Are women at higher risk of Covid-19 vaccine-related adverse events?

Data to date shows a preponderance of Covid-19 vaccine-related adverse events (AEs) among women compared to men. This finding may be due to the generally more robust immunological response to infections and vaccines among women, increased reporting of AEs by women, genetic factors, microbiome differences as well as other factors.1-3

A CDC study involving mRNA vaccines (Pfizer and Moderna) during the 1st month of vaccination roll out in the US, found that nearly 80% of adverse events were reported by women.  The great majority (>90%) of these AEs were not serious and included symptoms such as headache, dizziness and fatigue.1

A JAMA study involving individuals receiving one of the mRNA vaccines found that 94% (Pfizer) and 100% (Moderna) of anaphylaxis events occurred among women. Of note, the median age was ~40 years  with the majority of anaphylaxis events were reported after the first dose. 2

Higher incidence of AEs following Covid-19 vaccination is not surprising and may be explained biologically. Women typically have a more robust immune response to infections and vaccination, both at the level of innate and adaptive immunity with higher antibody responses.  

These findings may be in part due to hormones such as estrogen which is known to enhance differentiation of dendritic cells and proinflammatory cytokine production. Other proposed mechanisms include differences in microbiome between sexes and sex-based genetic influences on humoral immune profile with the X chromosome expressing 10 times more genes than the Y chromosome, including genes that influence immunity.3

Bonus Pearl: Did you know that anaphylactic reaction to the mRNA Covid-19 vaccines is extremely rare, occurring in only 2-5 cases/ million!2

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  1. Gee J, Marquez P, Su J, et al. First month of Covid-19 vaccine safety monitoring—United States, December 14, 2020—January 13, 2021. MMWR 2021;70:283-88.
  2. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA Covid-19 vaccines in the US—December 14, 2020-January 18, 2021. JAMA 20201;325:1101-1102.
  3. Fischinger S, Boudreau CM, Butler AL, et al. Sex differences in vaccine-induced humoral immunity. Semin Immunopath 2019;41:239-49.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Are women at higher risk of Covid-19 vaccine-related adverse events?

My patient with abdominal pain needs a CT scan with IV iodinated contrast, but reports a “shellfish” allergy? Is she at high risk of allergic reaction to IV contrast?

Patients with shellfish allergy appear not to have a significantly higher rate of allergic reactions to iodinated contrast media compared to patients with history of atopy, such as asthma or other food allergies 1,2.  When true shellfish allergy occurs, it is caused by an immunological reaction to the protein, not iodine, content of the food ingested.  “Iodine allergy” cannot exist because iodine is found throughout our bodies and is essential to life. 

The typical IV contrast-related adverse reaction is caused by non-IgE-mediated mast cell and basophil degranulation due to the high osmolality of these agents. Because the resultant “anaphylactoid” reaction is not associated with prior immune system memory, its risk is not increased by previous exposure to IV contrast.  Premedication with corticosteroids and diphenhydramine may be effective in reducing the risk of such reactions, but is not routinely recommended in patients with isolated history of shellfish allergy2.



  1. Schabelman E, Witting M. The relationship of radioconstrast, iodine, and seafood allergies: a medical myth exposed. J Emerg Med 2010;39: 701-707.
  2. Westermann-Clark E, Pepper AN, Talreja N, Lockey RF. Debunking myths about “allergy” to radioconstrast media in an academic institution. Postgrad Med 2015;127:295-300.
My patient with abdominal pain needs a CT scan with IV iodinated contrast, but reports a “shellfish” allergy? Is she at high risk of allergic reaction to IV contrast?