Q&A: Pregnant women with COVID-19 pass few antibodies to infants

Although the risk for vertical transmission of COVID-19 appears rare, a lower-than-expected rate of transplacental transfer of antibodies suggests children born to infected mothers may be at risk for infection, according to a study published in JAMA Network Open.

Researchers conducted a prospective cohort study in pregnant women who presented at three tertiary care centers in Boston. They recruited pregnant women who tested positive for COVID-19 with reverse transcription-polymerase chain reaction (RT-PCR) tests from April 2, 2020, through June 13, 2020, and enrolled patients who tested negative as a convenience sample.

Researchers evaluated SARS-CoV-2 viral load in pregnant women’s plasma or respiratory fluids, umbilical cord plasma, anti-SARS-CoV-2 antibodies in women’s plasma and in umbilical cord plasma, and SARS-CoV-2 in the placenta.

A total of 127 pregnant woman — 64 who tested positive for SARS-CoV-2 and 63 who tested negative — were included in the study.

Among those who tested positive, 36% were asymptomatic, 34% had mild disease, 11% had moderate disease, 16% had severe disease and 3% had critical disease.

Of the 107 women who had viral load analyzed, researchers did not identify detectible viremia in their blood or umbilical cord blood, and they did not find evidence of vertical transmission. Of the 77 infants tested who had SARS-CoV-2 antibodies quantified in umbilical cord blood, just one had detectable immunoglobuilin M to nucleocapsid.

Researchers did not detect SARS-CoV-2 RNA in any of the 88 placentas tested.

During an analysis of antibodies in 37 women with SARS-CoV-2, researchers found that anti-receptor binding domain immunoglobin G was detected in 65% and anti-nucleocapsid was detected in 70%.

In an editorial comment published alongside the study, Denise J. Jamieson, MD, MPH, professor and chair of the department of gynecology and obstetrics at the Emory University School of Medicine in Atlanta, and Sonja A. Rasmussen, MD, MS, professor in the department of pediatrics and epidemiology at the University of Florida College of Medicine, wrote that while more research is needed to determine whether the observed inefficient transplacental transfer of SARS-CoV-2 antibodies from mothers to infants will apply to antibodies elicited by COVID-19 vaccines, it highlights the susceptibility of infants to infection.

“These findings underscore the importance of ensuring that pregnant women are included in SARS-CoV-2 vaccine clinical trials so they have the opportunity to receive SARS-CoV-2 vaccines once they are found to be safe and effective,” they wrote. “It also highlights the importance of protecting pregnant women and their newborns from exposure to SARS-CoV-2 infection.”

Healio Primary Care spoke with study author Andrea G. Edlow, MD, MSc, a maternal-fetal medicine specialist at Massachusetts General Hospital and an assistant professor of obstetrics, gynecology and reproductive biology at Harvard Medical School, to learn more about the findings and what they suggest about COVID-19 vaccination in pregnant women.

Q: What do these findings suggest about COVID-19 vaccination efforts in pregnant women?

I think the implications for the COVID-19 vaccine in pregnant women are nuanced. In the JAMA Network Open paper, we found reduced placental antibody transfer of anti-COVID antibodies from mom to fetus in third trimester infection. This was an unexpected finding. In our recent paper in Cell, we looked at the mechanism underlying this and found it was at least in part related to different patterns of glycosylation — sugar or carbohydrate attachments to the antibodies — on COVID-19-specific antibodies. The COVID-19 antibodies had sugar groups attached to them that may have reduced the efficiency of placental transfer to the fetus, and caused them to be “stuck” in maternal circulation rather than attaching to placental receptors and crossing over to the umbilical cord blood. These findings have implications for both rational vaccine design specific to pregnant women — vaccines that induce antibodies with sugar attachments that transfer most efficiently will give the best neonatal protection — and for the timing of vaccination in pregnancy, as second trimester infection resulted in more efficient transfer of antibodies than 3rd trimester. We also don’t know if antibodies from vaccines will have the same sugar attachment profile as antibodies from natural infection with COVID-19, so that is something important to study going forward. In addition, having more antibodies around in the maternal blood is generally associated with higher transfer to the neonate, so to the extent that vaccination may boost the amount of antibody in the mother’s system compared to native infection — an important area of study — vaccination might be helpful to facilitate increased transfer to the neonate.

Q: How does transplacental transfer of antibodies to the fetus observed in women with COVID-19 compare with influenza?

A: Transfer of anti-COVID-19 antibodies is lower than transfer of anti-flu antibodies or transfer of anti-pertussis antibodies.

Q: What additional research is needed to determine the impact of maternal COVID-19 infection on infant immunity?

A: Evaluation of transfer efficiency with maternal infection in the first, compared to second, compared to third trimester. We also are evaluating antibody transfer to neonates in breastmilk and will study the antibodies generated by the vaccine in both pregnancy and lactation.

Q: What could be preventing transmission of COVID-19 from pregnant mothers to their infants?

A: Low prevalence of maternal viremia — presence of detectable virus in the bloodstream — and a protective pattern of the SARS-CoV-2 entry receptor (ACE2) and protease (TMPRSS2) in the placenta, both of which were demonstrated in the JAMA Network Open paper.

Q: Based on these findings, should hospitals that separate infants from mothers with COVID-19 continue to do so?

A: No, mothers and infants should not be separated. Our work does not contain findings that are relevant to mother-infant separation per se, but it has been demonstrated in other studies that with good hand hygiene and careful masking/precautions taken, neonates can safely room in with mothers and mothers can breastfeed with a mask on and after careful hand/breast hygiene. Massachusetts General Hospital and most other hospitals across the country do not separate mothers and neonates even when the mother is positive for COVID-19.

References:

Atyeo C, et al. Cell. 2020;doi:10.1016/j.cell.2020.12.027.

Edlow AG, et al. JAMA Netw Open. 2020;doi:10.1001/jamanetworkopen.2020.30455.

Jamieson DJ, et al. JAMA Netw Open. 2020;doi:10.1001/jamanetworkopen.2020.30564.