Pregnant women who have contracted Covid are at higher risk for severe disease than people who aren’t pregnant, and a new study is shedding light on how the body’s immune response may differ depending on whether you’re carrying a boy or a girl. 

According to a recent study released in Science Translational Medicine, researchers discovered that if you’re carrying a male baby, your immune system produces fewer antibodies to fight infection than if you’re carrying a female baby.

The immune system during pregnancy

Pregnant women are very vulnerable to disease. In general, many of the cells that make up the immune system have estrogen receptors, and when exposed to additional estrogen during pregnancy, depending on the cell type, immune cells will increase or decrease in number, change their function or produce more or less of certain proteins—and these changes could make for a weaker or more powerful immune system. During pregnancy, a woman’s immune system is suppressed in order to carry the pregnancy to term and not reject the baby, which is not recognized as belonging to the mother.

The placenta also plays a critical role in immune function, producing antiviral responses when exposed and transferring antibodies from the mother.

Male babies’ placentas elicit a heightened immune response

In the early days of the pandemic, it was evident that pregnant women were getting hit harder by Covid than many other population groups, getting sick more often and more severely. 

So in April 2020, researchers at Massachusetts General Hospital and Harvard Medical School began investigating by biobanking and analyzing maternal blood, cord and placenta samples from 68 pregnant women, 38 of whom contracted Covid during the third trimester of their pregnancies (as this was before vaccines were available, none were vaccinated). The researchers found that, compared to placentas from pregnancies unaffected by Covid, in response to Covid infection, male babies’ placentas switched on more pro-inflammatory immune activation genes than placentas supporting female babies.

Researchers are unsure why this happens, but they suspect this increased immune activation might help male babies fend off Covid. 

They also found that not only did boy babies in utero elicit a different immune response, but male babies seemed to affect the immune response of their mother as well. Covid-infected mothers produced fewer antibodies in response to the virus if their baby was a boy. And they also transferred far fewer of these protective antibodies to their growing baby boy. 

“What’s striking here is that the mothers who are carrying male babies have much lower levels of antibodies to the coronavirus,” Akiko Iwasaki, a virologist and immunologist at Yale University who was not involved in the study, tells STAT. “We knew that maternal infection can significantly impact the fetus, but this means that there is cross-talk between the fetus and the mother. What’s interesting about that is it means that the sex of the baby can dictate how the mother responds to a viral infection.”

More research is needed

One limitation to the research is that the pregnant women were primarily in their third trimester, so it is not known if Covid infection in the first and second trimesters alters placental immune function. And even though the research did not find time from infection to delivery to be a substantial contributor to the reduced antibody transfers in boy babies, that timing cannot be ruled out. 

It’s also important to note that this study focused on a relatively small number of pregnant women. Larger trials are warranted to confirm the results. 

As with everything associated with Covid, theories outnumber high-quality studies, but one thing is clear: As more solutions are found, pregnant women need to be studied more often to ensure representation of their unique vulnerability.

To that end, the Pregnancy Coronavirus Outcomes Registry at the University of California San Francisco is collecting data from more than 1,100 US pregnant women to answer urgent questions such as: the impact on mother and fetus of drugs being given to fight Covid, how infection influences a mother's immune status, and whether and how anti-clotting drugs ought to be used in pregnant women with Covid.

Sources

Bordt EA, et al. Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses. Science translational medicine 13.617 (2021): eabi7428. doi:10.1126/scitranslmed.abi7428

Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nature Reviews Immunology 8.9 (2008): 737-744. doi:10.1038/nri2394

Taylor BD, et al. The impact of female fetal sex on preeclampsia and the maternal immune milieu. Pregnancy hypertension vol. 12 (2018): 53-57. doi:10.1016/j.preghy.2018.02.009