Why do Women Experience Stronger Side Effects from the COVID-19 Vaccine?

Copyright free image from National Cancer Institute

With vaccine distribution rolling out all over the nation, scientists have been closely analyzing the new trends regarding the correlation between age, sex and dosage as well as the side effects of different COVID-19 vaccines. Based on data presented by the CDC, there have been more reports of adverse events experienced by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines [3]. The most common local and systemic reactions are pain in the area of the injection site, fatigue, headaches and myalgia [1]. The findings for both manufacturers were found to be similar to the clinical trials, demonstrating greater reactogenicity with the second dose of the Pfizer-BioNTech vaccine as compared to the first dose. Needless to say, there is a lot to be observed from these vaccines. The most notable observation from all of this data has been the significant difference in side effects faced by women compared to men; but, why exactly is this the case?

This data has not been surprising to physicians, given that women tend to experience more side effects and severe reactions to the annual flu vaccine [1]. There are other sociological factors and objections made that contribute to these trends, such as men being less likely to show emotion or speak up if they are experiencing any symptoms due to masculine stereotypes [1]. While these are all factors to consider, allergist, immunologist and infectious disease specialist Anne Liu at Stanford University School of Medicine explains that the biological differences between males and females plays a key role in why women experience stronger immune responses to vaccines than men [1]. In this scenario, women are experiencing stronger immune responses to the vaccines than men. This intensity in immune response has also provided reasoning as to why they are also the ones to experience the intense side effects. 

Furthermore, these displays of stronger immune response are supported by the findings that women and girls produce more of these infection-fighting antibodies whenever they receive vaccinations for influenza, yellow fever, hepatitis A, hepatitis B, and mMR compared to the average mean. While this may sound frightening, Rosemary Morgan, a scientist studying gender differences at Johns Hopkins Bloomberg School of Public Health, explains that this is a positive thing [1]. Since women have more robust immune responses, they are generally better in fighting off infections. Through a global COVID-19 meta-analysis, it was found that those who identified as male proved to be at a higher risk for death and intensive treatment unit (ITU) admission [5]. Based on the meta-analysis report, male patients were found to have almost three times the odds of necessitating ITU admission and higher odds of death due to COVID-19 [5]. While this seems like pleasant news for women, women are twice as likely to develop autoimmune diseases like lupus, rheumatoid arthritis and psoriasis, which is also another consequence and display of a strong immune response [6]. This background supports the finding of a majority of “long-haulers” — individuals who are COVID-19 survivors and experience symptoms that linger for months— be women [2]. Due to these conclusions, scientists hypothesize that the intense side effects experienced by women are not due to the virus itself, but rather the biological setup of immunity in women.

A particular facet of the differences in men and women’s immune systems is the role that hormones play. Higher levels of testosterone, as typically found in men, have been found to be linked to a weaker immune response [1]. This differs with estrogen and progesterone, which are linked to increasing the body’s defenses and leading to a stronger immune response. Researches have further studied sex as a biological factor through the potential therapeutic intervention of COVID-19 [4]. In order to test this, a group of men who were hospitalized with confirmed cases of COVID-19, ranging from moderate to severe, were given progesterone. The conclusion of this study was a display of improved clinical outcomes, which supports the idea of the role of hormones in the immune system. Another biological advantage to immunity lies in genetics. Dr. Panagis Galiatsatos, a physician in the Division of Pulmonary and Critical Care Medicine at Johns Hopkins Medicine, suggests that the genes related to immunity were found on the X chromosome [1]. Thus, by carrying two X chromosomes, women have an additional advantage.

Given the obvious biological differences between men and women, an important question to grapple within the coming months is whether both groups should receive the same dosage of vaccine. Though both groups receive the same dosage of the vaccine, an important question to consider is whether this amount is too much for women, leading them to suffer more from the side effects. All of these supported points are valid to conclude that it is not irregular for women to experience stronger side effects after receiving the COVID-19 vaccine; it is important to understand the biological basis of such trends to effectively explain their occurrence and reduce concern amongst vaccine hesitant populations.

Edited by:  Alexandra Dram
Illustrated by: Shelly Xu

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