Antibody levels were lower in unvaccinated, COVID-infected mothers at delivery and in their infants.
- Placentas from pregnancies with male fetuses show significantly higher levels of certain genes and proteins associated with increased immune activation during maternal SARS-CoV-2 infection. These genes and proteins may protect the placenta from viral infection, but may also promote inflammation.
- Women pregnant with male fetuses who contract SARS-CoV-2 make fewer antibodies against the virus and transfer less immunity to their infants compared to women carrying female fetuses.
- These findings demonstrate a strong influence of fetal sex on maternal and placental immune response and may provide insight into male vulnerability for severe COVID-19 illness in early life.
Andrea Edlow, MD, MSc
The sex of the fetus influenced both the mom’s ability to generate antibodies to COVID-19 and to transfer them to her baby.
Maternal-Fetal Medicine, Massachusetts General Hospital
BOSTON — In pregnant women who tested positive for SARS-CoV-2, the virus that causes COVID-19, male placentas demonstrated significantly higher levels of certain genes and proteins associated with increased immune activation compared with female placentas, according to a new study published in Science Translational Medicine. This increased immune activation may help protect male fetuses from becoming infected with SARS-CoV-2 in utero, but the resulting inflammation could pose risks to the fetus and child, notes Andrea Edlow, MD, MSc, senior author of the study and maternal-fetal medicine specialist at Massachusetts General Hospital (MGH).
Moreover, pregnant women with COVID-19 transferred significantly less immunity to the virus to male fetuses than to female fetuses, which could affect an infant’s risk for becoming infected with SARS-CoV-2. “The sex of the fetus influenced both the mom’s ability to generate antibodies to COVID-19 and to transfer them to her baby,” says Edlow. This is the first study to look at sex differences in the transfer of a mother’s antibodies from COVID infection to her fetus, and the first to examine sex differences in the placental response to maternal infection.
Epidemiological studies have shown that male adults, children and infants have a higher prevalence of COVID-19 infection and develop more severe disease than females. Male fetuses and infants are also more vulnerable to a host of pre- and perinatal exposures compared to female babies, so Edlow and her team sought to examine placentas, maternal blood and cord blood from pregnancies affected by maternal SARS-CoV-2 infection.
The study included 68 pregnant women, of whom 38 became infected with SARS-CoV-2 during their third trimester prior to the development of the COVID vaccine. The remaining 30 subjects were healthy pregnant women who tested negative for SARS-CoV-2 in pregnancy. In both groups, half the fetuses were male and half were female.
In a novel discovery, Edlow and her colleagues showed that, compared with female fetuses, the placentas of male fetuses carried by women with COVID-19 had much higher expression of interferon-stimulated genes (ISGs), which play a key role in shielding fetuses from viral invaders in utero. However, the increased expression of ISGs and downstream production of immune cells called cytokines can also result in an inflammatory intrauterine environment, which has been associated with an increased risk for neurodevelopmental or metabolic disease later in life. “While our study didn’t assess those risks specifically, it raises the importance of following these children and looking at male and female fetuses differently,” says Edlow.
In a second significant finding, Edlow’s team showed that mothers with COVID-19 who have male fetuses make lower levels of antibodies against the virus than mothers with female fetuses; they also transfer fewer antibodies to a male fetus. That suggests that males may be more vulnerable to becoming infected with SARS-CoV-2 in infancy and demonstrates that the sex of the fetus can influence the maternal immune response to the virus, notes Edlow.
Next, Edlow and her co-investigators plan to examine the character of antibodies induced by the COVID-19 vaccine and how those are affected by the timing of the vaccine during pregnancy and of course, fetal sex. “We want to know what happens to the placenta when moms are vaccinated against COVID-19 in each of the three trimesters and how fetal sex affects that response,” says Edlow.
Major funding for this study was provided by the National Institutes of Health and the March of Dimes.
Edlow is an assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School (HMS) and principal investigator at the Vincent Center for Reproductive Biology at MGH. Evan A. Bordt, PhD, is a research fellow in Pediatrics at MGH. Lydia Shook, MD, is a maternal-fetal medicine fellow in Obstetrics and Gynecology at MGH. Caroline Atyeo is a virologist at the Ragon Institute of MGH, MIT and Harvard. Krista M. Pullen is a doctoral student at MIT. Kathryn J. Gray, MD, PhD, is associate obstetrician at Brigham and Women’s Hospital and an assistant professor of Obstetrics, Gynecology and Reproductive Biology at HMS. Douglas Lauffenburger, PhD, is professor of Biological Engineering, Chemical Engineering, and Biology at MIT.
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of “America’s Best Hospitals.”
Related News and Articles
- Press Release
- Jan | 13 | 2022
First study to detect Delta variant of SARS-CoV-2 in maternal bloodstream and placenta in cases of stillbirth and pregnancy complications
Findings help elucidate earlier research suggesting that the Delta variant is a threat in pregnancy.
- Press Release
- Oct | 19 | 2021
Pregnant and lactating women should adhere closely to recommended COVID-19 vaccine schedules to attain full antibody protection
Certain antibody functions were delayed in pregnant and lactating women following the first dose. The second vaccine dose was critical to achieving full immunity in pregnant and lactating women.
- Press Release
- Mar | 25 | 2021
Pregnant and lactating women show robust immune response to COVID vaccines, pass antibodies to newborns
In the largest study of its kind to date, researchers have found the new mRNA COVID-19 vaccines to be highly effective in producing antibodies against the SARS-CoV-2 virus in pregnant and lactating women.
- Press Release
- Mar | 25 | 2021
Las mujeres embarazadas y lactantes muestran una sólida respuesta inmunitaria a las vacunas contra el COVID y transmiten los anticuerpos a los recién nacidos
En el mayor estudio de este tipo realizado hasta la fecha, los investigadores han descubierto que las nuevas vacunas de ARNm contra el COVID-19 son muy eficaces para producir anticuerpos contra el virus del SARS-CoV-2 en mujeres embarazadas y lactantes.
- Press Release
- Dec | 22 | 2020
Pregnant women with COVID-19 don’t pass virus to newborns, but also may pass fewer-than-expected antibodies to newborns
A group led by investigators at Massachusetts General Hospital (MGH) provides new insights that could help improve care for these women and their newborns and emphasizes the need for pregnant women to be considered in vaccine rollout plans.