The severity of coronavirus disease 2019 (COVID-19) during pregnancy and childhood is considered to be more severe than in children. As a result, it is necessary to evaluate the efficacy of vaccination or natural infection to induce protective immunity against coronavirus 2 (SARS-CoV-2) of severe acute respiratory syndrome 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 in SARS-Cov-2 ear protein in mothers and children from birth to six months later. Image credit: Lightspring / Shutterstock.com
Introduction
Pregnancy induces many physiological changes that can predispose them to more severe COVID-19 than nonpregnant adults. In particular, there is considerable evidence that vertical transmission of COVID-19 to the fetus during pregnancy is very rare.
The presence of abundant angiotensin 2 converting enzyme (ACE2) receptors throughout the placenta may increase the risk of infection of this organ. The resulting placental injury, which allows it to filter out inflammatory cytokines in the fetal circulation, could lead to detrimental fetal outcomes.
COVID-19 typically results in the production of neutralizing antibodies specifically targeted to the SARS-CoV-2 spike antigen. These antibodies protect against serious disease and typically bind to the epitopes of the spike receptor binding domain (RBD), which attaches to the ACE2 binding site. The presence of specific immunoglobulin M (IgM) and IgA in blood and breast milk, respectively, has been identified.
IgG antibodies cross the placenta into the fetal circulation; however, IgM or IgA cannot be transferred to the fetus during pregnancy. Thus, the presence of IgM and IgA is indicative of a possible fetal infection.
In the current study, the authors used serum and blood antibody titers from pregnant women with SARS-CoV-2 infection, as well as the umbilical cord blood of their babies at birth and at six months, to assess the nature of maternal protection. in babies. The study included more than one hundred pregnant women with a mean age of 34 years, more than two-thirds of whom were infected in the two weeks after or during childbirth.
Altogether, 71 newborns were included in the study, with a mean gestational age of 37 weeks. Most babies were born vaginally and were breastfed, while less than 2% tested positive for COVID-19 during the course of the study.
Study results
More than 80% of mothers were HIV-positive, with peak antibodies present at the time of delivery. Nearly 80% of cord blood samples were also positive; however, only two-thirds of breast milk samples contained antibodies against spike antigen.
Serum spike protein antibodies were correlated with cord blood antibodies; however, breast milk samples could not show this association.
The earlier the infection during pregnancy, the more likely the mother was to have antibodies. Although nearly 95% of mothers had detectable IgG titers if infected more than two weeks before delivery, two-thirds had IgM and IgA antibodies. A correlation was observed for the presence of antibodies in serum, cord blood, and breast milk.
There were 15 babies without detectable IgG antibodies, almost all of whom were born to infected mothers within a month of delivery. In addition, nearly 90% of these babies were born to seronegative mothers, and most of the remaining babies were born to mothers with IgG in their blood.
Similarly, about 67% of IgA-positive mothers had IgA in their breast milk, while about 75% of negative IgA mothers did not have detectable IgA titers in serum or breast milk. These findings indicate a close correlation between IgA levels in blood and breast milk.
IgG anti-spike were the most common antibodies identified in maternal serum and were therefore higher than IgA and IgM levels. Comparatively, in breast milk, IgA levels were much higher compared to IgM and IgG levels.
In fetal blood, IgG was found in almost 80% of the samples; however, other classes of antibodies were uncommon. On average, IgG levels in fetal blood were about 25% of the value observed in maternal blood.
Symptomatic women and their babies showed serum antibody levels three to five times higher.
Of the three babies who tested positive for COVID-19, only one tested positive at birth and was born to a seronegative mother who was ill at the time. The other two were positive at 15 days of birth.
Cord blood IgG was found in only one infant whose mother was HIV-positive for all three Ig classes at the time. At six months, both mother and baby were HIV-positive.
In two cord blood samples, IgM levels were low, while IgA was low in three samples. All five samples were obtained from infants who were negative for COVID-19 but who had high IgG antibodies against the ear.
Of the matched samples, IgG levels remained high in most women at six months; however, about 33% of mothers showed a significant decrease in their IgM levels to 25% of those reported at birth. IgG levels decreased during this period in 23 of the babies from over 400 to one.
Antibodies were also correlated with blockade of spike-ACE2 receptor binding to maternal serum and cord blood, as well as to breast milk. At six months, this antibody activity persisted at a higher level.
Conclusions
Anti-SARS-CoV-2 antibodies are generated by most pregnant women after infection and can be detected in both breast serum and breast milk. These antibody levels are higher in mothers who experienced a symptomatic infection compared to asymptomatic patients.
The placenta allows for rapid and efficient transfer of IgG to the baby; however, IgG levels decreased significantly over time. In contrast, antibody titers increased in mothers. Antibody titers were also correlated with neutralizing antibody titers, with the strength of the correlation improving over time.
Overall, neonatal passive immunity is conferred by maternal antibody transfer, which is more efficient when infection occurs before pregnancy compared to during the peripartum period. Disruption of antibody glycosylation, which is induced by SARS-CoV-2, may reduce the extent of this 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 does not always indicate that they were infected at that time. In particular, mothers with very low antibody levels were diagnosed near the time of delivery, and most babies born to these mothers were 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 timing of maternal vaccination is not optimal for neonatal immunity, the COVID-19 vaccine will protect the mother from serious illness and adverse pregnancy outcomes.
Antibodies from breast milk can also prevent vertical transmission during breastfeeding. This effect is mediated by secretory IgA (sIgA) from intestinal-associated lymphoid tissue (GALT), which binds to the Ig receptor to enter breast milk by secretion. These elevated titers with accompanied 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, newborns may be passively immunized against SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies. “
Magazine reference:
- Martin-Vicente, M., Carrasco, I., Muñoz-Gomez, MJ, et al. (2022). Antibody levels in the SARS-Cov-2 Spike protein in mothers and children from birth to six months later. Birth. doi: 10.1111 / birt.12667.