In Utero SARS-CoV-2 Transmission Unlikely, but Neonates May Be Unprotected

Jake Remaly

January 05, 2021

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No maternal viremia, placental infection, or vertical transmission of SARS-CoV-2 occurred during a biorepository study that included 64 women with SARS-CoV-2 infection, researchers reported in JAMA Network Open.

But SARS-CoV-2 antibodies transferred relatively inefficiently across the placenta in the third trimester, which suggests that neonates whose mothers had COVID-19 during pregnancy still may be vulnerable to the virus, the investigators said. Antibodies may transfer more efficiently with second-trimester infections, data from another study indicate.

"These findings suggest that, although low rates of maternal viremia and patterns of placental SARS-CoV-2 receptor distribution may underlie the rarity of vertical transmission, reduced transplacental transfer of anti–SARS-CoV-2 antibodies may leave neonates at risk for infection," wrote study author Andrea G. Edlow, MD, MSc, and colleagues. Edlow is an assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School and a maternal-fetal medicine specialist at Massachusetts General Hospital, both in Boston.

In another study published in Cell, the research team found that, unlike with third trimester infections, SARS-CoV-2 antibodies transferred efficiently after infection in the second trimester. "Understanding how de novo antibody transfer varies by trimester may point to critical windows in pregnancy that may be most desirable for induction of antibodies through vaccination to optimize protection for both the mother and her infant," they wrote.

It is unclear whether antibodies that are elicited by recently authorized vaccines will transfer differently than those elicited by natural infection.

Reassurance, Questions, and Concerns

"Although it is not known whether the inefficient transplacental transfer of antibodies ... will also extend to antibodies elicited by future SARS-CoV-2 vaccines, it underscores the susceptibility of infants," said Denise J. Jamieson, MD, MPH, of Emory University, Atlanta, and Sonja A. Rasmussen, MD, MS, of the University of Florida, Gainesville, in an editorial accompanying the JAMA Network Open study.

And while the lack of vertical disease transmission in this study is reassuring, more research is needed, according to the director of a federal institute that helped fund the research.

"This study provides some reassurance that SARS-CoV-2 infections during the third trimester are unlikely to pass through the placenta to the fetus, but more research needs to be done to confirm this finding," said Diana W. Bianchi, MD, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, in a news release.

The study authors theorize that the low incidence of maternal viremia and nonoverlapping expression of SARS-CoV-2 receptors ACE2 and TMPRSS2 in the placenta may protect against placental infection and vertical transmission.

Testing at 3 Centers

To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids and the transplacental passage of anti–SARS-CoV-2 antibodies, Edlow and collaborators enrolled 127 pregnant women at three tertiary care centers in Boston between April 2 and June 13, 2020. Follow-up occurred through July 10. Researchers tested neonates born to women with SARS-CoV-2 infection by nasopharyngeal swab at age 24 hours.

Of 64 women with SARS-CoV-2 infection, 36% were asymptomatic, 34% had mild disease, 11% had moderate disease, 16% had severe disease, and 3% had critical disease. Viral load analyses did not detect viremia in maternal or cord blood, and there was no evidence of vertical transmission.

Transfer of anti–SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza antibodies The average cord-to-maternal antibody ratio was 0.72 for anti–receptor binding domain IgG and 0.74 for antinucleocapsid, whereas the ratio for anti-influenza antibodies was 1.44. The expected cord-to-maternal antibody ratio is approximately 1.5 for pathogens such as pertussis, influenza, and measles, the authors noted.

Among participants who tested positive for SARS-CoV-2, 35-week intrauterine fetal demise occurred in an asymptomatic woman, and 22-week neonatal demise secondary to extreme prematurity in the setting of abruption and preterm labor occurred in a symptomatic patient.

Maternal disease severity was significantly associated with detectable respiratory viral load. In addition, disease severity was positively correlated with serum concentration of C-reactive protein and ALT, and negatively correlated with white blood cell count.

In the Cell study that further examined antibody transfer, the investigators focused on maternal and cord blood plasma samples from 22 mother-cord dyads with SARS-CoV-2 infection during pregnancy and 34 uninfected mother-neonate dyads, as well as a second trimester cohort of 29 mother-neonate dyads and a third trimester validation cohort of 28 mother-neonate dyads.

Protecting Infants

The results support "previous studies that have found that, while intrauterine transmission is possible, it is not common," Jamieson and Rasmussen noted. "Most viral infections can be transmitted transplacentally; however, why some viruses are transmitted relatively easily across the placenta (e.g., HIV, Zika, herpes simplex virus), while others, such as influenza, are transmitted rarely is not well understood."

Data indicate that infants are at higher risk of severe COVID-19, compared with older children. Nonetheless, research suggests that strict hygiene measures can protect infants born to mothers with SARS-CoV-2 infection, they added.

The research was supported by the National Institutes of Health; the Cystic Fibrosis Foundation; a gift from Mark, Lisa, and Enid Schwartz; and by the Massachusetts General Hospital department of pathology Vickery-Colvin Award and other nonprofit groups. Edlow, Jamieson, and Rasmussen had no conflict of interest disclosures.

The coauthors of both studies disclosed ties to pharmaceutical companies, grants from foundations and government agencies, a patent for a SARS-CoV-2 vaccine, and author royalties from publishers.

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