At the beginning of a pandemic, conversations about the coronavirus vaccine were centered around speed. Now, we're on the brink of one of the fastest vaccine development timelines ever, and there's a pressing question yet to be addressed:
What will it actually feel like to get that shot?
Inverse asked readers what confuses them most about the coronavirus pandemic. Over 1,000 people wrote in. Now we're answering those questions with reporting and expert insight.
In an Inverse survey, 1,031 people responded to the question: "When it comes to vaccines, what question do you think the public should know most about?" The leading question, representing 38.4 percent of respondents, was "What are the side-effects?"
That curiosity is normal, William Schaffner, an infectious diseases specialist at Vanderbilt University Medical Center, tells Inverse.
Still, he explains, it's too early to know for sure what side effects will arise, if any — though there are some early indicators. There are currently nine coronavirus vaccine candidates in Phase 3 clinical trials, the third and largest stage of human testing. These ensure that by the time a vaccine is available, it has already been tested for safety and efficacy in thousands of people.
When we do have more robust data, it's essential that scientists, and people, feel comfortable talking about the results, Schaffner says. Neither group should shy away from asking hard questions about what we already know, what we might expect, and where the limits are of what the science can tell us at this stage.
"We have to do this with particular care and transparency and clarity," Schaffner says.
Expected Covid-19 vaccine side-effects:
Most vaccines come with some kind of known side-effect. These are not cause for alarm.
For example, the flu vaccine is sometimes accompanied with swelling at the injection site, fever, or muscle aches. For the shingles vaccine, these side-effects are particularly noticeable. Schaffner calls it "more of an 'ouchie' vaccine."
Results from earlier trials of coronavirus vaccines can show us early glimpses of these side-effects.
A combined Phase 1/2 trial of AstraZeneca's AZD1222 (formerly known as "The Oxford Vaccine") showed six side-effects were more common among the 543 people who received the coronavirus vaccine compared to those that received a meningococcal vaccine:
- Muscle ache
Fifty-six trial participants were given paracetamol (Tylenol) after being vaccinated, which appeared to diminish the side effects.
A Phase 1 trial of Moderna Inc's vaccine, which included 45 people, found that more than half of people experienced fatigue, chills, headache, myalgia (muscle ache), and pain at the injection site. One patient who received a higher dose of vaccine had a fever of about 103 degrees Fahrenheit and was eventually treated at an urgent care center. The participant also experienced mild fatigue that continued to last through day 6 post-vaccination.
Side-effects may be described as "mild" in press releases. Perhaps a better word is that they're expected, explains Naor Bar-Zeev, an associate professor at Johns Hopkins Bloomberg School of Public Health.
"So-called mild adverse events are still important," he tells Inverse.
For the elderly in particular, pain, fever, or muscle aches can compound existing pain from other conditions, or make life just a little bit harder. They're not something to write-off.
"If I suffer anyway because of arthritis or I have difficulty moving my shoulder, and then I get a vaccine and it gives me pain in my arm, fever, or leaves me feeling unwell for a few days, I have to make sure that I have enough shopping at home, I have enough food," Bar-Zeev explains.
"They have to set up systems that deliver vaccines to the elderly, and to everybody in a way that addresses their other needs."
As long as the side effects are made clear upfront, and systems are set up to help people deal with those "mild" events, these issues don't have to stop people from getting a vaccine (or a booster shot, if it's required) — provided it is safe and effective.
"We know we can do this," Schaffner says. He uses the shingles vaccine as an example. Despite the pain, about 80 percent of people return for the second shot, he says.
"The reason they do so is that whenever you get the shingles vaccine, it's communicated very clearly that you're going to have some side effects."
The potential for unexpected side effects – That said, some people are more worried about unexpected or severe adverse events that may arise. In a USA Today poll, 67 percent of 1,000 respondents indicated they wouldn't get a vaccine until someone else had tried it first.
Here, the coronavirus vaccine conversation gets more complicated.
Most vaccines, like the measles vaccine, have been received by millions of people over time (the measles vaccine has existed since the 1960s). Though adverse events can happen, scientists have a large enough dataset to understand just how rare they are, explains Bar-Zeev.
The coronavirus vaccine is still at the beginning of its lifetime. It starts with the standard vaccine testing process.
But before the vaccine is licensed — and the average person can go get one — tens of thousands of people will have received it. Both AstraZeneca's and Moderna's phase III clinical trials seek to enroll 30,000 participants. BioNTech's vaccine trial will enroll 44,000 participants.
"So far, the safety data are reassuring."
That's enough to catch rare or severe side effects that may not been seen in smaller trials that only enrolled a few thousand people.
Bar-Zeev does caution that those trials may not catch extremely rare events that could happen.
"At the end of those trials we will have about 120,000 people having received vaccine products, and half of those [who] have received placebos," he says. "If there's anything, like a rare event that happens in every one in 100,000 or one in 200,000, we won't know about it from those trials."
So far, there is evidence that systems already in place are poised to catch unexpected and potentially dangerous events.
A company statement to STAT indicates that this stoppage was "a routine action which has to happen whenever there is a potentially unexplained illness." The trial has since resumed in the United Kingdom, but not in the United States.
"So far, the safety data are reassuring," Bar-Zeev says.
"Even with these things are happening in the AstraZeneca trials [...] that's normal, and it's being examined. But then after that, we may find that there's something that you didn't expect. And if that is true, then we have to act accordingly."
For existing vaccines on the market, there are systems of post-licensing surveillance that can catch adverse events if they happen. In the US, reports can be submitted to the Vaccine Adverse Event Reporting System. Anyone can submit a report if they suspect an unexpected adverse event has happened because of a vaccine.
Like serious adverse events that may be reported in clinical trials (like AstraZeneca's), it takes time to prove that these post-licensing events are actually related to the vaccine in the first place, Schaffner adds.
"To be a little facetious, I get a vaccine in my arm, and a day later, I trip and fall and break my leg. Well, that's a serious adverse event," he says.
The Inverse analysis — Though we will likely have a solid idea of the vaccine's safety and efficacy thanks to Phase 3 clinical trials, we may continue to learn new things about it over the course of those trials and even beyond them.
Coronavirus vaccines will continue to change as more data becomes available. It is possible that we will have a licensed vaccine we don't know everything about when it hits the market.
That might feel unsettling but it's actually exactly what we should expect. If it feels as if we can't deliver perfect answers right away, it's not always cause for alarm. It's a reason to keep asking questions and demanding answers.
"There's a lot of unanswered questions, as people know, and people are right to be asking questions and being cautious, and demanding good quality data," Bar-Zeev says.