Sex of Fetus Affects Immune Response to COVID-19 During Pregnancy

See “Sex Differences in Immune Responses to Viral Infection”

Yet little has been known about how pregnancy and COVID-19 affect one another. To find out, researchers at Massachusetts General Hospital and Harvard Medical School began biobanking blood and placenta samples in April 2020, according to STAT. In the new study, the research team analyzed placentas, maternal blood, and cord blood from 68 pregnant people, 38 of whom contracted COVID-19 during the third trimester of their pregnancies (all were unvaccinated, as this was before the vaccines were fully developed).

The team found that compared to placentas from pregnancies unaffected by COVID-19, in response to COVID-19 infection, male placentas that had been exposed to SARS-CoV-2 had higher expression of proinflammatory immune activation genes called interferon-stimulated genes (ISGs), and produced more cytokines, than female placentas. This shift may help protect male fetuses from infection, but inflammation in the uterus has also been linked to an increased risk of developing neurodevelopmental or metabolic disease later in life, according to a Massachusetts General Hospital press release. 

See “Maternal Obesity and Diabetes Linked to Autism in Children”

“What the downstream effects are going to be for the child we still don’t know,” Andrea Edlow, a maternal fetal medicine doctor at Mass General and assistant professor at Harvard Medical School, tells STAT. Edlow co-led the current study as well as another, also published in Science Translational Medicine, that looked at how pregnant people respond to vaccines. “But it’s definitely going to be important to follow up the development of these children on the basis of sex because we see these really profound changes in the placenta that suggest that the intrauterine environment is suddenly altered even in the setting of mild maternal disease.”

The sex of the fetus seemed to affect the immune response of the pregnant parent as well. SARS-CoV-2-infected patients produced fewer antibodies when carrying a male fetus than when carrying a female, meaning they also transferred fewer protective antibodies to male babies. In the press release, Edlow notes that this may leave males more susceptible to COVID-19 infection after birth, and that it could explain why pregnant people are more vulnerable to developing severe COVID-19.

Ruth Karron, a virologist and pediatric infectious diseases professor at the Johns Hopkins Bloomberg School of Public Health who was not involved in the study, tells STAT that even as scientists continue to tease apart the details of how pregnancy shapes responses to both infection and vaccination, the prevailing message must be that vaccination is important. “The data is of interest, but I think it doesn’t at this time have practical implications in terms of vaccine rollout other than what we already know—which is that 97% of pregnant people who have been hospitalized with Covid in this country are unvaccinated.”