New York, NY—A new study gives pharmacists a way to turn complaints about mild side effects from COVID-19 vaccines into a positive.

The recipients often complain of local and systemic symptoms with SARS-CoV-2 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]).

A new study led by Columbia University Medical Center researchers sought to determine if those postvaccination symptoms are associated with improved vaccine-induced antibody response. To do that, they analyzed the association of self-reported postvaccination symptoms with anti-SARS-CoV-2 antibody response among Framingham Heart Study (FHS) participants contributing to the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study. The results were reported in the Journal of the American Medical Association Network Open.

In February 2021, participants in FHS—an ongoing, prospective cohort study evaluating cardiovascular disease risk factors—were invited to self-administer C4R questions on COVID-19 vaccination and associated symptoms and submitted a dried blood spot to test for anti-SARS-CoV-2 antibodies.

The report included participants who received two doses of mRNA vaccine at least 2 weeks before blood spot collection; postvaccination symptoms were categorized as systemic symptoms (e.g., fever, chills, muscle pain, nausea, vomiting, headache, and/or moderate to severe fatigue) or local symptoms (e.g., injection site pain and/or rash). The study team also measured immunoglobulin G antibodies to SARS-CoV-2 spike subunits.

Of the 3,200 FHS participants who were eligible to participate, 29% completed the C4R questionnaire and blood spot collection and reported two doses of BNT162b2 (414 [45%]) or mRNA-1273 (514 [55%]) vaccines. Only 9% of respondents, who had a mean age of 65 years with 61% women, reported previous COVID-19 infection. Nearly all (96%) were non-Hispanic white.

The results indicated that after either vaccine dose, 446 participants (48%) reported systemic symptoms, 109 (12%) reported local symptoms only, and 373 (40%) reported no symptoms.

“In bivariate analysis, symptoms were associated with younger age, female sex, prior infection, and the mRNA-1273 vaccine,” the authors advised. “Antibody reactivity was observed in 365 asymptomatic participants (98%), 108 participants (99%) with only local symptoms, and 444 participants (99%) with systemic symptoms (P = .08).”

The study concluded that in adjusted models, “systemic symptoms were associated with greater antibody response, although associations were attenuated with sequential adjustment for potential confounders. Similar results were obtained with exclusion of participants with prior COVID-19 infection.”

The researchers noted that their findings agree with a previous report in U.S. healthcare workers indicating higher postvaccination antibody measurements among those with significant symptoms after an mRNA vaccine.

No association was found, however, between symptoms after vaccination and race or ethnicity, BMI, or comorbidities.

“In this generalizable cohort, nearly all participants exhibited a positive antibody response to complete mRNA vaccine series,” the authors concluded. “Nonetheless, systemic symptoms remained associated with greater antibody response in multivariable-adjusted models, highlighting unexplained interpersonal variability. Further research on biological mechanisms underlying heterogeneity in vaccine response is needed.”

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