A recent study published on the preprint server medRxiv* in October 2020 shows that newborns may be protected from acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by antibodies in the mother’s blood that travels through the placenta.
Newborns typically have weak immune responses and rely on maternal antibodies transferred through the placenta to protect against many infections. It is essential to understand the degree of transplacental transfer following severe COVID-19 since this determines the extent of protection it affords. This will also shape the right strategy for vaccination of expectant mothers once COVID-19 vaccines are available.
Using Matched Samples to Understand Transplacental Transfer of Antibodies
As of now, only case reports and some small case series have been reported in this area. The current study looks at serum and cord blood samples from the mother and baby of paired subjects in a Philadelphia hospital, where the women presented for delivery between April 9, 2020, and August 8, 2020. The samples were not especially drawn for the purpose of the study but were destined for disposal.
All expectant mothers were routinely screened for COVID-19 or SARS-CoV-2 infection by polymerase chain reaction (PCR) testing of nasopharyngeal specimens. This was carried out when the woman came to hospital for delivery, as well as being offered during pregnancy following suspected exposure to an infected individual or one with symptoms of COVID-19.
The researchers measured maternal and neonatal IgG and IgM antibodies against the SARS-CoV-2 spike receptor-binding domain (RBD) antigen. They found that of ~1,700 women delivered in this period, matched paired samples were available for ~1,470 dyads.
Most Newborns of Seropositive Mothers are Seropositive
Using a cut-off at 0.48 arbitrary units to denote seropositivity, they determined that among these mothers, ~6% were seropositive. Of the infants born to these mothers, 87% were seropositive – which comes to 72 infants. None of the babies born to seronegative women were seropositive.
No Babies Born to PCR-Positive Women are PCR-Positive
The results of the PCR tests showed that 54% of the seropositive women had tested PCR-positive at some point in pregnancy. Most of them had no history of COVID-19 symptoms, and all the babies born to them were PCR-negative. This was the case even if the mother was positive and contagious at the time of delivery, though the infant was tested at 24-48 hours after delivery.
Maternal Serum Antibody Level Correlates with Cord Blood Antibodies
The level of SARS-CoV-2 IgG in cord blood correlated with that in the mother’s serum in all the 72 seropositive infants. None of the samples tested positive for IgM, however. Among the 11 seronegative infants born to seropositive mothers, making up 13% of this group altogether, the mothers had only IgM antibodies above the cut-off. In the 6 remaining infants, the IgG levels in the mothers were much lower (measured by the geometric mean level) than in the mothers with seropositive infants.
The researchers then looked at the relationship between the severity of the maternal infection and the IgG levels in maternal and cord blood. They found a trend towards higher IgG and IgM levels in mothers with a moderate and critical disease, with higher cord blood IgG levels in the babies born to these mothers. The trend fell short of significance, however.
High Transplacental Transfer Ratio
The ratio of IgG in infant to maternal blood, called the transplacental antibody transfer ratio, was found to be comparable in all seropositive infants irrespective of the severity of the maternal disease. The cord blood IgG was found to double that in the maternal blood.
Using the date of viral testing in symptomatic women as a surrogate for the onset of infection, they found that the transfer ratio went up with the duration from PCR testing and delivery in women with symptomatic COVID-19, with a positive PCR before delivery at term.
The high transfer ratios that could go above 2 in the current study, where most women had term deliveries, indicates the “efficient transplacental transfer of IgG antibodies from SARS-CoV-2 seropositive pregnant women.”
Again, the association of higher maternal antibody levels with higher cord antibody levels is important, as is that of increasing duration from onset of maternal infection to delivery and higher cord blood antibody levels. These agree with earlier studies.
However, it remains true that the transfer of antibodies can be affected by the occurrence of maternal infections in pregnancy, the type of IgG elicited, placental disease, and gestational age at birth, along with chronic maternal immunodeficiency.
They also found that the demographic characteristics as well as the health of the woman during pregnancy were not related to the seropositivity of cord blood. Preterm and term deliveries had the same transfer ratio up to 31 weeks preterm.
Vertical Spread of SARS-CoV-2 Unlikely
These findings show that even though SARS-CoV-2 transmission has been reported to the placenta and the newborn, it is an uncommon event. Two reports from China indicate the presence of IgM antibodies against the virus in the newborns, but the occurrence of false-positive results cannot be ruled out. The current study did not reveal the presence of IgM in cord blood in any sample, irrespective of critical or severe maternal illness.
This supports the hypothesis that maternal-fetal transmission is rare with SARS-CoV-2. A more pressing issue is whether vertical transmission could occur after birth, either from the mothers or other family members who are infected and contagious.
Implications and Future Directions
The large number of participants who had all come for delivery over the study period allowed the researchers to avoid selecting women who were found to be infectious during pregnancy or delivery. However, the results could not be correlated with the outcome since the specimens were retrospectively examined.
The researchers note that among neonates born to women who had a positive test following symptom onset, which was used to denote the time of onset of infection, all cord blood samples tested positive for antibodies to SARS-CoV-2 if at least 17 days had elapsed since the date of PCR testing.
Further research will determine if these antibodies are protective against newborn infection, and the level of protection conferred. These studies will show if transplacental antibodies generated by vaccination act like those produced as a result of infection.
The authors summarize: “Our findings demonstrate the potential for maternally-derived antibodies to provide neonatal protection from SARS-CoV-2 infection, and will help inform both neonatal management guidance as well as the design of vaccine trials during pregnancy.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.