Abstract
BACKGROUND: Concern about side effects is a common reason for SARS-CoV-2 vaccine hesitancy. OBJECTIVE: To determine whether short-term side effects of SARS-CoV-2 messenger RNA (mRNA) vaccination are associated with subsequent neutralizing antibody (nAB) response. DESIGN: Prospective cohort study. SETTING: San Francisco Bay Area. PARTICIPANTS: Adults who had not been vaccinated against or exposed to SARS-CoV-2, who then received 2 doses of either BNT162b2 or mRNA-1273. MEASUREMENTS: Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose. RESULTS: 363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years [SD, 11.9]), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years [SD, 5.3]). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later. LIMITATIONS: The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown. CONCLUSION: Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake. PRIMARY FUNDING SOURCE: National Institute on Aging.