It’s good to feel bad after your COVID shot

Published October 12, 2023

8 min read

Jeremy Warner has had six shots of the COVID vaccines. He’s an oncologist at Brown University in Providence, Rhode Island, where he treats immunocompromised patients with cancer who are especially vulnerable to COVID-19. To keep his patients safe, Warner rolls up his sleeves as soon as the U.S. Food and Drug Administration recommends a new vaccine, but he dreads the aftermath. “Each time I’m like, oh my God, I can’t do this again!”

After each COVID shot Warner gets a fever, headaches, shaking chills, and painful, swollen joints along with the expected tenderness at the site of injection. “The worst was the second shot that lasted two or three days,” recalls Warner. “This recent round, maybe one or two days.”

The good news: new research shows that more side effects might be beneficial because they reflect greater production of virus-fighting antibodies after vaccination.

“The more symptoms people reported, the higher their antibody levels were,” says Aric Prather, a clinical psychologist at the University of California San Francisco, who led the study.

Fear of reactions make some people hesitant to get a COVID shot and a third of adults in one study blamed vaccine side effects for not taking the bivalent boosters last winter that targeted two strains—the original SARS-CoV-2 virus and an Omicron subvariant.

“[But] the side effects show the vaccine is working,” says Drew Weissman, an immunologist at the University of Pennsylvania, whose research led the development of the mRNA vaccines, including Moderna’s and Pfizer’s. Weissman and Katalin Karikó were recently awarded the 2023 Nobel Prize in Physiology or Medicine for their work on modifying mRNA. 

COVID-19 vaccines are overwhelmingly safe and effective. Fewer than 1 percent of the 10.1 million U.S. respondents who have completed health surveys through the Centers for Disease Control’s V-safe program—launched in December 2020—have reported needing a medical care after vaccination.

But mRNA vaccines are among the most painful of vaccines, comparable to the shingles vaccine. Scientists don’t yet know why. “There’s still a lot that’s being learned about the side effects of mRNA vaccines,” says Deborah Fuller, a vaccinologist at University of Washington School of Medicine, Seattle. Fuller is attempting to develop next generation of nucleic acid vaccines and hopes they will be better tolerated.

Side effects after jab indicate high antibody levels 

During COVID-19 vaccine trials, between 50 and 90 percent of participants reported chills, fatigue, headache, and malaise, and more than 30 percent of vaccinated people experience some discomfort.

About 70 percent of V-safe respondents reported pain at the injection site; fatigue was the most common side effect in the first week after receiving the vaccine.

Prather wanted to know whether psychological, behavioral, or biological symptoms could predict the vaccine response. To address the question, he recruited 364 adults to donate blood samples before their first dose of a COVID vaccine, and then again donate samples one and six months after getting two doses of an mRNA vaccines. Prather and his colleagues measured the level of antibodies in volunteers’ blood; not just the ones that react with the spike protein used in the vaccine, but also the “neutralizing antibodies” that suppress the original SARS-CoV-2 virus.

The scientists compared the levels of antibodies against the volunteers’ self-reported symptoms—such as chills, feeling tired, feeling unwell, headache, pain at the injection site—over seven days. They found that when the worst symptoms occured after the second shot it was associated with higher antibody levels.

Though the symptoms may be unpleasant, our data and other studies provide evidence that your immune system is doing what it needs to do, says Prather. “That’s a good thing.”

Although the new study is not yet peer reviewed, it is consistent with previous research.

“Generally speaking, if you develop more symptoms, you have a better antibody response,” says Kevin Dieckhaus, an infectious diseases specialist at UConn Health, in Farmington, Connecticut. Dieckhaus’s own research has shown that people who experience COVID-19 vaccine-associated symptoms develop longer lasting immunity.

Mild to moderate symptoms after the flu vaccine also lead to reduced hospitalizations or death. “Our study suggests that some adverse reactions can be viewed as a good sign of the body’s appropriate response to COVID vaccines as well,” says Orly Vardeny, a clinical pharmacist researcher at the University of Minnesota Medical School who led the influenza vaccine study but was not involved with the latest COVID-19 research.

Studies also show that compared to those who only have localized pain or itchiness around the injection site, people reporting symptoms all over the body (fever, chills, muscle pain, nausea, vomiting, headache, and/or moderate to severe fatigue) generate greater antibody response.

Measuring post vaccine discomfort 

In the new study, unlike previous ones that only relied on self-reporting of symptoms—which can vary because of individual perceptions of symptom intensity—some participants wore a digital ring for about two months during which they got their COVID jabs. This wearable device measures heart and breathing rate, and body temperature, indicators of sleep patterns and stress. Skin temperature and heart rate increases predicted antibody levels following the second but not the first vaccine dose.

“The symptoms add up, and more symptoms in response to the vaccines seem to be associated with the greater durability of neutralization antibody levels,” says Prather.

However, researchers warn that the study doesn’t imply that people without symptoms are not protected.

“In fact, there were lots of people that reported low symptoms or no symptoms and had high neutralizing antibody titers,” says Prather. An earlier research has shown that 98 percent of people who had mild to no symptoms at all after vaccination still produced sufficient antibodies, compared with 99 percent of those who had more severe symptoms.

While milder symptoms may be associated with lesser mobilization of immune system upon vaccination, and potentially lower levels of anti-SARS-CoV-2 antibodies, this does not mean that the vaccine response is going to be less effective or less protective against viral disease, says Florian Douam, an immunologist at Boston University Chobanian & Avedisian School of Medicine.

It is also unclear if the relationship between symptom intensity and antibody response would be same for subsequent doses, and for more current variants. “Because people are experiencing the same sort of symptoms, perhaps these patterns would also be true as people get boosters,” Prather speculates.

It’s not yet clear why some people get different levels of antibodies after a specific vaccination, or why some develop more adverse effects such as more pain or more fever. It is also not clear why some can develop sufficient protection, even without developing the bad symptoms, says Alexander Ploss, an infectious disease biologist and virologist at Princeton University.

Factors such as age, gender, and if someone has ongoing infection or disease, may play a role in affecting the symptom intensity, Douam says.

Ploss and Douam have shown that some “protection-defining genes” affect why some people get sicker than others from COVID-19. In the event of a real infection, these genes ensure a rapid mobilization of multiple arms of the immune system to help control and clear infection, says Douam. But whether these genes could be involved in how people respond differently to vaccines is not yet known.

Despite a possibility of uncomfortable symptoms, scientists emphasize people should not be afraid of vaccines. But if someone gets very serious symptoms after getting vaccine, they must seek medical advice, cautions Prather.

“The risks of contracting COVID, or potentially a much more severe illness is probably far worse than the unpleasant symptoms that people experience when they get a vaccination,” says Prather.

While Warner, the oncologist at Brown University, loathes getting each COVID shot he emphasizes, “It’s not just for me, but also for my patients and loved ones who I come in contact with.”

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