After months of waiting, we finally have detailed information on the safety and efficacy of the first Covid-19 vaccines that will be distributed in America.
On Thursday, a committee that advises the Food and Drug Administration voted to recommend the Moderna vaccine for an emergency use authorization for people ages 18 and over. Ahead of the decision, the agency shared the most comprehensive data to date on what we know about the shot. The same process happened last week with the Pfizer/BioNTech vaccine, which is now being rolled out across America following an EUA Friday night.
While both vaccines had already been shown to be highly effective, the new data provides a much more granular picture of their side effects and safety profiles.
People walk by the Pfizer headquarters in New York City on November 9.Kena Betancur/AFP via Getty Images
What’s now clear: An injection with either vaccine, both of which use mRNA technology, can feel more intense than other routine vaccinations (such as the flu shot) — with side effects for some recipients such as pain, headache, and fatigue. And this may be especially true for Moderna’s vaccine: About 16 percent of people who got the shot in clinical trials experienced a “severe” adverse reaction, a classification the FDA uses to refer to side effects that require medical attention and prevent people from going about their daily activities.
“We should anticipate that if you got vaccinated that day, you may not want to go to work,” Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College, said of the vaccines. That’s why health systems are being warned to stagger immunizing their workforces, to avoid “potential clustering of worker absenteeism,” as the vaccine expert group advising the Centers for Disease Control and Prevention (CDC) put it.
These side effects are known as reactogenicity, and vaccine developers and regulators allow for some level of reactogenicity in all approved vaccines. They can be a sign of the body’s immune response kicking into gear, said Saad Omer, director of the Yale Institute for Global Health.
I think it will be very important to communicate to the population that these vaccines have more reactogenicity (injection site pain, transient fatigue, headache, elev temp) than most other licensed vaccines. Not dangerous but unpleasant. People need to know what to expect. https://t.co/51R1J8vRKQ
— Florian Krammer (@florian_krammer) December 2, 2020
“Think about [reactogenicity] as mouthwash — it’s hurting while it’s working,” Omer said. “The key is to prepare people to know this will happen — this may hurt a little, give you a bit of fever — but these are short-term, known side effects that you need to be aware of.”
The stakes for clearly communicating information about each vaccine’s risks and benefits are high: More than a quarter of Americans reported that they would probably or definitely refuse to take a Covid-19 vaccine, according to a late-summer survey by the Kaiser Family Foundation, even if it were freely available and deemed safe by regulators. And with the virus spreading farther and faster in America than just about anywhere else in the world, it’s critical that people don’t feel caught off guard by the side effects or spread misinformation about the vaccine.
To achieve that, transparency is key, said Brendan Nyhan, a Dartmouth professor of political science who has been thinking about how to build confidence in the Covid-19 vaccines. “Millions of people are going to get this vaccine, and we know huge numbers of people are going to have normal side effects, which are often indicating that the vaccine is working. We want to build trust with people so there are no surprises when that happens.”
In that spirit, here’s what we know about the side effects of these two shots and how to think about them.
What mild and moderate side effects really mean
Before we get into the weeds, it’s helpful to understand how these companies classify side effects in the first place. In general, vaccine developers seeking approval in the US market use the FDA’s “toxicity assessment scale” to grade side effects and other adverse events from 1 to 4, from mild and moderate to severe and life-threatening.
Grade 1 “mild” side effects are generally easily tolerated and don’t interfere with a person’s regular activities. Grade 2 “moderate” effects may interfere with regular activities, grade 3 “severe” effects are incapacitating and need medical attention, and grade 4 are “potentially life-threatening,” usually requiring an emergency room visit or hospitalization. Let’s use the example of headache following vaccination. Here’s how the FDA would classify it:
- Mild: “No interference with activity”
- Moderate: “Repeated use of nonnarcotic pain reliever > 24 hours or some interference with activity”
- Severe: “Any use of narcotic pain reliever or prevents daily activity”
- Potentially life-threatening: “ER visit or hospitalization”
So a mild side effect is one you’d notice but doesn’t require any special care or keep you from living your life; a moderate side effect can keep you home from work but doesn’t warrant medical intervention; severe adverse events require medical care and definitely interfere with your normal life; and potentially life-threatening is just what it sounds like and usually involves a visit to or stay in the hospital.
In vaccine studies, these events are broken down into “local” reactions (meaning they’re specific to one part of the body, like pain or tenderness where the vaccine is injected) and “systemic,” whole-body reactions (like fever or fatigue).
For a vaccine to win FDA approval, any reactions people have during clinical trials have to be mostly mild and moderate. And that’s because the safety bar for vaccines is really high, even compared to medicines.
Moderna Covid-19 vaccine files kept at a research center in Hollywood, Florida.Chandan Khanna/AFP via Getty Images
Vaccines “are given to healthy people who have in many cases absolutely nothing wrong with them. And we are talking about [giving them] to literally billions of people. Even rare side effects if they’re serious matter enormously,” said Charles Weijer, a professor of medicine and an ethicist at Western University in Alberta, Canada. “We’re more willing to accept adverse effects [with drugs], provided those are counterbalanced by benefits to the patient.”
Mostly mild and moderate side effects are the safety profiles of both the Moderna and Pfizer/BioNTech vaccines — and that’s why the FDA in the US and drug regulators in other countries around the world are rushing to bring them to market. But there are important differences between the two vaccines.
What we know about Moderna and Pfizer/BioNTech side effects
Now let’s look at the best data we’ve got on the vaccines. It comes from the FDA’s analyses of phase 2 and 3 clinical trials ahead of their emergency use authorization meetings on December 10 for Pfizer/BioNTech and December 17 for Moderna. (The companies also released their own data for the meeting, but we focused on the agency’s independent reviews here.)
The reviews show the vaccines are both safe and that they’re extremely good at preventing Covid-19 infections (with around a 95 percent efficacy rate). That’s hugely important at a time when more than 3,000 Americans are dying from Covid-19 each day on average.
They also give a sense of what side effects we might expect when these vaccines are rolled out. The Pfizer/BioNTech vaccine caused mild or moderate reactions in most people, and severe reactions were rare. Moderna didn’t share the details of its vaccine trial’s mild and moderate side effects, but the FDA said mild and moderate is how they’d characterize the bulk of them. A key difference with the Moderna vaccine, however, is that we know severe reactions were more common in the trials.
Let’s get into what this means, but with a couple of caveats first. Because we have no head-to-head study of the two vaccines and the companies haven’t reported side effect data in the same way, doing apples-to-apples comparisons is tricky, said Hilda Bastian, an expert in reading medical evidence who has been analyzing the coronavirus vaccine data. The vaccines also come in different doses: 30µg in the case of Pfizer/BioNTech and 100µg with Moderna. While they’re supposed to be delivered in two shots per person, the time intervals are different: The Pfizer/BioNTech shots are three weeks apart, and Moderna’s are four weeks.
Pfizer/BioNTech and Moderna also tested their products on different populations. “Some of the differences affect risks and so could be affecting outcomes,” said Bastian. For example, there were more people of Hispanic/Latino background and with chronic lung disease in the Pfizer/BioNTech trial than the Moderna trial, she added. And in the real world, when the vaccines roll out to millions, the side effects may again look different.
With all that in mind, here’s what we know about each shot. For Pfizer/BioNTech the most common side effects overall, according to the FDA’s analysis of the data, were local reactions at the site of injection (including pain, redness, swelling), fatigue, headache, muscle pain, chills, joint pain, and fever. Again, these were mostly classified as mild or moderate. Severe reactions, meanwhile, were rare — occurring in 0 to 4.6 percent of participants, depending on the specific side effect.
In general, side effects popped up more after the second dose than the first. They also happened less frequently in people 55 and younger, the FDA said. You can see the breakdown of adverse events data in younger adults (18-55) in the chart below following dose 1 and, if you click through, following dose 2. (Note: Pfizer/BioNTech found no potentially life-threatening (grade 4) adverse reactions linked to the vaccine in the population they analyzed for safety.)
Now let’s look at the FDA’s Moderna data. Again, the company didn’t share the details of their mild and moderate adverse events — and revealed fewer details than Pfizer/BioNTech generally. But we know the most common reactions were injection site pain, fatigue, headache, muscle pain, joint pain, and chills.
Though the FDA said these were mostly mild and moderate, we only have the specific figures for total events and the more severe reactions. For example, 83 percent of study participants experienced a systemic adverse reaction of any level of severity while 15.7 percent experienced a severe “systemic” adverse reaction. Depending on the type, these severe events ranged in frequency from 0.2 to 9.7 percent.
Like the Pfizer/BioNTech shot, side effects were more frequent after the second dose and less common overall in adults 65 and older. Side effects that required hospitalization or emergency room visit were extremely rare. According to FDA analysis, “Across groups and doses, <0.1% reported a Grade 4 systemic reaction.” You can see that below, in a chart focusing on safety data in the younger adults in the study.
So what can we take away from all this?
“We know neither of these vaccines carries a high risk of serious adverse events. And we can expect them to cause typical reactions to vaccines,” said Bastian. But there are important differences. At least in these trials, all side effects and especially severe side effects were more common with the Moderna vaccine.
“The overall picture is that almost everyone has systemic adverse events with Moderna’s vaccine, and we don’t know how often they were only mild,” Bastian said. “For Pfizer/BioNTech, most people had at least mild reactions, but moderate reactions were common too.” So, at least for now, it seems reactions to the Pfizer/BioNTech vaccine “are considerably less severe.”
The vaccines “are on the fairly reactive side compared to most vaccines we commonly use,” said Jesse Goodman, a professor of medicine and infectious diseases at Georgetown University and a former FDA chief scientist. “It’s hard to compare between the two, but you do get the feeling these systemic reactions like muscle and joint aches are maybe more common in the Moderna vaccine than Pfizer.” Goodman also noted that rates of adverse reactions in Moderna’s placebo groups were higher, and side effects were generally less severe in people who had already been infected with Covid-19.
For the general population, though, there isn’t anything to fear with either vaccine. Again, side effects, if they do pop up, will be mostly moderate or mild. And this doesn’t come as a surprise to vaccine researchers. “The side effects [we’re seeing] are symptoms associated with products of the immune system — cytokines — that are recruited when fighting an infection or responding to a vaccine,” said Paul Offit, director of the Vaccine Education Center and professor of pediatrics at Children’s Hospital of Philadelphia. “That’s why people over 65 have a lesser rate of these side effects than younger people — just evidence of a more senescent immune system.”
There’s still a lot to learn about these vaccines
Even with all the available data, there are still unknowns about the two vaccines. We may not see additional rare side effects or severe reactions that will emerge until millions of people get them, for example.
Bell’s palsy, a form of temporary facial paralysis, showed up in three people who got the Moderna vaccine and four people who got the Pfizer/BioNTech shot in the companies’ late-stage trials. It’s not yet clear whether these cases are actually linked with the vaccines — since Bell’s palsy can occur in the general population irrespective of vaccination — but because “we see a similar imbalance in two different studies, it pricks my ears up a bit,” Goodman said, and it’s something we’ll learn more about as the vaccines are rolled out.
There are also groups the vaccines weren’t tested in, like pregnant women and people with HIV. In the cases of anaphylaxis in the UK following vaccination with the Pfizer/BioNTech shot, two people with a history of severe allergies — the kind that force them to carry around EpiPen-type devices — had a potentially life-threatening allergic reaction, were treated, and recovered. Allergic reactions were very rare in the Pfizer/BioNTech trial (affecting only 0.63 of people who got the vaccine, according to the FDA’s analysis). And people with severe allergies were also excluded from the study.
Clinical trials are not the real world of people; they all have inclusion/exclusion criteria.
Like no history of anaphylaxis (protocol ).
The same day @Pfizer vaccine rolled out, 2 cases of severe allergic reactions in healthcare workers.
There will be more safety issues ahead. pic.twitter.com/9SRrWyPPDu
— Eric Topol (@EricTopol) December 9, 2020
The CDC is now advising that people with a history of severe allergic reactions to vaccines can still get the Pfizer/BioNTech shot but should be counseled about the risks and be monitored for 30 minutes afterward, while those with an allergy to a specific vaccine ingredient shouldn’t get the shot.
Long-term Covid-19 vaccine side effects are “not really a thing”
But, again, there’s some reassurance to be taken here: Severe allergic reactions to vaccines are extremely rare generally. Most serious vaccine reactions — such as the rare neurological disorder Guillain-Barré syndrome — tend to happen within six weeks of getting immunized, said Colleen Kelley, associate professor of medicine at Emory University, who is also a principal investigator in the Moderna trial. And we already have more than six weeks of data on safety and side effects in the two shots.
“People worry about late or long-term side effects occurring a year or two later — that’s not really a thing with vaccination,” Kelley said.
Instead of taking a large dose of medication for many years, where a side effect may surface only after lots of exposure, with vaccines, Bastian said, you’re getting a small dose to stimulate an immune reaction once or a few times. So it makes sense that the longer-term risks aren’t a major problem.
Again, though, this doesn’t mean all coronavirus vaccines are entirely safe or that there’s not more to learn about these two. And as other Covid-19 vaccines hit the market, clarity and transparency about what we know will be paramount if we want people to trust and take the vaccines, Bastian said. “The evidence says treat people like adults. Tell people the truth. Anything else is manipulation and that’s a form of lying.”
Source by www.vox.com