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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.”

  • Hi, I was just wondering why you didn’t mention that Inovio’s DNA vaccine was not “reactogenic” in Phase 1 participants, like these other vaccines…Inovio stated vaccine did not have anywhere near the adverse events as these other vaccines. Why leave out this important fact for readers? Thanks!

  • All vaccination has the effect of attenuated effect of virus. Small features thus develops that indicates the onset of vaccine effects, this mild sufferings helps to develop the antibody which gives us immunity. This sufferings are acceptable.

  • “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.
    Why would someone at 70 not be able to “leave their house at all”? Maybe someone who’d broken his spine and been confined to a wheelchair in an apartment with no elevator? Or a victim of severe MS, whose medication reduces her immunity too far to risk leaving home with another SARS about? I’m searching for a scenario that would explain this odd example, but I suspect the explanation is ageism. Does Prof. Brewer not have parents, mentors, colleagues, friends outside his immediate age group? Many people I know in their 70s have retired, and are leaving their houses or apartments more than the rest of us, now that they have time to do things besides work and sleep!

    • Because the older population are advised to stay at home since they are at higher risk.

      If I am 80 years old, my head would be fully geared up with PPE if I ever go out.

  • At 82 I have the following UNDERCONTROL situations: fibromyalgia, wide-spread arthritis, chronic sinusitius, high bloodpressure etc. normal states for most people my ago. I also take ppi’s, thryroid med, B/p meds, cholesterol meds. So far, the “mild symptoms” which can be expected are NOT considered mild to me. So many seniors in relatively good health do not need pain, nausea, diarhhea and a 103 fever. I had a shingles shot. I get regular flu shots. I get cortisone shots for inflammation. I NEVER experienced the side effects you “can expect” with proposed vaccine. I thought one of the concerns was hoping to get a vaccine so seniors could once again join society as worthwhile humans. Perhaps I misunderstood.

    • Not whole aTrunp is in office. We’d have to be stark raging crazy to place our lives in his hands. I’m a young senior with hbp, mitro valve prolapse, borderline diabetic. I will take my chances on nature and pray this country will one day be out back together. It’s seriously far from anything great we were thought our families had a sense of as security before trump, coronavirus, and the police brutality.

  • Few people will trust any vaccine that is released while Trump is in office. It is clear to most Americans that he doesn’t care whether they live or die and if getting a vaccine improves his chances for reelection then he will get a vaccine. No matter thr cost to human beings.

    Most people I know plan to wait six months even if it means they have to live the way we are living now –scared and isolated.

    We have only had ourselves to rely on during this lethal pandemic there is no functioning CDC no functioning government or president, and we are rarely allowed to hear from health experts so we will continue to rely on ourselves and be extremely cautious about vaccine.

    • You are so right to feel this way Anna. Trump stepped into office excusingvevery watchdog group and undoing everything that held us together. He divisively separates us, has races fighting against one another starting with his claim to need this Mexico border wall. Dear American people; Mexicans have no threat to us – as Trump will have you believe the drug lords and gangs (by the way, where are they right now with all this chaos) are a threat. Black people are no threat to America as they don’t have anything and have worked hard to build this country just like Mexicans. What is so silly is how China has come in while all focus is on Mexicans and blacks and bought up all the land and property, cstock and huge corporations, laughing all the way to the bank as they poison our foods with bio-chemicals “stupid Americans” is what they are saying. Where do you really think autism comes from? China has tons of kids tucked into orphanages with it and has had it for much longer from all the crap they do to the food supplies to mass produce garbage foods that rot our bodies and infect us with toxic preservatives and fake foods. Don’t believe it? Look at what Americans looked like in the 59s, 69s, 70s, even 80s and into 90s. Now we look and feel like crap since outsourcing our kitchen and farms to the enemy country China. Good grief they need to wake up!! Trump is bs saying he’s bringing manufacturing here. Trump and Melania’s merchandise is ‘Made in China”🤣🤣🤣 EVERYTHING at Walmart is produced by China pretty much – so folks are ok feeding their babies and families a meal prepared by your enemy country, but afraid for a black person to share a spot on the bus with? This administration created this chaos and has a master plan that is scary. Just my 2 cents

  • Why would anyone trust a vaccine that has been rushed to market? These biologics take years to be safety tested. We are not dealing with a simple pill here, we are talking about injecting substances that have not been tested on animals first. These types of vaccines (for SARS viruses) have never been able to be made safely so why now? In about 3 decades the scientists could not figure out a safe SARS vaccine and had to abandon the research due to the fact that the recipient, when challenged with the actual antigen, had extremely serious adverse reactions. I’m happy with the principle of vaccination but not with ‘fast tracking’ them and skipping vital safety testing.

    • The vaccines under development have all been tested on animals. They will not be given to humans until they have gone through phase 3 trials on 30,000 or so people. SARS vaccine was not abandoned due to adverse reactions, it was abandoned because the SARS virus itself disappeared.

    • Hi Kathleen – there are some inaccuracies in what you’re saying. These vaccines absolutely have been tested in animals, and they are being tested for safety in humans now. It’s also less than 20 years since SARS was discovered, so it can’t be three decades that they’ve been trying to make a vaccine for that. That research was paused because SARS went away, not because it was impossible.

  • As a scientist, I find it disturbing that other scientists think the public need to be subjected to a PR campaign to brainwash them into thinking a particular way about this vaccine. This is exactly why they don’t trust us.

    PR has no place in science. If this pandemic has highlighted anything, it is that the way science is currently conducted is not free from politics, self-aggrandizement, and hype. It really should be.

    • All mass vaccinations have required mass PR campaigns in the past. But the human race is much better off because PR campaigns to persuade people to vaccinate against polio, small pox, measles and influenza were done and succeeded.

    • In the Information Age, a void of valid scientific information will quickly be filled by lies and conspiracy theories. Believing that a public service campaign is unnecessary is naive and out of touch with realities of modern communication.

    • As a common US citizen who is less-well versed in the ins and outs of vaccine theory, I thank you. I research every vaccine and don’t take most of them. Too many side effects, by-products and an effective rate that doesn’t justify the means. I’m sure this vaccine will be no different, and will never take one.

  • How do you test the vaccine’s allergic reaction?. We know that a test dose is given in Penicillin injection. How this safety measure is taken in large scale vaccination?.Does the patient inform his existing diseases & allergic for specific medication. In such case how do you proceed further ?

    • An RNA vaccine cannot be thought of in the same way as a medication like an antiobiotic, at least in my opinion. Traditional vaccines introduce antigens into the body, while an RNA-based approach is only introducing RNA, which are like instructions for the creation of a specific antigen. I suppose a reaction is not impossible, but I highly doubt it would be common.

      The use of a chimpanzee adenovirus as a carrier is specifically done to prevent the immune system from attacking that carrier, because with a human adenovirus you run that risk of the immune system detecting it and labelling it a threat. However, before the current outbreak there was testing going on for hepatitis C vaccines that found nothing concerning.

      Regarding older people having a worse reaction to a vaccine, that is one of the questions the current phase III study of the Moderna vaccine will answer. And something that some people are overlooking is the fact that all of the serious reactions during the previous study, I think there were only 3 if I remember correctly, occurred at high dosages, and only after the second injection of the vaccine. Those dosages will not be used in the current trial. Also, the seriousness of the reactions are debatable. Sure the people probably felt lousy, but I highly doubt their lives were in danger. And just as importantly, these were short-lived reactions. We are not talking about it dragging out for the same duration as actually having the virus. And then there is not any of the damage to the circulatory system as you find with the virus. I think for the aged, the odds of surviving the virus are many many times worse than the vaccine. So the data of the last trial will answer the most important questions.

      And the last thing I want to point out that I feel is very important is the criticism over the speed of development. The RNA delivery technology had been developed before this virus first appeared in humans. There was absolutely nothing new, except the actual RNA instructions for making a specific protein. That is the beauty of these types of vaccines. The delivery method is the same, with only the instructions being different. Your body is what will make the protein that your immune system will attack, and again this is not something that is new.

      The speed of the trials is nothing to be concerned about either. Usually things take so long for many reasons, such as funding, the government red tape, along with the trials. But the red tape had been cut because of the pandemic, and money was no longer an issue. Also, recruiting for trials takes time, but with so many cases around the globe it was easier to find enough people to enroll. The main thing everyone should realize however is that the trials are still being done. The data is still there, and the speed of everything else means nothing compared to the data. If your rushing produced something that didn’t work, you wouldn’t even make it to the last phase of testing. There is absolutely no way that a vaccine will come to market in this instance if it does not work. The most important data will be gained during this last trial, and all of the questions we have will be answered.

      There will always be outliers to the rule, and if a large percentage of people have the potential for severe reactions even at smaller dosages, we will know and it will come into play regarding what happens next. I get a flu shot every year, and they make really fatigued. It usually lasts until I sleep and wake up again, about 8-12 hours, which is why I get the shot as late as possible in the evening. That doesn’t happen to most people, and that would be considered as having a reaction. Redness at the site of injection is considered as a reaction as well. So don’t freak out over that term either.

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