An Analysis of SARS-CoV-2 Vaccine Reactogenicity: Variation by Type, Dose, and History, Severity, and Recency of Prior SARS-CoV-2 Infection

BACKGROUND: There is limited information on the functional consequences of coronavirus disease 2019 (COVID-19) vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care (“severe” side effects). METHODS: The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2789 adults who were vaccinated between December 2020 and December 2021. RESULTS: Severe side effects were most common with the Ad26.COV2.S (Janssen/Johnson and Johnson) vaccine, followed by mRNA-1273 (Moderna) then BNT162b2 (Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%; P < .001). First (but not second) dose side effects were more common in those with vs without prior severe acute respiratory syndrome coronavirus 2 infection (9% vs 2%; adjusted odds ratio [aOR], 5.84; 95% CI, 3.8–9.1), particularly if the prior illness was severe or critical (13% vs 2%; aOR, 10.57; 95% CI, 5.5–20.1) or resulted in inpatient care (17% vs 2%; aOR, 19.3; 95% CI, 5.1–72.5). Side effects were more common in women than men but not otherwise related to demographic factors. CONCLUSIONS: Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19—particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful postvaccine symptoms.