Experts cautiously optimistic that virus doesn’t target fetus during first trimester.

Authors: MEREDITH WADMAN August 7. 2022 SCIENCE

When a pregnant woman gets sick, her doctors have two patients: the woman and her fetus. While obstetricians work to understand COVID-19’s impact on mothers-to-be (see main story, p. 606), they are also carefully tracking the virus’ impact on the fetus, acutely aware that other viruses, including Zika, cytomegalovirus (CMV), and rubella, can cause serious birth defects. Researchers are cautiously optimistic the same will not prove true with the new coronavirus.

A case study published last month demonstrated conclusively that fetuses can be infected late in pregnancy. But such infections appear to be “extremely rare,” says lead author Daniele De Luca, a critical care neonatologist at Paris Saclay University Hospitals AP-HP. Stanley Plotkin, a physician-scientist who invented the widely used rubella vaccine, notes: “This is not rubella.” The 1964 epidemic of that disease led to the births of tens of thousands of damaged babies in the United States.

It’s still too soon to be certain that fetuses won’t be damaged if they are infected during the sensitive first trimester, when tissues and organs take shape. But Carolyn Coyne, a virologist who studies placental infections at the University of Pittsburgh, is optimistic. “If [the virus] was a devastating pathogen causing fetal malformations early in pregnancy, we would have very clear cases from China,” which had the earliest surge of COVID-19 cases. Senior Chinese obstetricians contacted by Science said they had seen no cases of congenital anomalies but warned that numbers were too small to draw firm conclusions.

Plotkin notes rubella and CMV are commonly blood-borne, allowing those viruses to reach the placenta during the first trimester, before it is a fully formed barrier to viral invasion. “Although SARS-CoV-2 virus does occasionally get into the blood, it is not basically a [blood-borne] infection,” he says. “That’s important.”

In one study of nearly 700 pregnant women admitted to three New York hospitals for delivery, 71 babies born to infected moms were uninfected themselves. Another study published this month in eLife suggests the virus is unlikely to easily invade placental cells. Scientists led by Roberto Romero at the National Institute of Child Health and Human Development and Wayne State University found placental cells rarely simultaneously express a pair of molecules that the virus relies on to invade cells: ACE2, a membrane-bound receptor, and TMPRSS-2, an enzyme that activates the virus after it has bound ACE2. By contrast, they found that receptors for Zika and CMV are abundant on placental cells.

Still, a mother’s SARS-CoV-2 infection could affect her fetus’ growth. Researchers in the New York study also examined placentas from a subset of women and found clots in blood vessels on the fetal side of the placenta in nearly half—14 of 29—of COVID-19–infected mothers. Only 11% of placentas—12 out of 106—from uninfected moms had similar clots. Another study, by researchers at Northwestern University, found significantly more blood vessel injury and clots on the maternal side of the placenta in 15 of 16 infected women than in controls.

Blood clots could limit the oxygen and nutrients delivered to the fetus. These studies suggest the need to closely monitor fetal growth during the second half of a COVID-19–affected pregnancy, says Malavika Prabhu, a maternal and fetal medicine specialist at Weill Cornell Medicine and first author on the New York study.

Meanwhile, she and others await a wave of babies conceived early in the pandemic and due in the fall. “If you have COVID-19 at 8 weeks during embryonic development, what is the outcome for that baby? That’s data that needs time to gestate,” says Yalda Afshar, a high-risk obstetrician at Ronald Reagan University of California, Los Angeles, Medical Center.