COVID-19 Infection During Pregnancy Can Cause Immune Changes in Mothers and Infants

Investigators from the Cleveland Clinic sought to understand the clinical and immunological implications of COVID-19 on maternal-to-fetal health.

“We know that pregnancy increases maternal risk for COVID-19, but relatively little is known about the long-term consequences of in utero exposure for infants,” said Jae Jung, PhD, director of the Cleveland Clinic Global Center for Pathogen and Human Health Research.

The study, published in Cell Reports Medicine, included 93 mothers with COVID-19 and 45 of their infants who were exposed to the virus. The investigators compared maternal blood specimens collected close to the original date of COVID-19 infection and throughout pregnancy and delivery. They studied immune profiles for over 1400 cytokines and other inflammatory proteins from the subjects’ peripheral and cord blood samples.

At delivery, the women had dysregulated levels of many cytokines associated with pregnancy complications, such as MMP7, MDK, ESM1, BGN and CD209. The infants expressed induction of T cell-associated cytokines IL33, NFATC3, and CCL21. While most births were healthy, there was high incidents of certain complications like fetal growth restriction and preeclampsia.

Jung reported, “Our findings show that COVID-19 infection during pregnancy leads to distinct immune alterations in mothers and babies, highlighting how important it will be for long-term follow-up after pregnancy to catch and hopefully prevent any unforeseen long-term health conditions related to prenatal infection.”

The investigators found different immune signatures between pregnant women with asymptomatic and severe COVID-19 infection. The mothers with severe disease had significantly more inflammation and elevated levels of the protein interferon lambda 1 (IFNL1) and its binding receptor, IFNLR1.

“This increase in interferon lambda signaling may help explain why we see relatively little direct transmission of COVID-19 between mother and baby during the period right before or after birth—what we call vertical transmission,” said Suan-Sin (Jolin) Foo, PhD, the study’s co-first author.

There was no robust data suggesting vertical transmission, but the investigators found COVID-19 infection altered the mothers’ immunity at delivery, and gestational COVID-19 exposure alters the immunity of the newborns.

“More research will be necessary to determine if increased expression of IFNL1 and IFNLR1 does in fact block vertical transmission,” Foo said.