Epidemiological Aspects of Headache After Different Types of COVID-19 Vaccines

An Online Survey

Rehab Magdy MD; Diana Khedr MD; Osama Yacoub MD; Abeer Attia MD; Mona A. Abdelrahman MD; Doaa Mekkawy MD


Headache. 2022;62(8):1046-1052. 

In This Article

Abstract and Introduction


Background: Coronavirus disease 2019 (COVID-19) vaccine–related side effects are a key concern with the emergence of various types of vaccines in the market. We aimed to assess the frequency and characteristics of headache following different types of COVID-19 vaccines.

Methods: Fully vaccinated people were recruited by a convenience sample through an online survey from September 1 to December 1, 2021. Detailed analysis of headache following vaccination was investigated. Participants with a history of pre-existing headaches were telephone interviewed by a neurologist to ascertain the type of headache.

Results: A total of 1372 participants participated (mean age 32.9 ± 11.1). The highest frequency of headache was reported with the adenoviral vector type (302/563, 53.6%), followed by mRNA vaccines (129/269, 48%) and then the inactivated type (188/540, 34.8%). Recipients of the adenoviral vector type had a significantly longer latency between vaccination and the headache onset (median 8 h [5:12]) than recipients of the inactivated type (median 4 h [2:8], p < 0.001). Headache intensity was significantly higher with the adenoviral vector type (median 6 [5:8]) than with the inactivated type (median 5 [4:7], p < 0.001). Adenoviral vector vaccines would increase the likelihood of headache by 2.38 times more than inactivated vaccines (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.83–3.04, p < 0.001). Female sex and thyroid disease were significantly associated with headache related to COVID-19 vaccines (OR 1.52, 95% CI 1.16–1.99; OR 3.97, 95% CI 1.55–10.2, respectively).

Conclusion: Recipients of the COVID-19 vaccine should be counseled that they may experience headaches, especially after the adenoviral vector type. However, the intensity of such headache is mild to moderate and can resolve within a few days. Based on the current study design and the potential recall bias, these results may not be generalizable and should be preliminary.


Coronavirus disease 2019 (COVID-19) has become a global pandemic. COVID-19 vaccines have progressed worldwide as the most promising approach to prevent infections.[1]

Regarding COVID-19 vaccines, different types have been proposed with different mechanisms of action, such as: inactivated viral vaccine (VACSERA Sinovac [Vac Sinovac] and Sinopharm BBIBP vaccines), the newly announced mRNA vaccines (Pfizer and Moderna), and adenoviral vector–based vaccines (AstraZeneca, Johnson & Johnson, and Sputnik V vaccines).[1–3] The latter type presents a safe, modified version of the virus—known as "the vector," the spike protein found on the surface of the coronavirus carrying the genetic code for the antigen.[4]

Although the safety of COVID-19 vaccines has been broadly accepted, several randomized controlled trials have reported adverse effects in the hours/days following vaccination. They are usually mild or moderate and resolve within a few days after vaccination.[5,6]

According to the available data, the most common neurological symptom is headache in more than 50% of vaccinated individuals after the first and the second doses.[7] The International Classification of Headache Disorders, 3rd edition (ICHD-3) does not list any diagnostic criteria for headache related to COVID-19 vaccine.[8] However, when studying the characteristics of such headaches, the type of vaccine and its mechanism of action must be considered.

We hypothesized that headaches are the most common among the recipients of the adenoviral vector type rather than other vaccines based on the fact that the adenoviral vector vaccines can provoke more immunogenic responses than the other types.[9,10]

We aimed in this study to compare different types of available COVID-19 vaccines regarding frequency and in detail the clinical characteristics of headache related to COVID-19 vaccine, and to study the predictors of such headache.