Masked woman receives COVID-19 vaccine.

Why Do Men and Women React Differently to COVID-19 and the Vaccines?


The differences in severity and side effects in men’s and women’s experiences with COVID-19 and the vaccines may stem from various factors like genetics, sex hormones, and even sociocultural norms. Here are seven reasons why women and men differ in their experiences:

  • Men and women absorb drugs at varying rates.
  • Estrogen promotes and influences the immune response.
  • Testosterone suppresses the immune response.
  • Men have higher levels of enzymes that SARS-CoV-2 attaches to.
  • XX chromosomes come with more immunity genes.
  • Women are more open to sharing their symptoms compared to men.
  • Men take more lifestyle risks at the expense of their health.

Keep on reading to learn more about each finding.

1. Men and Women Absorb Treatments Differently

Studies show that women tend to absorb and metabolize medicine differently than men. Physical differences like body mass index (BMI), plasma volume, and body composition influence how drugs are distributed in the body. Since women have more fat stores and have smaller organs than men, they can get the same effects from lower doses of drugs.

2. Estrogen Activates the Immune Response More Effectively

Early studies have determined that women have enhanced antibody-producing capabilities thanks to female sex hormones like estrogen. Estrogen regulates the immune response by modulating B cells, influencing lymphoid tissue cells, and inducing T cell homing. This lets women’s immune systems mount an effective response to bacterial and viral infections.

What is a B cell? A type of white blood cell that works as a cleanup crew –– they don’t neutralize viruses themselves, but they connect to antigens on the surface of viruses, then transform into plasma cells that create antibodies that trap viruses.

What is a T cell? It is a type of white blood cell that works specifically to destroy foreign antigens and infected cells and relay chemical instructions (cytokines) to the rest of the immune system.

High immune reactivity also results in higher antibody levels in women post-vaccination. While this means women experience more adverse reactions than males following vaccination, it also means their bodies are developing high antibody responses that work to protect them more efficiently.

3. Testosterone Suppresses Immune Respons

Also known as androgens, male sex hormones like testosterone and dihydrotestosterone (DHT) have immunosuppressive qualities due to the way they modulate the breakdown of fat. Testosterone, for example, reduces proteins that regulate Module 52 genes –– these genes, when activated, result in suppressing an immune response. Studies demonstrate lesser antibody responses and lesser inflammatory cytokine expression in males given the influenza vaccine compared to women. In the same study, men with the highest testosterone levels had the worst response to the vaccine, whereas men with low testosterone levels had similar antibody responses as women.

4. Men Have High ACE2 Levels in Their Blood

ACE2 is a protein that lives on many cell surfaces in the lungs, heart, kidneys, gastrointestinal tract, blood vessels, and epithelial cells that create protective barriers. While it usually modulates proteins that damage blood vessels and tissues after an injury, SARS-CoV-2 binds to it and prevents it from doing its job. This contributes to respiratory injuries in COVID-19 patients.

Studies show that Angiotensin-converting enzyme 2 (ACE2) levels are higher in men than in women, especially in men with hypertension, diabetes, and cardiovascular disease –– leaving them more vulnerable to COVID-19 complications.

5. Extra X Chromosomes May Give Extra Immunity Advantages in Fighting COVID-19

A person’s genetic material can also influence how their body reacts to infections. Studies have shown that the X chromosome contains genes that relate to health. These help regulate immune functions thanks to genetic materials called microRNAs.

Females have two X chromosomes, one of which is inactivated in their embryo stage. But sometimes, some genes escape inactivation, and females end up having two copies of specific genes. And since the X chromosome contains 10% of all microRNAs, females will have two copies of microRNAs that play a role in an effective immune response –– something that is useful in the event of viral infections like COVID-19.

6. Women Are More Likely To Ask For Help

Symptoms of “Long COVID,” like exhaustion, body pain, insomnia, loss of taste and smell, hair loss, and blood clots, are more common among women. Besides biological differences, researchers note that a contributing factor is sociological –– women are simply more willing to report their symptoms and seek medical attention than men.

7. Men Engage in More Risky Lifestyle Habits

Another factor to why males are more vulnerable to COVID-19 is their gender behavior. Studies show that men engage in high-risk behaviors and lifestyle choices, such as smoking and drinking, which lead to pre-existing conditions that put them even more at risk of COVID-19 complications, such as heart disease.

While vaccine side effects sound severe or scary, this just means your body is making sure its immune defenses are fully working to protect you. Got more questions about COVID-19? Visit our information hub to get those questions answered, discover our Respiratory Clinic and Express Care location, or listen to our Inside Health podcast for in-depth expert knowledge about COVID-19.

Sources:
American Family Physician | Sex-Based Differences in Drug Activity
The Guardian | Not Accounting for Sex Differences in COVID Research Could be Deadly
The Journal of Immunology | The Effect of Estrone on Antibody-Production
National Center for Biotechnology Information | Sex Hormones Determine Immune Response
PubMed.gov | Sex-based Differences in Immune Function and Responses to Vaccination
Proceedings of the National Academy of Sciences of the United States of America | Systems Analysis of Sex Differences Reveals and Immunosyppressice Role for Testosterone in the Response to Influenza Vaccination
European Heart Journal | Circulating Plasma Concentrations of ACE2 in Men and Women with Heart Failure and Effects of RAAS Inhibitors
European Society of Cardiology | Men's Blood Contains Greater Concentrations of Enzyme That Helps COVID-19 Infect Cells
BioEssays | X-Chromosome-located MicroRNAs in Immunity: Might They Explain Male/Female Differences?
National Center for Biotechnology Information | Coronavirus: Why Men are More Vulnerable to COVID-19 Than Women?

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