Maternal COVID Antibodies Cross Placenta, Detected in Newborns

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Antibodies against SARS-CoV-2 cross the placenta during pregnancy and are detectable in most newborns born to mothers who had COVID-19 during pregnancy, according to findings from a study presented January 28 at the virtual Society for Maternal-Fetal Medicine (SMFM) 2021 Annual Pregnancy Meeting.

Dr Naima Joseph

"I think the most striking finding is that we noticed a high degree of neutralizing response to natural infection even among asymptomatic infection, but of course a higher degree was seen in those with symptomatic infection," Naima Joseph, MD, MPH, of the Emory University School of Medicine, Atlanta, Georgia, told Medscape Medical News.

"Our data demonstrate maternal capacity to mount an appropriate and robust immune response," and maternal protective immunity lasted at least 28 days after infection, Joseph said. "Also, we noted higher neonatal cord blood titers in moms with higher titers, which suggests a relationship, but we need to better understand how transplacental transfer occurs as well as establish neonatal correlates of protection in order to see if and how maternal immunity may also benefit neonates."

The researchers analyzed the amount of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in maternal and cord blood samples prospectively collected at delivery from women who tested positive for COVID-19 at any time while pregnant. They used enzyme-linked immunosorbent assay to assess for antibodies for the receptor binding domain of the SARS-CoV-2 spike protein.

The 32 pairs of mothers and infants in the study were predominantly non-Hispanic Black (72%) and Hispanic (25%), and 84% used Medicaid as their payer. Most of the mothers (72%) had at least one comorbidity, most commonly obesity, hypertension, and asthma or pulmonary disease. Just over half the women (53%) were symptomatic while they were infected, and 88% were ill with COVID-19 during the third trimester. The average time from infection to delivery was 28 days.

All the mothers had IgG antibodies, 94% had IgM antibodies, and 94% had neutralizing antibodies against SARS-CoV-2. Among the cord blood samples, 91% had IgG antibodies, 9% had IgM antibodies, and 25% had neutralizing antibodies.

"It's reassuring that so far, the physiological response is exactly what we expected it to be," Judette Louis, MD, MPH, an associate professor of ob/gyn and the ob/gyn department chair at the University of South Florida, Tampa, Florida, told Medscape Medical News. "It's what we would expect, but it's always helpful to have more data to support that. Otherwise, you're extrapolating from what you know from other conditions," said Louis, who moderated the oral abstracts session.

Symptomatic infection was associated with significantly higher IgG titers than asymptomatic infection (P = .03), but no correlation was seen for IgM or neutralizing antibodies. In addition, although mothers who delivered more than 28 days after their infection had higher IgG titers (P = .05), no differences existed in IgM or neutralizing response.

Infants' cord blood titers were significantly lower than their corresponding maternal samples, independently of symptoms or latency from infection to delivery (P < .001), Joseph reported.

"Transplacental efficiency in other pathogens has been shown to be correlated with neonatal immunity when the ratio of cord to maternal blood is greater than 1," Joseph said in her presentation. Their data showed "suboptimal efficiency" at a ratio of 0.81.

The study's small sample size and lack of a control group were weaknesses, but a major strength was having a population at disproportionately higher risk for infection and severe morbidity than the general population.

Implications for Maternal COVID-19 Vaccination

Although the data are not yet available, Joseph said they have expanded their protocol to include vaccinated pregnant women.

"The key to developing an effective vaccine [for pregnant people] is in really characterizing adaptive immunity in pregnancy," Joseph told SMFM attendees. "I think that these findings inform further vaccine development in demonstrating that maternal immunity is robust."

The World Health Organization recently recommended withholding COVID-19 vaccines from pregnant people, but the SMFM and American College of Obstetricians and Gynecologists subsequently issued a joint statement reaffirming that the COVID-19 vaccines authorized by the FDA "should not be withheld from pregnant individuals who choose to receive the vaccine."

"One of the questions people ask is whether in pregnancy you're going to mount a good response to the vaccine the way you would outside of pregnancy," Louis said. "If we can demonstrate that you do, that may provide the information that some mothers need to make their decisions." Data such as those from Joseph's study can also inform recommendations on timing of maternal vaccination.

"For instance, Dr Joseph demonstrated that 28 days out from the infection, you had more antibodies, so there may be a scenario where we say this vaccine may be more beneficial in the middle of the pregnancy for the purpose of forming those antibodies," Louis said.

Consensus Emerging From Maternal Antibodies Data

The findings from Joseph's study mirror those reported in a study published online January 29 JAMA Pediatrics. That study, led by Dustin D. Flannery, DO, MSCE, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, also examined maternal and neonatal levels of IgG and IgM antibodies against the receptor binding domain of the SARS-CoV-2 spike protein. They also found a positive correlation between cord blood and maternal IgG concentrations (P < .001), but notably, the ratio of cord to maternal blood titers was greater than 1, unlike in Joseph's study.

For their study, Flannery and colleagues obtained maternal and cord blood sera at the time of delivery from 1471 pairs of mothers and infants, independently of COVID status during pregnancy. The average maternal age was 32 years, and just over a quarter of the population (26%) were Black, non-Hispanic women. About half (51%) were White, 12% were Hispanic, and 7% were Asian.

Six percent of the women had either IgG or IgM antibodies at delivery, and 87% of infants born to those mothers had measurable IgG in their cord blood. No infants had IgM antibodies. As with the study presented at SMFM, the mothers' infections included asymptomatic, mild, moderate, and severe cases, and the degree of severity of cases had no apparent effect on infant antibody concentrations. Most of the women who tested positive for COVID-19 (60%) were asymptomatic.

Among the 11 mothers who had antibodies but whose infants' cord blood did not, five had only IgM antibodies, and six had significantly lower IgG concentrations than those seen in the other mothers.

In a commentary about the JAMA Pediatrics study, Flor Munoz, MD, of the Baylor College of Medicine, Houston, Texas, suggested that the findings are grounds for optimism about a maternal vaccination strategy to protect infants from COVID-19.

"However, the timing of maternal vaccination to protect the infant, as opposed to the mother alone, would necessitate an adequate interval from vaccination to delivery (of at least 4 weeks), while vaccination early in gestation and even late in the third trimester could still be protective for the mother," Munoz writes.

Given the interval between two-dose vaccination regimens and the fact that transplacental transfer begins at about the 17th week of gestation, "maternal vaccination starting in the early second trimester of gestation might be optimal to achieve the highest levels of antibodies in the newborn," Munoz writes. But questions remain, such as how effective the neonatal antibodies would be in protecting against COVID-19 and how long they last after birth.

No external funding was used in Joseph's study. Joseph and Louis have disclosed no relevant financial relationships. The JAMA Pediatrics study was funded by the Children's Hospital of Philadelphia. One coauthor received consultancy fees from Sanofi Pasteur, Lumen, Novavax, and Merck unrelated to the study. Munoz served on the data and safety monitoring boards of Moderna, Pfizer, Virometix, and Meissa Vaccines and has received grants from Novavax Research and Gilead Research.

Society for Maternal-Fetal Medicine (SMFM) 2021 Annual Pregnancy Meeting: Abstract LB01. Presented January 28, 2021.

JAMA Pediatrics. Published online January 29, 2021.

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