Background: The adverse events reported from the COVID-19 mRNA vaccines have varied from very mild, such as pain near the vaccination site, to more severe, with occasional anaphylaxis. Details of age-specific gender differences for the adverse effects are not well documented. Methods: Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20-65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules.
Keywords: COVID-19 vaccine; SARS-CoV-2; adverse events; gender differences; side-effects.