Post-Vaccination Headache Reporting

In This Article

Abstract and Introduction

Abstract

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.

Introduction

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.^[3]

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),^[8] the trivalent live attenuated influenza vaccine (LAIV3),^[7] and the quadrivalent HPV vaccine,^[6] 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%)^[9] and a quadrivalent inactivated influenza vaccine (31.8% for non-elderly and 16.1% for elderly)^[10] 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.

Table 1. The seven most common vaccine types for reports of headache in the Vaccine Adverse Events Reporting System database.
Vaccine type	Headache (n = 43,218)	All symptoms^a (n = 536,120)
Zoster vaccine (Varzos)	8665 (20.1%)	75,810 (14.1%)
Influenza virus vaccine, trivalent (injected) (FLU3 [seasonal])	6748 (15.6%)	83,892 (15.7%)
Tetanus and diphtheria toxoids and acellular pertussis vaccine (Boostrix/Adacel) (Tdap)	3727 (8.6%)	35,179 (6.6%)
Hepatitis B vaccine (Hep)	2995 (6.9%)	36,131 (6.7%)
Human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (HPV4)	2932 (6.8%)	36,213 (6.8%)
Pneumococcal vaccine, polyvalent (PPV)	2860 (6.6%)	53,120 (9.9%)
Meningococcal vaccine (Menactra) (MNQ)	2474 (5.7%)	21,684 (4.0%)

^aPercentages for reports of all symptoms included for reference.

Table 2. Post-vaccination headache categories of severity for reports of headache in the Vaccine Adverse Events Reporting System database.
Serious^a	Event category^b	Events reported	Percent of total headache reports (n = 43,218)
No		30,837	71.4%
	Emergency room/office visit	13,135	30.4%
Yes		12,381	28.6%
	Hospitalized	2624	6.1%
	Emergency room/office visit	2269	5.3%
	Permanent disability^c	1091	2.5%
	Life-threatening^d	698	1.6%
	Existing hospitalization prolonged	198	0.5%
	Death	89	0.2%

Note: Definitions of terms in the notes below are according to the Vaccine Adverse Events Reporting System.
^aSerious: "Any adverse event occurring at any dose that results in any of the following outcomes: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition."
^bEvent category (outcome of the event as categorized into one or more of the following options): death, life threatening, permanent disability, congenital anomaly or birth defect, hospitalized, existing hospitalization prolonged, emergency room/office visit, emergency room, office visit, and none of the above. Note that the following three categories were added June 30, 2017: emergency room (only), office visit (only), congenital anomaly or birth defect. When the data are grouped by Event category, the number of categories mentioned in the Events reported column is likely to exceed the number of unique events, because a single event may fall into more than category.
^cDisability: A substantial disruption of a person's ability to conduct normal life functions.
^dLife-threatening: Any adverse experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse event as it occurred, that is, it does not include an adverse event that, had it occurred in a more severe form, might have caused death.