Studies Reveal Antibody Responses of Pregnant Women Infected with SARS-CoV-2

Two recently published studies were effective in determining the antibody responses of pregnant women infected with SARS-CoV-2 and the effect of the fetal sex on those responses. They also found direct clinical implications for COVID-19 infection, as well as future maternal-fetal vaccination strategies.

One of the studies involved a systems serology approach to phenotype the anti- SARS-CoV-2 antibodies in the sera of pregnant, nonpregnant and lactating women following administration of mRNA-1273 or BNT162b2 COVID-19 vaccines. Results indicated pregnant women showed lower SARS-CoV-2 antibody titers, restricted IgG subclass responses and a decreased FcR-binding capacity following the first dose of the vaccine compared to nonpregnant women. However, minimal differences were observed after the second dose between pregnant and lactating women and nonpregnant women. Only in lactating women, increased natural killer (NK) cell-activating antibodies were observed following the second dose of vaccination.

Differences in responses to each mRNA vaccine formulation were also observed in pregnant women. For the mRNA-1237 vaccine, immune responses were enriched for neutrophil and NK cell-recruiting antibodies. In contrast, for the BNT162b2 vaccine, they were more enriched for less specific IgG1 and FcRYIIIa-binding antibodies.

Concerning passive immunity, higher SARS-CoV-2 antibodies were observed in maternal sera compared to cord sera, most likely due to immunization at a later stage of the pregnancy. Additionally, this reduction in transfer may be due to a lower abundance of FcRYIIIa-binding antibodies in pregnant women. However, in lactating women, higher antibodies with greater functional and FcR-binding qualities were observed after vaccination.

The other study investigated the antibody and antiviral interferon responses in COVID-19-infected and -uninfected pregnant women and whether the sex of the fetus had an impact on those responses. To determine the effect of fetal sex on the antibody response, the anti-SARS-CoV-2 antibody titers were quantified along with functions and specificities in maternal and cord blood sera of pregnancies with female and male fetuses.

Results indicated mothers carrying male fetuses had lower titers of IgG antibodies for all SARS-CoV-2-specific antigens. This suggests the fetal sex affects the maternal antibody responses. Furthermore, the transfer ratio of SARS-CoV-2 antibodies was lower in cord blood for male pregnancies compared to female pregnancies.

Placental staining and genome analyses were also conducted to determine whether sex-specific differences in placental FcR expression existed. Results indicated an increased expression of FcRn, FcRYII and FcYRIII, as well as increased co-localization of FcRn and FcRYIII in the male-derived placenta. Glycan profiling revealed that in male pregnancies, higher titers of antibodies were modified by glycosylation and fucosylation. Fucosylated antibodies are less efficiently transferred by the FcRYIIIa-binding that explains the lower IgG transfer in male pregnancies.

According to the researchers, the studies emphasize the need for incorporating pregnant women at different stages of gestation in clinical trials for the development of vaccines.