7 Reasons Why 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. Let’s dive deeper into the differences.

1. Men and Women Metabolize Drugs 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 throughout the body. Since women have more fat stores and smaller organs compared to men, they can often get the same effects from lower doses of drugs.

2. Estrogen Helps Activate Immune Response

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 May Inhibit Immune Response

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 Higher Plasma ACE2 Levels

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 Women More Immunity Advantages With 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 Report Symptoms

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 High-Risk Behaviors

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. Listen to Dr. Syed Raza (VP of Medical Operations at St. Luke’s Health–The Woodlands Hospital), Dr. Charles Sims (Infectious Disease Specialist at Baylor St. Luke’s Medical Group), and Dr. Jefy Mathew (Chief of Pulmonary and Critical Care and Medical Director of the Intensive Care Units at St. Luke’s Health–The Woodlands Hospital) talk about the COVID-19 vaccines in this episode of the Smart Health podcast: