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While the world awaits the results of large clinical trials of Covid-19 vaccines, experts say the data so far suggest one important possibility: The vaccines may carry a bit of a kick.

In vaccine parlance, they appear to be “reactogenic,” meaning they have induced short-term discomfort in a percentage of the people who have received them in clinical trials. This kind of discomfort includes headache, sore arms, fatigue, chills, and fever.


As long as the side effects of eventual Covid-19 vaccines are transient and not severe, these would not be sources of alarm — in fact, they may be signals of an immune system lurching into gear. It’s a simple fact that some vaccines are more unpleasant to take than others. Think about the pain of a tetanus shot, for instance.

But experts say it makes sense to prepare people now for the possibility that Covid-19 vaccines may be reactogenic.

“I think one of the things we’re going to have to realize is that all of these vaccines are going to be reactogenic…. They’re all going to be associated with reactions,” said Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.


“I think if you were to point out that, look, this is going to be a little bit painful, but there’s an end to it, and there’s a greater good to be gained here, I think that that’s probably worthwhile,” agreed Brian Southwell, senior director of the science in the public sphere program at the Center for Communication Science at RTI International, a think tank located in Research Triangle Park, N.C.

At least two manufacturers, Cambridge, Mass.-based Moderna and CanSino, a Chinese vaccine maker, stopped testing the highest doses of their Covid-19 vaccines because of the number of severe adverse events recorded among participants in their clinical trials.

Ian Haydon, one of the volunteers who received the highest dose in the Moderna Phase 1 clinical trial, ended up seeking medical care after he spiked a fever of 103 Fahrenheit 12 hours after getting a second dose of the vaccine. (Most Covid-19 vaccines will likely require two doses to work.)

The side effects are being seen across a number of different vaccines, made in different ways. This does not appear to be a problem linked to a specific type of Covid-19 vaccine.

The Oxford University-AstraZeneca vaccine, which uses a harmless-to-humans virus that infects chimpanzees as its backbone, saw adverse events reported by 60% of recipients in its early phase trial, reported last week in the journal The Lancet. Half of patients who got the highest dose of the Pfizer-BioNTech vaccine — which like Moderna’s is a messenger RNA vaccine — reported side effects.

Even after abandoning study of its highest dose, CanSino saw nearly three-quarters of the people in the vaccine arms in its Phase 2 trial report side effects, though none was severe. The CanSino vaccine uses a human adenovirus as its backbone.

Getting people prepared for the fact that the Covid-19 vaccines may be reactogenic lets them know what to expect when vaccine becomes available, said Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland School of Medicine.

“As with many vaccines, we have found that if we let people know what to expect, then they have fewer concerns if side effects happen,” Neuzil said.

There’s plenty of evidence that people will accept reactogenic vaccines — will virtually rush to get them — if they are concerned enough about the condition the vaccine is designed to prevent.

Edwards said GSK’s shingles vaccine, Shingrix, which reportedly makes people feel pretty miserable for a short period after injection, is a perfect example. Despite the possibility of discomfort, from the moment the vaccine was brought to market, the company could not keep up with the crush of demand for it. (GSK recently announced the vaccine was no longer in short supply.)

Most people know someone who has had shingles; they’ve heard how painful the condition — a reactivation of latent varicella virus, a late side-effect of chickenpox infection — is for people who develop it.

But the behavior of many Americans suggests they don’t see Covid-19 as a particular threat, with many resisting wearing masks and following the social distancing recommendations that have successfully driven down transmission in a number of other parts of the world.

A variety of polls suggest between half and 70% of Americans plan to be vaccinated when Covid-19 vaccines become available, figures that raise concerns in some quarters about the ability of vaccines to trigger herd immunity in the U.S. population.

Noel Brewer, a professor of health behavior at the University of North Carolina, isn’t worried at this point about those polling numbers. At present, it’s not even clear if vaccines will work, he said, which means pollsters are asking people about hypothetical decisions they may have to make at some unknown point in the future.

“It’s all just a bunch of question marks,” said Brewer, who actually thinks the polling numbers look pretty good under the circumstances. “Once folks are faced with a specific vaccine and a particular effectiveness profile and so on, they can then make a decision based on a thing, as opposed to an idea of a thing.”

For most people right now, Covid-19 is invisible “unless you are in an ICU,” he said. “For most of us every day, we don’t see people who are really sick.”

Brewer, who is on a World Health Organization subcommittee on Covid-19 vaccine safety, said people do expect some discomfort from getting vaccinated.

“The real question is: How much discomfort compared to what other things they may be facing? So, if you’re 70 years old and you can’t leave your house at all, you’re going to have one calculus as compared to if you’re someone who’s 20 years old,” he said.

Conditions at the time vaccine becomes ready for use will be a big influencing factor when the public is offered vaccines, said Southwell. In the meantime, though, he thinks it is critical to communicate with the public about issues like how vaccines are made and that the Covid-19 vaccines may be reactogenic.

People are paying attention to these issues, he said, arguing that members of public has a greater capacity to understand than they are generally given credit for.

“There might be a much greater case for acceptance if we do our work in building trust now and laying the groundwork now,” said Southwell. “But we’re not necessarily as focused on that as we could be.”

  • Most vaccines cause a reaction, so IMO a Covid vaccine reaction should not be hyped up. The phase 3 trial (if done with all possible back-ground info of each participant, including pre-existing conditions AND what vaccinations already had and when) will show whether there are any serious worries. The frantic speed of pushing through a vaccine will however leave unknown how long immunity lasts (in years, not just mere months), and if there are any detrimental long-term ramifications. People can chose to wait and see what happens with the many vaccinated over time – while however running the risk of catching Covid. Due to the development speed, this will be a dilemma for many. I am likely waiting for Inovio’s DNA based vaccine, and its Cellectra cell-stimulating injectors. What I feel is lagging is R&D on Covid treatments, because until there is a good vaccine, people are still dying – and that is an embarassingly horrendously high number in the US.

  • Maybe consider a side dose of morphine to provide a euphoric high to those who are hesitant about the vaccine. Word of mouth would be more like…”You’ve got to get that shot Bro!”

  • this is rubbish. ALL vaccines have side effects. Go to the manufacturer insert for each drug and find the truth and stop listening to the doctors who are paid by big pharma

  • This begs the basic question: If the virus has an asymptomatic/mild infection rate of about 80%, then it will be difficult to demonstrate clinical efficacy.

    The second question: 30,000 are needed for a sufficiently powered study. What constitutes a naive immunological state?
    We know that a larger number infected with the virus are negative by at least one antibody test, but may show a T cell response. But it is not clear if the T cell response is to the corona virus in general or COVID-19 in particular.

    Practically speaking, even mild reactogenic state (a nice euphemism for transient sickness) will be a deterrent for widespread adoption of the vaccine by the general population. If the vaccination is given while the patient has active disease will it precipitate adult respiratory distress syndrome (as it does in macaque monkeys)? If a severe reaction results, it will be a super strong deterrent because it violates the Hippocratic oath of “first, do no harm”.

    The next question: if the vaccine needs to be given annually, will the next inoculation cause more severe reactions than the first round of vaccination.

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