Abstract and Introduction
Objective: To assess the characteristics and associated disability of headache as an adverse event following vaccination.
Background: According to clinical trials and post-licensure surveillance, headache is a common symptom of vaccines, yet systematic investigations of post-licensure reports of this adverse event are lacking.
Methods: This was a retrospective database analysis study. We searched the Vaccine Adverse Events Reporting System (VAERS) database completed from July 1990 to June 2020 (a 30-year period prior to the start of COVID-19 pandemic) to identify reports of headache. We evaluated epidemiological features, including event characteristics, patient demographics, and vaccine type.
Results: In those aged 3 years or older, headache was the fifth most reported adverse symptom, present in 8.1% (43,218/536,120) of all reports. Of headache reports, 96.3% (41,635/43,218) included the code "headache" not further specified. Migraine was coded in 1973 cases, although almost one-third (12,467/41,808; 29.8%) of headache reports without a migraine code mention nausea or vomiting. The onset of symptoms was within 1 day of vaccination in over two-thirds of cases. The majority of reports were classified as not serious; about one-third involved emergency room or office visits. Of the 43,218 total headache reports, only a minority involved hospitalizations (2624; 6.1%) or permanent disability (1091; 2.5%), females accounted for 68.9% (29,771) and males for 29.5% (12,725), patients aged 6 to 59 years represented 67.3% (29,112), and over one-third of cases were reported after herpes zoster (8665; 20.1%) and influenza (6748; 15.6%) vaccinations.
Conclusion: In a national surveillance system, headache was a commonly reported post-vaccination adverse event; a small subset of reports was considered serious. The development of standardized vaccine-related case definitions could be useful for better evaluating headache as an adverse event during vaccine development, and may reduce vaccine hesitancy especially in headache-prone individuals.
Vaccines developed in response to the current and prior public health emergencies have been hugely successful. They are continuously monitored for safety by the U.S. Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA), who sponsor a national vaccine safety surveillance program called the Vaccine Adverse Events Reporting System (VAERS).[1,2] Significant injury and disability are important to evaluate. However, more common side effects of vaccinations, such as headache, are also important to evaluate because of the global burden associated with headache disorders.
Both randomized controlled trials as part of Phase 3 clinical studies[4,5] and previous post-licensure surveillance[6–8] have revealed headache is one of the most reported symptoms following vaccination. For example, headache was the first or second most commonly reported adverse event in studies of the quadrivalent live attenuated influenza vaccine (LAIV4), the trivalent live attenuated influenza vaccine (LAIV3), and the quadrivalent HPV vaccine, at frequencies of 18%, 16%, and 7.7%, respectively. Similarly, headache was the most commonly reported systemic adverse event following a herpes zoster vaccine (9.4%) and a quadrivalent inactivated influenza vaccine (31.8% for non-elderly and 16.1% for elderly) in clinical trials.
Although headache is a common symptom of vaccines, systematic investigations of post-licensure occurrence are lacking. Understanding headache reported as an adverse event following vaccination is fundamental as the perception of symptoms related to vaccines may result in non-compliance and negatively impact public health prevention programs.
We aimed to assess systematically the demographics, headache characterization and diagnoses, associated vaccines, and severity according to reporting in the VAERS database prior to the approval of coronavirus disease 2019 (COVID-19) vaccinations. We hypothesized post-vaccination headache would be commonly reported, although associated disability would be generally low.
Headache. 2023;63(2):275-282. © 2023 Blackwell Publishing