Mother-to-Child Transmission of SARS-CoV-2 May Be Underestimated

Tara Haelle

October 11, 2022

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ANAHEIM, Calif. — The rate of mother-to-child transmission of SARS-CoV-2 infection is likely higher than the current estimate of 2%-8%, suggests a recent study using cord blood serology to determine incidence. The study was presented at the annual meeting of the American Academy of Pediatrics.

"Cord blood screening is a potential tool to identify SARS-CoV-2 infected and/or exposed neonates who should then be followed for long-term consequences of mother-to-child transmission," Amy Yeh, MD, an assistant professor of clinical pediatrics at the University of Southern California, Los Angeles, told attendees at the meeting.

Yeh and her colleagues collected cord blood from more than 500 mothers at LAC+USC Medical Center from October 2021 to April 2022 and tested them for IgG antibodies against three SARS-CoV-2 antigens: nucleoprotein (N), receptor-binding domain (RBD), and spike protein (S1). Results with an IgG mean fluorescence intensity (MFI) above 700 were considered positive for IgG antibodies. A positive result for N as well as RBD or S1 indicated a natural infection while a positive result for only RBD or S1 indicated a vaccine response or past infection.

The researchers also tested a subset of the IgG positive samples for IgM and IgA antibodies against N, S1, and RBD, with an IgM MFI greater than 24 and an IgA MFI greater than 102 used as the thresholds for positive results.

Among 384 cord blood samples analyzed, 85.4% were positive for IgG against RBD, indicating that the mother had SARS-CoV-2 immunity from either a past infection or vaccination. Of these anti-RBD positive samples, 60.7% were anti-N IgG negative, suggesting that N had waned since vaccination or the past infection.

Since the other 39.3% that were anti-N IgG positive suggest a past maternal infection, the researchers assessed these 129 samples for IgM and IgA antibodies against RBD. They found that 16 of them had high levels of anti-RBD IgA and/or IgM antibodies, pointing to a rate of mother-to-child-transmission of up to 12.4%.

Sallie Permar, MD, PhD, a professor and the chair of pediatrics at Weill Cornell Medicine in New York, who was not involved in the research, said most studies of placental transmission have focused on virologic testing, such as PCR. "Serologic tests for congenital infections are inherently challenged by the transfer of maternal IgG across the placenta and therefore must rely on non-IgG isotype response detection, which have inherently been more susceptible to false-positive results than IgG-based tests," Permar said.

Also, "it is unclear if virologic testing was performed in the infants, which, if positive in the same infants for which cord blood IgM/IgA responses were identified, could further validate positive serologic findings," added Permar, who is also pediatrician-in-chief at New York-Presbyterian Komansky Children's Hospital.

Given these limitations, Permar reiterated that diagnostics for congenital SARS-CoV-2 continue to evolve, even if congenital SARS-CoV-2 infection currently appears rare. Permar said she agreed with Yeh that following those who do develop this infection is important.

"There have been initial reports of neurodevelopmental and other outcomes from long-term follow-up cohorts of infants exposed to SARS-CoV-2 infection in utero with variable results and it should continue to be pursued using cohorts both enrolled early in the pandemic and those enrolled more recently after population-level immunity to SARS-CoV-2 was achieved," said Permar.

Permar serves as a consultant to Moderna, Pfizer, Merck, Dynavax, and Hoopika on their CMV vaccine programs and has led sponsored research programs with Moderna and Merck. Information on study funding and on disclosures for Yeh was unavailable.

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