Questionnaire-based study of COVID-19 vaccination induced headache: evidence of clusters of adverse events.

Background: The adverse events (AEs) after a Coronavirus disease 2019 (Covid-19) Pfizer-Biotech mRNA vaccination present a medical and epidemiological issue of increasing interest. Headache is the most frequent neurological adverse effect and generally the third most common adverse event after a Covid-19 vaccination, but only a few studies focus on the link between headache and other AEs after vaccination. This study aims to investigate the correlation between headaches and Covid-19 vaccination, as well as the possible links between headaches and other AEs after Covid-19 vaccination, thereby helping the management of AEs and avoiding further occurrences.

Methods: This study is based on a published questionnaire survey of 1,402 healthcare workers. Our study focused on the 5 questions including 12 AEs and headaches extracted from the questionnaire post the first and second Covid-19 vaccination. The severity of the 12 AEs and headaches could be classified by the participants on a five-step scale: "Not at all", "Little", "Average", "Quite", and "Very" (abbreviated as "N", "L", "A", "Q", "V"). We used the Bowker test to study the comparison of headache severity, indicated on a 5-point Likert scale between the first and second vaccinations. We applied an ordinal logistic regression to the 5 categories with headache severity serving as the dependent variable and the ratings of the other 12 AEs serving as the independent variable to further explore to what extent the severity of the 12 AEs is associated with the severity of headaches. Receiver Operating Characteristic (ROC) analysis was conducted to evaluate the predictive value of the ratings of the 12 AEs to headache severity.

Results: We found that participants rated their headaches as more severe after the second vaccination, and participants who reported experiencing fatigue, flu-like symptoms, pain at the injection site, known tension-type headache, fever, dizziness/balance problems and known migraine are associated with headache symptoms.

Conclusions: There are clusters of headache-associated AEs post Covid-19 vaccination. The association of various AEs with headaches may be due to similar causative mechanisms.