In a paper published on Friday, researchers from Columbia University, the University of Vermont and Boston University said side effects such as tiredness and a high temperature could be signs that the vaccine has been effective.

Using survey data and blood samples from 928 American adults, the research team analyzed the relationship between self-reported postvaccination symptoms and antibody responses. The average age of the sample group was 65.

Dried blood spot samples were collected from participants in February 2021, the same month that respondents were invited to fill out questionnaires about their COVID vaccination history. Anyone taking part must have had their most recent vaccination at least two weeks before the blood samples were submitted.

All participants in the study had been vaccinated with two doses of either the Pfizer-BioNTech or the Moderna COVID vaccine, both of which use mRNA technology to prompt an immune response.

Almost half of the participants reported having “systemic symptoms”—like fever, chills, nausea, vomiting, headaches, or fatigue—after either dose of the vaccine. A further 12% said they had had local symptoms like a sore arm or rash near the injection site, and 40% reported no side effects at all.

Researchers found that postvaccination symptoms were associated with younger women, prior COVID infection, and the Moderna vaccine.

Scientists also measured the level of antibodies in the blood that work by targeting COVID-19’s spike protein.

Immune responses to the vaccines were observed in almost all of the participants, but greater antibody reactivity was seen in those who had reported either local or systemic postvaccination symptoms. Among those who had side effects after being vaccinated, 99% were found to have had an antibody response to immunization, compared to 98% of the nonsymptomatic cohort.

The paper’s authors noted that nearly all participants exhibited a positive antibody response to the vaccines, but said “nonetheless, systemic symptoms remained associated with greater antibody response in multivariable-adjusted models.”

They also acknowledged that their sample group being of older age and predominantly white limited the impact of their study, saying more research is needed.

However, they argued that their findings support “reframing postvaccination symptoms as signals of vaccine effectiveness.”

Side effects

While side effects from COVID-19 vaccines are fairly common, they vary from person to person. According to the U.S. Centers for Disease Control and Prevention (CDC), the most common side effects after a second shot or a booster are mild and include fever, a headache, fatigue, and pain at the site of the injection.

The two newly approved bivalent vaccines—manufactured by Pfizer-BioNTech and Moderna to specifically target both the original strain of COVID and fast-spreading Omicron subvariants—caused similar side effects to the original vaccines during human testing.

Although side effects from a vaccine are a sign that the immunization is working, doctors have said not experiencing any postvaccination symptoms does not mean there has been no immune response, and there is no major scientific evidence that those with more obvious side effects are better protected.

Last year, a study on the potential link between COVID vaccine side effects and immune response found that a lack of postvaccination symptoms “does not equate to lack of vaccine-induced antibodies.”