What to expect

Coronavirus vaccine side effects: What we know so far and why they happen

Why scientists aren't surprised by the side-effects of three promising vaccines.

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Rising coronavirus case counts across the country are coinciding with a silver lining. For months, the Covid-19 vaccine has been something we wished for. Now, if all goes to plan, it will soon be something we actually receive — Dr. Anthony Fauci estimates the average American could get vaccinated by April 2021.

It's time to start talking about how getting vaccinated might make you feel.

Recently released trial data from three leading vaccine candidates (two from Phase 3 studies and one from a Phase 2 trial) suggest what we can expect.

On Monday, Moderna Inc. released the results of a Phase 3 trial for its coronavirus vaccine. By Wednesday, Pfizer released more data on its Phase 3 trial. Finally, on Thursday, Oxford University and the drugmaker AstraZeneca released the results of a Phase 2 trial — an earlier stage of testing that measures whether the vaccine induces an immune response and hits basic safety benchmarks. The so-called Oxford vaccine appeared to clear both hurdles — its Phase 3 data, which will include people, is expected before the end of the year.

As of now all three vaccines are “well-tolerated” and cause side-effects in line with what scientists were expecting.

The full data has still not been released for the Moderna vaccine and the Pfizer vaccine, and the Oxford vaccine has yet to release Phase 3 data, so these could be subject to change. However, here’s a rundown of what we know so far:

Moderna’s vaccine — The most commonly reported and medically significant side-effects in Moderna’s interim Phase 3 trial data included:

  • Injection site pain after dose one (the vaccine comes in two doses)
  • Fatigue
  • Muscle pain
  • Joint pain
  • Redness at the injection site

Pfizer’s vaccine — Pfizer’s vaccine trial, which concluded their Phase 3 study this week, suggests its most common side-effects were:

  • Fatigue
  • Headache

The AstraZeneca/Oxford Vaccine — These results come from an earlier stage of study, a Phase 2 trial, conducted on 560 adults. The most common side effects for those in the standard dose group included:

  • Fatigue
  • Feverishness
  • Muscle pain
  • Injection site pain
  • Tenderness

These side-effects were more common in those who received the coronavirus vaccine versus those given a control vaccine.

Why do vaccines have side effects?

Vaccines side-effects differ, Paul Offit tells Inverse. He's the director of the Vaccine Education Center at Children's Hospital of Philadelphia.

However, the reason why the two leading vaccine candidates — the Moderna vaccine and the Pfizer vaccine — can cause these expected sides-effects is due to the immune system’s reaction to the way the vaccine is packaged.

These are both mRNA vaccines, which contain the genetic instructions the body needs to make a piece of the coronavirus (the spike protein). That mRNA is unstable on its own, so it's wrapped in a fatty-encasement.

“This sort of complex lipid [fat] encasement, can be reactogenic, meaning it can cause these kinds of side effects including low-grade fever, and the side effects associated with fever, [like] headache, muscle aches, fatigue, chills," Offit says.

“It doesn't usually last more than a day or two."

Vaccines provoke an immune response, which can cause some redness and swelling at the injection site as the body gears up to confront a pathogen (or a piece of one).

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Non-mRNA vaccines come with similar side effects simply because they’re intended to stimulate the immune system. That pain — though it varies by person and by the vaccine — can be a sign that this immune response is happening.

Once a vaccine is injected, the immune system — recognizing a foreign pathogen (or an aspect of one) —responds by recruiting other cells and inflammatory cytokines to control the pathogen. It’s a dress rehearsal for what the body will have to do should it encounter the real pathogen. It can also cause discomfort in the muscle around the injection site.

Are specific people more likely to feel vaccine side-effects?

Sometimes, by-products of that immune system response end up circulating in the blood, which can cause other side effects elsewhere in the body. These are called systemic effects and include fever, fatigue, or headache.

Generally speaking, the strength of that immune response can dictate how intense those symptoms may feel for a day or so.

For example, the Phase 2 trial results of the AstraZeneca/Oxford Vaccine showed that older adults tended to report fewer side effects than younger adults. The Pfizer vaccine’s press release also noted older adults were reporting “fewer and milder” effects compared to younger people.

“Older adults have a more senescent immune system, so they don't respond as vigorously,” says Offit.

“For example, a child can have a temperature fever of 105 degrees sometimes higher. It's very rare for an adult to have that kind of fever.”

It should be noted that older people still appeared to have strong immune responses to the Pfizer, Moderna, and Oxford Vaccine candidates, a critical measure of how successful they will be.

The data on the immune responses of the coronavirus vaccines in children have not yet been released, though AstraZeneca, Johnson and Johnson, Pfizer, and Moderna have indicated that they plan to develop a vaccine for children.

What comes next for the coronavirus vaccine?

It’s fair to want to know the ins and outs of how a vaccine will make you feel. But while looking at these results Offit suggests comparing the effects of a vaccine to the effects of getting the coronavirus.

The discomfort that comes with getting the coronavirus vaccine may last a day or two. It could even cause you to miss work for a day, he notes. That’s often the case with other vaccines, he says — just look at the Shingles vaccine. But the consequences of getting the coronavirus itself are far more drastic, lasting, and unpredictable.

The virus can attack the blood vessels and affect nearly every major organ in the body. It can have prolonged consequences for some people, even the young and healthy.

“I think people should be scared of this virus, not just because it kills you,” Offit says. “But because of the long-term nature of what it can do.”

If feelings of vaccine hesitancy do start to bubble up, remember we are only going to know more about how the vaccine works and makes people feel.

"I think people should be scared of this virus, not just because it kills you,"

The data available right now from Moderna and Pfizer, while promising, are still only press releases. They are snapshots of thousands of patient files that have been collected.

To put things in perspective, when Offit was pursuing a vaccine trial for rotavirus, his team collected data on 70,000 children.

“If you took the clinical reports on each of those children and stacked them one on top of one another it exceeded the height of the Sears Tower,” he says.

Similarly, the companies pursuing these Phase 3 clinical trials have datasets that encompass huge amounts of information, which is part of the reason that scientists are urging companies to release more than the figures presented in press releases. The FDA will have to review a great deal of that data, which means that even those who are the first in line to get the coronavirus vaccine won't be flying blind – they will have the experiences of thousands of others telling them what to expect.

That doesn’t mean there aren’t questions. We still don't know how exactly long immunity will last, says Offit, and the studies — at least right now — can’t answer that question.

At this point, we know that we can expect side-effects that are in-line with what we usually expect from vaccines. And ultimately, it represents a light at the end of the tunnel.

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