Coronavirus vaccines compared: What to know about shots from Moderna and Pfizer, from safety to side effects

Coronavirus vaccine canada — A nurse is inoculated with the Pfizer/BioNTech coronavirus vaccine.
REUTERS/Carlos Osorio

Both Moderna and Pfizer have FDA-authorized coronavirus vaccines, with data showing both are safe and effective at preventing COVID-19 infections.
But, the shots do have some subtle differences.
Moderna's might better protect against severe cases, while Pfizer's seems to have milder side effects.
Here's everything you need to know.
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US regulators greenlit a second coronavirus shot on Friday, authorizing Moderna's vaccine for emergency use.

The Food and Drug Administration granted emergency use authorization for Pfizer's two-shot vaccine on December 11. Both vaccines are very similar two-dose mRNA shot courses.

Late-stage clinical trials for both vaccines are ongoing, meaning more results could still come in and change what we've learned about how well these shots work.

But so far, the two vaccines appear quite similar, and they both seem to be safe and highly effective, based on trials that have been conducted on tens of thousands of people around the world. The trials compare people who got two doses of the Pfizer-BioNTech vaccine or of Moderna's vaccine to people who got fake shots known as placebos.

Here's what we know so far.

Both shots are overwhelmingly effective at preventing symptomatic cases of COVID-19

The primary goal of both vaccine studies was to see if the shots can prevent the symptomatic kind of COVID-19, where people exhibit outward symptoms of illness, such as coughing, fevers, and shortness of breath. Both vaccines did well at that task.

Pfizer: Pfizer's vaccine was 95% effective at preventing symptomatic disease, with the trial recording 162 COVID-19 cases in the placebo group and 8 in people who got the real vaccine. Pfizer's study began counting cases sooner than Moderna's, with researchers starting to count cases one week after people got the second (booster) dose.

Moderna: Moderna's shot was 94.1% effective at preventing symptomatic disease. The study tallied 196 COVID-19 cases among volunteers, with 185 in the placebo group and just 11 among those getting the experimental vaccine. This study started counting cases 14 days after people got their second shot.

The vaccines work really well at preventing the most severe COVID-19 infections, and deaths

People with severe cases of COVID-19 can end up hospitalized, paralyzed, or dead. Fortunately, both Pfizer and Moderna's shots seem to protect people very well from some of the most severe instances of disease, and no one who was vaccinated died from COVID-19 during these studies.

Pfizer: 8 fully vaccinated people (out of more than 18,100) in Pfizer's study got sick with COVID-19. One of those infections was severe, but none required hospitalization. Three placebo recipients also became severely ill, according to the study's final analysis. Two of those people were hospitalized, with one requiring intensive care.

Moderna: 11 fully vaccinated people (out of more than 13,900) in Moderna's study got sick with COVID-19. None of their infections were severe. In the unprotected control group, 30 severe infections were recorded during the study period, including one death.

Both vaccines dramatically reduced people's odds of developing severe infections, and eliminated deaths. Meanwhile in the US population at large, more than 300,000 have perished from this disease so far.

We don't know if either vaccine can prevent asymptomatic spread

Can these vaccines prevent infections altogether, including asymptomatic cases? Scientists don't know yet.

Dr. Peter Marks, a top FDA regulator, said on a December 14 livestream with JAMA that if he had a genie in a bottle, one of the first questions he would ask is whether these vaccines provide what's called sterilizing immunity, which prevents both symptomatic and asymptomatic infections.

Pfizer: Pfizer presented no data related to asymptomatic infections, viral shedding, or contagiousness as part of its application to the FDA. The agency said additional data is needed, "including data from clinical trials and from the vaccine's use post-authorization." Marks said he hopes findings in animal studies that shots seemed to halt viral shedding could translate to humans and reduce asymptomatic spread, "but we don't know for sure."

Moderna: Researchers swabbed volunteers for the virus before both injections. When volunteers came back for their booster shot, researchers found a handful of positive cases among people who didn't have symptoms: 14 positives among those getting Moderna's vaccine and 38 cases in the placebo group. While Moderna said that suggests "that some asymptomatic infections start to be prevented after the first dose," the FDA said the data is too limited to make any conclusions.

How long will protection last?

Durability of the protection from the vaccines is one of the biggest unknowns.

In both studies, participants were followed for at least two months after their shots, but beyond that timeframe, it's not yet clear how long the vaccine protection lasts. Will people need to get re-vaccinated in months, or years? No one knows yet if, or when, people will need to come back to doctor's offices for booster shots.

That's true for shots from both Pfizer and Moderna, though an analysis published on December 3 in The New England Journal of Medicine on recipients who got Moderna's shot as early as March showed only small decreases three months out in the level of neutralizing antibodies. Those are virus-fighting proteins that play a critical role in our immune response. As the study carries on and participants are followed for longer periods of time, we should get a better picture of if, or when, protection wanes.

Both shots have the side effects you'd expect from a vaccine. Moderna's may be more severe.

There's two buckets of side effects with vaccines: the expected and the unexpected. The expected ones are byproducts of the vaccine generating an immune response. Your body reacts to the shot, leading to temporary, usually mild, side effects like fatigue, headache, and chills. Here's how both vaccines stack up, and the rates of more severe reactions.

Pfizer: Compared to Moderna's shot, there were fewer reports of pain, fatigue, and headaches in Pfizer's vaccine trials. The most common side effects were injection site pain (84%), fatigue (63%), and headache (55%). Severe side effects after the second dose happened with less frequency than Moderna's trial, with the highest rates among volunteers under 55 years old: 5% recorded severe fatigue, 3% had severe headaches, 2% had severe chills, and 2% had new or worsened muscle pain.

Moderna: More than nine in 10 people registered some level of side effects, with most being mild or moderate. The most common reactions were injection site pain (92%), fatigue (69%), headache (63%), and muscle pain (60%). Younger participants recorded more side effects. Among volunteers ages 18-64, nearly 1 in 5 had a severe reaction after the second booster dose.

The most common severe side effects for this age group were fatigue (11%), muscle pain (10%), joint pain (6%), fever (2%), and chills (2%). Among this younger group, a handful also recorded grade-four side effects, which are potentially life-threatening in severity. Ten of these volunteers, less than 0.1%, had grade-four fevers, which exceeded 104 degrees Fahrenheit.

Pfizer's shot seems to be more effective for older adults, while Moderna's may be better at preventing severe cases

Both of these vaccines are recommended for adults of any age. But, the trials didn't have a uniform number of people of all ages in them, so it's still unclear which vaccine might work best at every age.

Pfizer: Vaccinated 4,294 people who were 65 years or older (about 21% of the vaccinated group). The oldest Pfizer vaccine recipient was 89 years old, and the average age of participants was 51. The vaccine appeared to work slightly better in people under 55 (96% effective, versus 94% in older adults), but those numbers could shift as more people get vaccinated, and the difference is not statistically significant.

Moderna: Vaccinated 3,527 people who were 65 years or older (about 25% of the vaccinated group). The oldest Moderna vaccine recipient was 95, and the average age of participants was 52. The vaccine appeared to work slightly better in people under 65 (86.4% effective, versus 95.6% in younger adults), but those numbers could shift too, as more people get shots. Moderna's shot also appeared to be gentler on older people, with more severe side effects like headaches and fatigue tending to fall on the younger vaccine takers, under 65. So far, Moderna's vaccine appears to be 100% effective at preventing severe cases (there was one severe case in the Pfizer trial.)

The diversity in the trials mirrored the real world

Historically, vaccine trials, and scientific research trials in general, have been pretty bad about leaving women and people of color out. But, Pfizer and Moderna have made some improvements to diversity in their coronavirus vaccination studies, which is important for a vaccine that's going to be delivered to hundreds of millions of people across the country, and around the world.

Pfizer: Pfizer's vaccine was tried in six countries: the US, Argentina, Brazil, Turkey, Germany, and South Africa. 49% of volunteers were women, 51% were men.

Most of the vaccine recipients were white, with the final breakdown as:

55% White
26% Hispanic/Latinx
10% Black/African-American
5% Asian
2.5% Multiethnic
1% Native American (includes Alaska Native, Native Hawaiian/Pacific Islander)
0.5% Other

Moderna: Moderna's vaccine was only tried out on participants in the US. 48% of volunteers were women, 52% were men.

Most of the vaccine recipients were white, with the final breakdown as:

64% White (compared to the 60% of the US population)
20% Hispanic/Latinx (19% of the US population)
10% Black/African-American (13% of the US population)
4% Asian (6% of the US population)
1% Native American (includes Alaska Native, Native Hawaiian/Pacific Islander) (1.5% of the US population)
<2% Other

Pregnant women were left out of the studies

Very few people were excluded from the vaccine trials, categorically, and plenty of participants had pre-existing conditions like diabetes, hypertension, obesity, liver disease, and heart issues. But, there were a few groups the trials left out.

Pfizer: Left out people younger than 16 (the study is now being expanded to include kids 12 and up), lactating and pregnant people (though, a few did get pregnant during the trials), and people with a prior, severe allergic reaction to a vaccine. There were immunocompromised patients allowed in the study, but not many of them. For example there was only one person in the study with HIV or AIDS, and they were in the control (placebo) group.

Moderna: Left out people younger than 18 (the study is now being expanded to include kids 12 and up). Enrolled mainly frontline workers (82% "at occupational risk" of contracting COVID-19, with 25% of them healthcare workers.) Pregnant people were also excluded from Moderna's study, and like Pfizer's trials, there were immunocompromised patients allowed in this study, but not many of them. Again, there was only one person in Moderna's study with HIV/AIDS, and they were in the control (placebo) group.

Neither shot has any major safety concerns, but regulators will be watching closely for cases of Bell's palsy and allergic reactions

Massive studies, enrolling tens of thousands of people, haven't identified major safety concerns for either vaccine. But public-health regulators around the world are on watch, particularly as these shots are rolled out to millions of members of the public. Here are some of the potential safety concerns they are watching closely.

Pfizer: Pfizer's massive trial had a handful of Bell's palsy cases, a condition of weakening facial muscles that is typically temporary. Four cases were reported in the vaccine arm, and none in the placebo group.

UK health regulators have warned against anyone with a history of severe allergies to food or medicine getting Pfizer's vaccine after two people with those allergies had non life-threatening allergic reactions to the shot. Three healthcare workers in Alaska have had similar allergic reactions after getting Pfizer's vaccine.

Moderna: Among more than 30,000 people who signed up for Moderna's study, four volunteers subsequently developed Bell's palsy. Three got Moderna's shot, and one got the placebo.

Combining the two trials, nearly 40,000 people got an experimental vaccine with seven developing Bell's palsy, a frequency of less than 0.1%. The numbers are far too small to tell if the cases are related to the vaccines or a product of random chance. The FDA said a relationship with the vaccine "cannot be ruled out" and should be monitored closely going forward.

No data on children yet, but testing is underway

Children won't be getting a coronavirus vaccine anytime soon, outside of clinical trials. US public-health leaders have said they hope there's enough pediatric data in 2021 to begin immunizing children in the summer. But that depends on the studies working out as hoped.

Pfizer: Pfizer began vaccinating kids as young as 12 in October, expanding its ongoing trial to recruit children. The FDA has already authorized Pfizer's shot for people 16 and older, despite its study having just one COVID-19 case among 16- and 17-year-olds. Agency scientists reckoned it was "biologically reasonable to extrapolate that effectiveness in ages 16 to 17 years would be similar to effectiveness in younger adults."

Moderna: Moderna dosed its first teenagers on December 10 in a study of children ages 12 to 17. CEO Stephane Bancel hopes to have results from this study, enrolling 3,000 healthy kids, by spring 2021. Moderna's emergency OK is only for adults over 18, for the time being.

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