How do adverse event profiles of mRNA versus protein boosters influence emergency department visits?
Executive summary
mRNA boosters produce stronger antibody responses but also consistently show higher reactogenicity and a higher incidence of certain serious adverse events (notably myocarditis/pericarditis) compared with protein‑based boosters; studies and reviews link greater reactogenicity to more health‑seeking behavior, which can increase emergency department (ED) visits after vaccination (see comparative safety and reactogenicity findings) [1] [2] [3]. Public health monitors conclude most adverse events are mild-to-moderate and that vaccine‑related ED burden is small relative to health impacts from COVID‑19 itself [4] [5].
1. mRNA versus protein boosters: stronger immunity, stronger reactions
Randomized trials and reviews report that intramuscular mRNA boosters elicit higher neutralizing antibody titers and distinct memory B‑cell responses than non‑mRNA boosters, but come with a higher incidence of adverse reactions and greater reactogenicity [1] [2]. Multiple studies and clinical comparisons find protein subunit boosters (e.g., Novavax/NVX‑CoV2373) generally cause fewer and milder solicited adverse events while producing lower peak antibody responses compared with mRNA boosters [3] [6].
2. Which adverse events most drive ED visits after boosters?
Available sources emphasize injection site pain, fatigue, headache and myalgia as the most common symptoms for all platforms; myocarditis and pericarditis are rare but disproportionately reported after mRNA vaccination and are the type of serious event most likely to prompt ED evaluation [7] [8] [2]. Surveillance reports reviewed by CDC concluded adverse events after bivalent mRNA boosters were consistent with prior boosters and less frequent and severe than COVID‑19 illness itself, but they explicitly searched for myocarditis signals because such cardiac events are clinically significant and prompt ED care [4].
3. How reactogenicity translates into ED utilization
Higher reactogenicity raises the likelihood that vaccine recipients will seek urgent care even when events are short‑lived. Clinical trials and observational reports show mRNA boosters produce more intense short‑term symptoms and more Grade‑3 reactions, which likely increase ED or urgent clinic visits compared with protein boosters, which more often report only mild‑to‑moderate events [1] [2] [6]. Systematic surveillance studies stress, however, that the absolute rates of serious, vaccine‑related ED‑level events remain low and that routine monitoring attributes most common post‑vaccine complaints to transient reactogenicity rather than lasting harm [4] [9].
4. Tradeoffs: fewer ED visits versus less immunogenicity
The choice between platforms reflects a clear tradeoff: protein boosters may reduce immediate post‑vaccination health‑care visits because they induce less reactogenicity, but they often yield lower neutralizing antibodies and higher short‑term breakthrough infection rates in some studies—outcomes that can themselves increase later ED visits from COVID illness [3] [1]. Journal‑level RCTs and comparative analyses frame this as a balance between short‑term tolerability and peak immune response [2] [3].
5. Population and context matter: individual risk, prior infection, age and surveillance
Risk of myocarditis after mRNA boosters concentrates in younger males; older adults and people who had severe prior vaccine reactions are explicitly identified as candidates for protein alternatives in guidance and Q&As [8] [10]. Surveillance systems (v‑safe, VAERS, EudraVigilance) report context‑dependent signals and caution that epidemiology of adverse events shifts with circulating variants, background infection rates and vaccine uptake—factors that affect both the number and nature of ED presentations [4] [9].
6. What the data do not settle and key limitations
Available sources document comparative reactogenicity and rare serious events but do not provide a definitive, population‑wide count of ED visits attributable to each booster platform across the same time window; nor do they uniformly adjust for differences in who received which booster (age, comorbidity, prior infection) [1] [9]. Long‑term safety and the downstream impact of repeated boosting on immune function (e.g., IgG subclass shifts) are mentioned as open questions that could affect future ED utilization but remain incompletely characterized [2] [7].
7. Practical implications for clinicians and policymakers
Clinicians should counsel patients that mRNA boosters offer stronger immediate immune responses but carry higher short‑term reactogenicity and a very small increased risk of myocarditis, which can prompt ED evaluation; protein boosters are a reasonable alternative for people with prior severe mRNA reactions or specific risk‑benefit concerns [2] [10]. Public health messaging should continue to emphasize that most post‑booster events are transient and that the overall harms from COVID‑19 (hospitalization, death) are greater than observed vaccine‑related adverse events in surveillance reports [4] [5].
Limitations: this analysis relies on the supplied sources and their reported comparisons; available sources do not mention a single harmonized dataset that quantifies ED visits per booster type across identical populations and timeframes, so precise ED‑visit differentials cannot be calculated here [1] [4].