Comparing the COVID-19 vaccines: Differences are small, but they do exist

If you get the choice, which COVID-19 vaccine should you choose?

For now, experts are clear: The best vaccine is the one about to go into your arm. But as the vaccine supply grows, Americans eventually might find someone asking, "Which vaccine do you want?"

The answer for most people will still be "Whatever's available." But there are differences that could play a role, though doctors are unanimous that all three currently authorized vaccines work extremely well to protect against severe disease, hospitalization and death.

A shot now is better than waiting for a different shot, said Dr. Kathryn Edwards, scientific director of the Vaccine Research Program at Vanderbilt University's School of Medicine. It likely benefits the individual and society alike by lowering the overall spread of the disease.

Beyond that, there are small trade-offs when it comes to the current vaccines. In general, Pfizer-BioNTech and Moderna vaccines require two doses and are somewhat more effective. Johnson & Johnson requires one dose and is somewhat less likely to cause side effects.

J&J's "one and done" aspect is a selling point for many.

Pedro Betancourt works at the airport in Miami and "can't take chances," he said. His choice would be "Johnson & Johnson due to a convenient one shot." But he said he wasn't picky because he and his wife had gotten COVID-19, which he described as "mild but scary."

Right now, "I hope everyone takes the vaccinations seriously so that we can begin moving forward to normalcy," he said.

Effectiveness: Check efficacy rates

Overall, Pfizer-BioNTech and Moderna had slightly higher efficacy rates in clinical trials than J&J.

That's enough for Tom Cavanagh of Lexington Park, Maryland. Given the choice, he'd choose either of them but would be open to all.

"Having been in the U.S. military, I have gotten many vaccines without having a bit of knowledge, so I will take the vaccine that I can get and hope for the best," he said.

One way to approach this could be deciding if you're someone at high risk of getting very sick or dying from COVID-19 or if someone in your family is, said Hilda Bastian, a health scientist who writes on COVID-19 vaccines.

People in that group might choose the Pfizer-BioNTech or Moderna vaccines.

For someone who doesn't have anyone at home at high risk, and isn't at high risk themselves, that slightly better effectiveness wouldn't matter as much. The ease of the one-shot J&J vaccine could be more important.

"They might think, 'As long as I'm doing my bit for the community, if it's enough for that, then that would be enough for me,'" Bastian said.

Immunity: How fast does it work?

How quickly the vaccines' protection kicks in and how long it lasts are still being worked out. No long-term data is available because none of the vaccines are more than a year old.

The vaccines don't give immediate protection because there are biological limitations at work, said Dr. Otto Yang, a professor of medicine and associate chief of infectious diseases at UCLA's David Geffen School of Medicine.
"It takes time for antibodies and T cells to build to adequate levels. Antibodies in particular also require 'maturation.'" he said.

It might seem the one-shot Johnson & Johnson vaccine, would be faster but that's not necessarily the case.

From published data on symptomatic infections, it appears the Moderna and Pfizer vaccines likely reach maximum protection from 14 to 28 days after both shots, said Dr. Akiko Iwasaki, a professor of immunobiology at Yale University.

The endpoint protection from symptomatic infection was measured two weeks after the second shot for Moderna, and one week after second shot for Pfizer during the Phase 3 trials. That would be at 42 days for Moderna and 28 days for Pfizer.

That's not so different from Johnson & Johnson. After 28 days, its protection from severe disease was 85% and after 49 days it was 100%, said Iwasaki.

She did acknowledge there's no good head-to-head data.

"It is comparing apples and oranges though since the efficacy was measured differently, Moderna and Pfizer-BioNTech as symptomatic infections, Johnson & Johnson as moderate to severe disease," she said.

How well the vaccines work against newly emerging COVID-19 variants is another factor.

Scientists say it's difficult to really know whether any of the three work better against the variants as the vaccines were tested at different times when different variants were circulating.

Even so, some Americans prefer Johnson & Johnson.

"If I could choose, I would go with Johnson & Johnson. The reason why is because this vaccine protects people from the variants. Pfizer-BioNTech and Moderna came out before the variants showed up," said James Bock of Rockford, Illinois.

Side effects: Fever, chills and fatigue

All three COVID-19 vaccines in use in the United States can cause short-term side effects in some people, including pain at the injection site, fatigue, headache, muscle pain and joint pain.

These are a sign the immune system is kicking into high gear and not a bad thing — they don't mean the vaccines aren't safe.

For Pfizer-BioNTech and Moderna, more than half of people who get them have chills and fever a few days afterward. If you haven't had COVID-19, the reaction tends to be stronger after the second dose, said Vanderbilt's Edwards.

"If you've had COVID before, you'll get sicker with the first dose and less with the second," she said.

These differences could matter for some people. For example, younger people tend to have stronger side effects because their immune systems overall are stronger.

"If I'm an older person, then maybe I'm not going to need a couple of days off work if I get one of the shots, so Pfizer-BioNTech or Moderna are fine," said Bastian.

A younger person, or someone for whom taking a day of work is difficult, might prefer the Johnson & Johnson vaccine, she said.

For people who aren't thrilled with the idea of vaccines overall, Johnson & Johnson could be preferable because it's just one shot.

"They might say, 'That's not too much to ask. I'll do that,'" Bastian said.

Anaphylaxis: 4.5 cases per 1M doses

For the Pfizer-BioNTech and Moderna vaccines, there are reports of a small number of people experiencing anaphylaxis, an immediate, severe allergic reaction that requires a dose of epinephrine to stop. The average rate was 4.5 cases per million administered doses.

This is why people getting these vaccines are required to wait 15 minutes before leaving, where medical personnel are on hand to treat them.

Johnson & Johnson appears to have a lower rate of these reactions, though that could also be because it's newer and hasn't been given to as many people.

"We don't know what will happen when it's millions of doses of Johnson & Johnson" given, said Dr. Gregory Poland, director, Mayo Clinic's Vaccine Research Group, and editor-in-chief of the journal Vaccine.

Among those who had the severe reaction, one-third had a previous history of anaphylaxis and three-quarters had a known allergy to one of the components of the vaccine, said Edwards.

"The important thing to know is that no one has died from these reactions," she said.

For the very few people who have an anaphylactic reaction to their first dose of COVID-19 vaccine, experts are discussing whether they should get the Johnson & Johnson vaccine as their second dose, said Dr. Buddy Creech, director of Vanderbilt's Vaccine Research Program.

"If there is concern about allergy, you might want to have a conversation with your health care provider about getting Johnson & Johnson for your second shot," Creech said.

Take the vaccine available to you

In general, say experts, the vaccine you can get is the best vaccine for you.

That's how Paula Musich, in Ashland, Oregon, sees it. She'll be happy with whatever's on offer.

"I called today and there weren't even appointments. I don't think they'll be giving us a choice any time soon," she said.

But if offered the choice, which should you get? Here are some considerations

If getting the vaccine is difficult for you for whatever reason, the one-and-done Johnson & Johnson vaccine might be preferable.
If you want belt-and-suspenders maximum protection, then Pfizer-BioNTech and Moderna might be your choice.
If you know you're prone to severe allergic reactions, you might choose Johnson & Johnson, though the chance of anything happening is very tiny and medical personnel are there to deal with it.

One final thing: Whichever you get, there are probably more COVID-19 vaccines in your future. Many scientists think it's likely booster shots will be required, though whether yearly or every few years isn't known. COVID isn't done with us and we're not yet done with COVID.

Mike Cascone in Sunnyvale, California, likes that plan. Half-jokingly, he said, "I tell my friends, I want one of each. Then I'll be totally covered."