Pregnant women carrying baby boys have fewer coronavirus antibodies than those carrying girls, a study found.
Pregnant women also transferred fewer antibodies to male fetuses than females, the findings showed.
The research offers a hint about how the male immune system responds to COVID-19.
It's one of the pandemic's most persistent mysteries: Why are men and boys more vulnerable to severe COVID-19 than women and girls?
A new study from Boston-based researchers suggests it may have to do with innate differences in their immune responses.
The study looked at 38 women who were infected with the coronavirus during pregnancy, half of whom were carrying baby boys. Most of the women had mild or moderate COVID-19. The researchers measured the levels of antibodies in the expectant mothers' blood, and the fetuses' antibody levels using placenta tissue and blood samples from the umbilical cords.
The results showed that the women pregnant with baby boys had fewer antibodies than those carrying girls. Additionally, pregnant women seemed to pass along fewer coronavirus antibodies to male fetuses than to females.
"There's obviously some crosstalk that's happening between the fetus and mother's immune system," Andrea Edlow, a maternal-fetal medicine specialist at Massachusetts General Hospital who co-led the study, told Insider.
The findings may hint at broader differences in how men and women respond to COVID-19. Male fetuses seemed to develop an inflammatory response to the virus that wasn't detected among female fetuses. Edlow said that inflammation may be interfering with a mother's ability to pass coronavirus antibodies to her unborn baby boy.
The male fetus 'lives dangerously on the edge of inflammation'
Researchers aren't sure if male fetuses respond to the coronavirus in the same way boys or adult men do, but there are some parallels.
The recent study found that in the placentas of women carrying male babies, there was an over-expression of interferon stimulated genes, which promote inflammation. But those same genes were under-expressed in the placentas of women with female fetuses.
"Those types of responses have been shown to be important in protecting the placenta and the fetus against infection when the mom has a viral infection," Edlow said. But she added that "it can also spill over into a harmful impact if it becomes too much."
Researchers have observed a similarly heightened immune response among men with COVID-19. A 2020 study found that infected men had higher levels of cytokines - proteins that can promote inflammation - than women with COVID-19. That could make them more vulnerable to severe disease.
Indeed, men represent the majority of COVID-19 deaths in the US (54%), despite making up the minority of recorded COVID-19 cases (48%). This pattern holds true across multiple age groups.
"There is a lot that has been written about how the male fetus - and maybe this extends later into male life - lives dangerously on the edge of inflammation, sort of skating by with just the right amount," Edlow said.
"I don't think that can fully explain the sex bias in COVID," she added, "but it does give us some hints into male immunity in general that starts in utero."
Researchers are looking at the effects of exposure to the virus in the womb
None of the fetuses examined in Edlow's study inherited a coronavirus infection, a finding that's consistent with her previous research. The babies were also delivered at a normal birth weights, and none of the pregnancies resulted in a miscarriage or stillbirth.
"What we don't know is: What are the longer-term impacts on the fetus who's developing in that inflammatory environment?" Edlow said.
So she's working with other researchers to see if exposure to the coronavirus in the womb has any effect on a child's development. Studies have shown that other diseases contracted by pregnant women could predispose their kids to neuro-developmental conditions like ADHD or autism, which are more common in boys.
"Whatever's happening in development seems to drive sex-biased risk for the child," Edlow said.
It's also unclear whether coronavirus antibodies inherited by the fetus translate into protection against COVID-19 outside the womb.
Health officials advise both pregnant women and vaccine-eligible kids to get COVID-19 vaccines regardless of whether they've been exposed to the virus before. The risk of dying from COVID-19 is nearly twice as high for pregnant women as it is for nonpregnant women of the same age.
Edlow's research has also shown that pregnant women develop a weaker-than-average immune response to the first dose of Pfizer's or Moderna's vaccine, rendering a second dose especially necessary.
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