The severity of the coronavirus disease 2019 (COVID-19) in pregnancy and infancy is considered to be more severe than in children. As a result, it is necessary to evaluate the efficacy of vaccination or natural infection at inducing protective immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns.
A new Birth study examines the strength of this protection using antibody concentrations at birth and after six months in both mothers and children.
Study: Antibody Levels To SARS-Cov-2 Spike Protein in Mothers and Children from Delivery to Six Months Later. Image Credit: Lightspring / Shutterstock.com
Pregnancy induces many physiological changes that may predispose them to more severe COVID-19 than non-pregnant adults. Notably, there is considerable evidence that vertical transmission of COVID-19 to the fetus during pregnancy is very rare.
The presence of abundant angiotensin-converting enzyme 2 (ACE2) receptors throughout the placenta may elevate the risk of infection of this organ. The resulting placental injury, which allows it to leak inflammatory cytokines to the fetal circulation, could lead to detrimental fetal outcomes.
COVID-19 typically results in the production of neutralizing antibodies specifically targeting the SARS-CoV-2 spike antigen. These antibodies protect against severe disease and typically attach to epitopes on the spike’s receptor binding domain (RBD), which engages the ACE2 binding site. The presence of specific immunoglobulin M (IgM) and IgA in the blood and breastmilk, respectively, have been identified.
IgG antibodies cross the placenta into fetal circulation; however, IgM or IgA cannot be transferred to the fetus during pregnnacy. Thus, the presence of IgM and IgA is indicative of possible fetal infection.
In the current study, the authors used antibody titers in the serum and blood of pregnant women with SARS-CoV-2 infection, as well as in the umbilical cord blood of their babies at birth and six months, to assess the nature of maternal protection in infants. The study included over one hundred pregnant women with a median age of 34 years, over two-thirds of whom were infected within two weeks of childbirth or during labor.
Taken together, 71 newborns were included in the study, with a mean gestational age of 37 weeks. The majority of the newborns were born by vaginal delivery and breastfed, whereas less than 2% tested positive for COVID-19 during the course of the study.
Over 80% of the mothers were seropositive, with spike antibodies present at the time of childbirth. Almost 80% of cord blood samples were also positive; however, only two-thirds of breastmilk samples contained antibodies to the spike antigen.
Serum antibodies to the spike protein were correlated with cord blood antibodies; however, breastmilk samples failed to exhibit this association.
The earlier the infection during pregnancy, the more likely the mother was to have antibodies. While almost 95% of mothers had detectable IgG titers if infected more than two weeks before giving birth, two-thirds had IgM and IgA antibodies. A correlation was observed for the presence of antibodies in serum, cord blood, and breastmilk.
There were 15 babies without detectable IgG antibodies, almost all of whom were born to mothers infected within a month of delivery. Moreover, almost 90% of these infants were born to seronegative mothers, with most of the remaining infants born to mothers with IgG in their blood.
Similarly, about 67% of IgA-positive mothers had IgA in their breastmilk, whereas about 75% of IgA-negative mothers did not have detectable IgA titers in their serum or breastmilk. These findings indicate a close correlation between IgA levels in the blood and breastmilk.
IgG anti-spike were the most common antibodies identified in maternal serum and were thus higher than both IgA and IgM levels. Comparatively, in breastmilk, IgA levels were much higher as compared to both IgM and IgG levels.
In fetal blood, IgG was found in almost 80% of samples; however, other antibody classes were uncommon. On average, IgG levels in fetal blood were about 25% of the value observed in maternal blood.
Symptomatic women and their babies exhibited higher serum antibody levels by three- to five-fold.
Of the three babies who tested positive for COVID-19, only one tested positive at the time of delivery and was born to a seronegative mother who was ill at the time. The other two became positive 15 days from birth.
Cord blood IgG was found in only one baby whose mother was seropositive for all three Ig classes at the time. At six months, both mother and infant were seropositive.
In two cord blood samples, IgM levels were low, while IgA was low in three samples. All five samples were obtained from babies who were negative for COVID-19 but exhibited high IgG antibodies to the spike.
Of the paired samples, IgG levels remained high in most women at six months; however, about 33% of mothers exhibited a significant decline in their IgM levels to about 25% of those who were reported at birth. IgG levels declined throughout this period in 23 of the babies from over 400 to one.
Antibodies were also correlated with the blockade of spike-ACE2 receptor binding in maternal and cord blood serum, as well as in breastmilk. By six months, this antibody activity persisted at a higher level.
Anti-SARS-CoV-2 antibodies are generated by most pregnant women following infection and are detectable in both maternal serum and breastmilk. These antibody levels are higher in mothers who experienced symptomatic infection as compared to asymptomatic patients.
The placenta allows rapid and efficient transfer of IgG to the baby; however, IgG levels significantly declined over time. Conversely, antibody titers rose in mothers. Antibody titers were also correlated with neutralizing antibody titers, with the strength of correlation improving over time.
Taken together, neonatal passive immunity is conferred by the transfer of maternal antibodies, which is most efficient when the infection occurs earlier in pregnancy as compared to during the peripartum period. Disruption in antibody glycosylation, which is induced by SARS-CoV-2, may reduce the extent of such transfer, especially when COVID-19 occurs in the third trimester.
In the current study, most mothers were diagnosed with COVID-19 in the third trimester; however, this may not always indicate they were infected at that time. Notably, mothers with very low antibody levels were diagnosed near their delivery time, with most of the babies born to these mothers being seronegative.
The most important factor in neonatal antibody transfer is maternal serum IgG levels. The role of ethnicity and other medical conditions should also be examined.
It should also be noted that even if the time of maternal vaccination is not optimal for neonatal immunity, the COVID-19 vaccine will protect the mother from severe disease and adverse pregnancy outcomes.
The antibodies in breastmilk may prevent vertical transmission during breastfeeding as well. This effect is mediated by secretory IgA (sIgA) from the gut-associated lymphoid tissue (GALT), which binds to the Ig receptor to enter breastmilk by secretion. These high titers with accompanying neutralizing activity emphasize the importance of breastfeeding, even for mothers with COVID-19.
Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.”
- Martin-Vicente, M., Carrasco, I., Muñoz-Gomez, M. J., et al. (2022). Antibody Levels To SARS-Cov-2 Spike Protein in Mothers and Children from Delivery to Six Months Later. Birth. doi:10.1111/birt.12667.