Individuals who experienced side effects, including fevers, chills, or muscle pain, after Covid-19 vaccination typically had a greater antibody response than those who did not, according to a new study published in JAMA Network Open.

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Study details and key findings

For the study, researchers from Columbia University, the University of Vermont, and Boston University used survey data and blood samples from 928 adults to analyze the relationship between self-reported postvaccination side effects and antibody responses.

There were 360 male participants and 568 female participants. The mean age of the participants was 65 years, and 96% were non-Hispanic white. All participants had been vaccinated with two doses of either Pfizer-BioNTech's or Moderna's Covid-19 vaccines.

Systemic symptoms, such as fever, chills, nausea, vomiting, headaches, or fatigue were reported by 48% of participants following either vaccine dose. Twelve percent said they experienced only local symptoms, such as a sore arm or rash at the injection site, while 40% said they had no symptoms at all.

When measuring the antibody levels, the researchers found that an immune response was observed in almost all of the participants (99% in the symptomatic group and 98% in the asymptomatic group). However, multivariable-adjusted models showed that "systemic symptoms remained associated with greater antibody response," the researchers wrote.

Researchers found that participants in younger age groups, those who received a Moderna vaccine, and women were more likely to have a better antibody response.

However, the researchers also noted limitations to the study, including that most of its participants were white and in older age groups, and said more research was needed to fully understand the relationship between symptoms and vaccine effectiveness.

Commentary

According to the researchers, the study's findings "support reframing postvaccination symptoms as signals of vaccine effectiveness and reinforce guidelines for vaccine boosters in older adults."

However, experiencing no side effects after vaccination doesn't mean the vaccine isn't producing a robust immune response. Almost all participants in the study regardless of whether they had side effects still exhibited a positive antibody response after their Covid-19 vaccination.

"I don't want a patient to tell me that, 'Golly, I didn't get any reaction, my arm wasn't sore, I didn't have fever. The vaccine didn't work.' I don't want that conclusion to be out there," said William Schaffner, a professor in the division of infectious diseases at Vanderbilt University Medical Center and medical director of the National Foundation for Infectious Diseases, who was not involved in the study.

"This [study] is more to reassure people who have had a reaction that that's their immune system responding, actually in a rather good way, to the vaccine, even though it has caused them some discomfort," he said.

"A lot of people have speculated over the years whether people who had more of a reaction to the vaccine might actually have that represent a more vigorous immune response," Schaffner added. "And these data would appear to support that." (Howard, CNN, 10/24; Twenter, Becker's Hospital Review, 10/24; Taylor, Fortune, 10/25; Hermann et al., JAMA Network Open, 10/21)