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In general, women’s immune systems respond more powerfully to illnesses. Raquel Arocena Torres/Getty Images
  • Experts say women’s immune systems have a stronger initial response to most illnesses.
  • However, they note the strong response can cause some long-term health issues, including the development of autoimmune diseases.
  • They say the differences in immune systems can be partly attributed to hormones and chromosomes.
  • They say this information could help in developing more specialized treatments for men and women.

A man and a woman both test positive for COVID-19.

The man has more severe symptoms while the woman has milder symptoms.

Yet, as time passes, the man recovers quickly while the woman experiences lingering symptoms of Long COVID.

Why? Females have a stronger immune response than males and experts say this isn’t just confined to COVID-19.

“In general, almost all infections are more severe in males compared to females and there are just a few exceptions with that and one is with whooping cough or pertussis,” Dr. Dean Blumberg, the chief of Pediatric Infectious Diseases at the University of California Davis, told Healthline.

However, according to Blumberg, the stronger immune response in women can be a positive and a negative thing.

“It’s a good thing in that it helps fight off infection, so… it should lead to quicker recovery, and less severe illness,” he explained. “On the other hand, if it’s too strong, then the immune system can [experience] collateral damage, resulting in damage of tissue or organs and autoimmune diseases. So, that’s the balance that needs to be like Goldilocks. It needs to be just right in terms of fighting infection but not causing damage to the host.”

Gender is a recognized variable that can influence the response of the immune system.

A 2016 study that examined the differences in the immune response of the sexes noted that the function of the immune system can vary significantly between males and females, resulting in notable variation in the prevalence of certain diseases as well as mortality rates.

The study authors wrote that “80 percent of autoimmune disease occurs in females. Women with acute HIV infection have 40 percent less viral RNA in their blood than men. Men show an almost twofold higher risk of death from malignant cancer than women and antibody responses to seasonal influenza vaccines are consistently at least twice as strong in women than men.”

“Generally, adult females mount stronger innate and adaptive immune responses than males,” the authors continued. “This results in faster clearance of pathogens and greater vaccine efficacy in females than in males but also contributes to their increased susceptibility to inflammatory and autoimmune diseases.”

The researchers also found that differences in immune response between the sexes changes over the lifespan, with both age and reproductive status playing a role.

Dr. Caitlin McAuley, DO is a family medicine specialist and physician who sees patients through the Keck Medicine of USC COVID Recovery Clinic.

She says there are a number of potential reasons why women mount a stronger immune response than men.

“The theory is the effects of hormones, specifically estrogen, there may also be genetic differences in the immune system based on differences between the X and Y chromosomes,” McAuley told Healthline. “Further, it has been proposed that this is due to an evolutionary benefit as females are important for reproduction of the species.”

“There are hormone receptors present in different aspects of our immune system involved in signaling and balance. We also know that hormones affect gene expression. The thymus, an important immune system organ, will actually change in size based on estrogen levels,” she added.

“Estrogen affects not only the development of immune cells but also the chemicals they release called cytokines,” she said.

Almost every human has 23 pairs of chromosomes, including one pair of sex chromosomes. Known as the X and Y chromosomes, sex chromosomes determine the biological sex of a person.

Females have two X chromosomes and males have one X and one Y chromosome.

According to the Centers for Disease Control and Prevention, X chromosomes have a higher density of genes related to the immune system.

Given that women have two X chromosomes compared to men only having one, women typically mount a stronger immune response.

“This differential regulation of immune responses in men and women is contributed by sex chromosome genes and sex hormones, including estrogen, progesterone, and androgens,” the CDC states.

The immune response refers to how the body defends itself against viruses, bacteria and other foreign substances that may appear harmful.

Innate immunity is the form of immunity a person is born with that helps them protect the body. It is considered the first line of defense for the immune system and includes the skin, the coughing reflex, and mucus which can assist in trapping bacteria.

Dr. Hector Bonilla, a clinical associate professor of medicine in the division of infectious diseases at Stanford University in California, says there is a difference in the innate immune system between males and females.

“Immunological differences between males and females are exemplified by the fact that androgen response elements and estrogen response elements reside in the promoters of several genes of the innate immune system,” he told Healthline.

It is this difference that could play a role in the different experiences of the sexes in COVID-19 infection.

“As the immune system undergoes a complex process of maturation from birth to adult age, differences in the immune and inflammatory response could have a significant impact in determining the spectrum of severity of COVID-19,” Bonilla said.

The different immune responses of the sexes represent a growing body of research with COVID-19 highlighting yet more differences in female and male defense systems.

Blumberg says gaining a better understanding of the immune response of the sexes could help pave the way for more targeted and effective treatments for both men and women.

“It might help personalize therapy so that we can optimize outcomes. There may be different therapies or different doses of medications for men and women to result in better outcomes,” he said.

“In some cases, you wouldn’t want to rev up the immune system too much,” Blumberg noted. “For example, in women that might result in too many side effects and on the other hand, for men, they may need more of a boost to get them over the hump to treat infections and cure infections.”

“So that would be the sort of nuances that we’d be dealing with. I think right now our treatments are relatively crude and not as personalized as they can be,” he said.