Note: In contrast with most public health guidance, White House chief medical adviser Anthony Fauci said he believes people who have been infected should wait 90 days before getting vaccinated.]

If you get the vaccine and get infected, does the vaccine still make a difference? Will it prevent severe disease or death?

Yes, what we’ve seen with most of the current vaccines is less severe symptoms and almost no hospitalizations and deaths in vaccinated people who become infected. Several vaccine trials have observed a reduction in severe disease in the vaccinated subjects. With a few exceptions—such as, possibly, the AstraZeneca vaccine in South Africa—the vaccines appear to reduce your risk of getting symptomatic COVID, but if you do get it, it’s very likely to be a less severe case.

Do the vaccines protect against the new virus variants, including those first identified in the U.K., South Africa and Brazil?

The data so far suggest that most of the vaccines do provide at least some protection against the new variants. We can see from some of the clinical trial data and antibody neutralization studies, however, that vaccines designed against the original strains of the virus might not be quite as effective against certain new variants—particularly against mutations found in the B.1.351 variant that is now widespread in South Africa. Many of the new variants have changes in the spike protein, which the virus uses to infect cells, so it’s a little bit different than what a vaccinated person’s body has seen before in the vaccine. Still, overall, the vaccines authorized in the U.S. are meeting efficacy targets and seem to give some protection against the new variants. The best way to prevent new variants from emerging is to get lots of people vaccinated. Moderna is developing a booster shot to offer additional protection if needed, and Pfizer-BioNTech is exploring this possibility as well.

What is the difference between mRNA and viral vector vaccines?

An mRNA vaccine—such as the one made by Pfizer-BioNTech or Moderna—provides genetic instructions for making viral proteins in the form of single-stranded RNA, in a lipid coat, to your cells without injecting any virus itself. This has some exciting advantages because it only contains those virus components that you want the immune system to recognize, and it causes your own cells to mimic the way viral proteins are made when a cell is naturally infected with the virus. It is remarkably good at inducing the same type of immune response that would occur in a natural infection. A downside is that the mRNA needs to be kept very cold for it to be stable.

Viral vector vaccines—such as those made by AstraZeneca or Johnson & Johnson—use double-stranded DNA instead of RNA but still deliver genetic instructions to your cells. They use a modified, safe virus (not SARS-CoV-2) to deliver the instructions for making viral proteins.

What’s going on with the AstraZeneca vaccine? What can we expect for this vaccine’s authorization in the U.S.?

There are things that have to be sorted out, as far as interpreting the data and making sure the monitoring board has data that are up to date [are concerned]. Even if everything does move relatively quickly, the vaccine may not be authorized for emergency use before May, by which time we expect there will be more vaccines available. So it’s kind of hard to tell. But there is a potentially important role for AstraZeneca to play internationally. It is important to understand the effectiveness in the U.S. even if the vaccine isn’t used widely here, because [those are] still more data that inform the vaccine’s overall performance.

Will the vaccine protect you from giving the virus to others?

We hope so, but we don’t fully know yet. There are two key goals of vaccines: to protect the individual and to stop the spread of disease. We do have reason to be hopeful based on what we know about viruses and some emerging data, but we still don’t know for sure if vaccinations will reduce disease transmission. That is why it’s important to continue social distancing, wearing masks and following other guidelines to prevent the spread of disease even if you have been vaccinated.

Will the vaccine’s effectiveness “wear off” over time?

This could happen. Vaccines often need booster doses to confer the best levels of protection. Some vaccines can protect someone for a lifetime, whereas others require a boost every few years. It will be important to monitor immune responses over time in those who are vaccinated so we will know if and when boosters are needed. Most of the currently available COVID vaccines require two doses to be fully effective. The CDC recently expanded the recommended allowable interval between doses because of limited availability, although some experts have criticized the decision.

How can you ensure you’re getting a legitimate, authorized vaccine?

It is always important to take vaccines under the supervision of a licensed medical provider. Make an appointment with a designated clinic or retail pharmacy where vaccines are available. Check with your doctor about any concerns because there are clear distribution plans for vaccines in most places.

Do we know if COVID vaccines are safe for children?

The initial Pfizer-BioNTech vaccine trial tested people as young as age 16, which is why that vaccine is authorized for 16 and older. The Pfizer-BioNTech [collaboration] and Moderna now have ongoing vaccine studies including children as young as six months, and those studies should hopefully be done by the summer. So there is the potential that these vaccines could be authorized for adolescents in the fall of 2021.

Could we reach herd immunity without vaccinating children?

It’s really hard to know. There are models, but we need to see what transmission looks like once the vaccines are available to everyone. It depends on the virus variants and how well the vaccines perform in real life. We’ll have to see. Because we don’t have a vaccine currently authorized for children, it’s even more important for as many adults as possible to get vaccinated.

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