NEWS

If You Contract COVID During Pregnancy, the Sex of Your Baby Matters—Here's Why

Pregnant person wearing a face mask.

Guido Mieth / Getty Images

Key Takeaways

  • Males are more likely to have severe outcomes from a SARS-CoV-2 infection.
  • A new study looking at pregnant people with COVID-19 found that proteins and genes associated with immune responses were higher in male fetuses than female fetuses.
  • The researchers also discovered that maternal antibody transfer was lower when pregnant people were carrying male fetuses compared to female fetuses.

During the COVID-19 pandemic, data has shown that severe disease is more likely to occur in males than in females. But why the disease manifests itself differently based on sex is still a mystery.

To look into these differences between the sexes, researchers from Massachusetts General Hospital decided to study the placentas, maternal blood, and cord blood of pregnancies affected by a COVID-19 case.

They found that the placentas of pregnant people with male fetuses had higher levels of interferon-stimulated genes (ISGs) than female fetuses. These genes and proteins are associated with increased immune activation. The results were published in a new study published in Science Translational Medicine last month

While these genes help protect fetuses from viral infections, they may also contribute to dangerous inflammation.

Viral Infections Can Vary Between Sexes

COVID-19 infection rates appear to be similar for both sexes, but adult males tend to experience a more severe course of the disease compared to females.

“Males develop greater inflammatory immune responses, including cytokine production, within the first week of diagnosis with severe disease, and we have shown that this contributes significantly to male-biased severe outcomes, including death,” Sabra Klein, PhD, a microbiologist at the Johns Hopkins Bloomberg School of Public Health, tells Verywell.

Cytokines help regulate inflammatory responses in the body, but when they overproduce this can cause an excessive inflammatory reaction called “cytokine storm” that contributes to severe COVID-19 complications.

However, sex differences in the severity of viral infections are not limited to COVID-19. 

Infections caused by the hepatitis B and C viruses tend to be more prevalent and intense for males. Meanwhile, infections caused by the herpes simplex virus type 2 (HSV2) and human immunodeficiency virus (HIV) cause more severe diseases in females. This means that sex affects a person's immunity to viruses as well as their outcomes once infected.

“Sex differences are reported for both innate and adaptive immune responses to viruses,” Klein says. “For adaptive immunity, females often have greater T cell responses, including responses of T cells that kill virally infected cells than males and greater antibody responses. We and others have shown this in mice and humans.”

What’s the Difference Between Innate and Adaptive Immune Response?

Innate immunity is the first-line, non-specific response to any breach of our bodies. We are born with it. Adaptive immunity is a learned immune response.

Age-related changes, as well as sex differences in growth factors and repair mechanisms that fix damaged tissue after infection, may also play a role in these differences between the sexes, Klein adds. 

“There are a number of studies illustrating that male fetuses are more susceptible to adverse outcomes from perturbations, whether genetic, environmental, or infection-related than female fetuses,” Klein says. “Male babies are more susceptible to death from infectious and noninfectious insults after birth.”

What This Means For You

Pregnant people are at an increased risk for severe COVID-19 disease. If you're pregnant, it's important that you get fully vaccinated against COVID-19. You can find an available appointment here.

How a Fetus's Sex Influences Immune Responses

“Early on in the pandemic, it became clear that males fared worse against SARS-CoV-2 infection compared to females, and we wondered whether this male immune vulnerability might even start in utero,” Evan Bordt, PhD, first author of the study and instructor of pediatrics at Harvard Medical School and the Lurie Center for Autism at Massachusetts General Hospital, tells Verywell.

They discovered that the sex of the fetus may influence maternal and placental immune responses.

Placental Immune Responses

The study involved 68 participants—38 of whom got infected with the virus during pregnancy. The researchers included people who were pregnant with both males and females to study how a maternal COVID-19 infection would affect them differently.

“Pregnant women are often left out of drug trials and other research,” Bordt says. “This was the case with early COVID-19 vaccine trials, leading to many pregnant women feeling confused about whether or not they should receive the vaccine. We hope that we can protect and empower pregnant women by including them in research, rather than by excluding them.”

The placentas of male fetuses carried by pregnant people with COVID-19 were found to have higher levels of antiviral proteins called interferons, compared to the placentas of female fetuses. Although this inflammatory response can protect the fetus against the viral infection, too much of it may harm their development.

“The immune system is very resilient," Bordt says. "While we don’t at this point know the long-term effects of this increased interferon response during gestation, it will be important to follow the development of these children, paying particular attention to sex.”

Reduced Antibody Transfer to Male Fetuses

The researchers found that the sex of the fetus can influence the maternal immune response to the virus.

“We know that maternal infection with other viruses such as Zika virus impacts both the mother and the fetus,” Bordt adds. “Maternal immune activation, such as a viral infection, can have lasting effects upon the baby, and we wanted to study what effects pregnancy would have on both maternal and fetal immune responses.”

The study shows that people who were pregnant with a male fetus generated fewer antibodies against the virus than those who carried a female fetus. Because they have fewer antibodies themselves, they also transfer fewer of these potentially protective antibodies to the male baby.

This finding demonstrates how the sex of the fetus can affect the maternal immune response, which then affects the fetal immune response as well.

“Babies are protected against infections early in their lives by antibodies that are transferred from mother to fetus via placental receptors,” Bordt says. “Different receptors transfer different antibodies more or less effectively."

People who are infected with SARS-CoV-2 and are pregnant with male fetuses may have a less efficient antibody-receptor combination than those who carry female fetuses. This may explain why the maternal antibody transfer to a male fetus is worse, he adds.

For Klein, the findings might be suggestive of evolved differences in fetal responses to infection.

“If antibodies more readily traverse placentas of female fetuses, then the female fetus and resulting placenta may not have evolved the need for heightened interferon responses because they are better protected by maternal immunity," she says.

Overall, the study provides significant data on sex-specific placental innate and adaptive immune responses to maternal COVID-19 infection.

"While I think that we are a bit far from understanding how this impacts the origins of sex differences in immunity, these data do show that maternal infection—even with a virus that does not infect the placenta—can impact maternal transfer of immunity and fetal responses to infection," Klein adds.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

Was this page helpful?
4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Jacobsen H, Klein S. Sex Differences in Immunity to Viral InfectionsFrontiers in Immunology. Published online August 31, 2021. doi:10.3389/fimmu.2021.720952

  2. EA Bordt, Shook LL, Atyeo C, et al. Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses. Science Translational Medicine. 19 Oct 2021;13(617). doi:10.1126/scitranslmed.abi7428

  3. Centers for Disease Control and Prevention. COVID-19 Vaccines While Pregnant or Breastfeeding. Updated October 19, 2021.

  4. EA Bordt, Shook LL, Atyeo C, et al. Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses. Science Translational Medicine. 19 Oct 2021;13(617). doi:10.1126/scitranslmed.abi7428.