Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

Abstract

There is a persistent male bias in the prevalence and severity of COVID-19 disease. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of disease in adults, and play a key role in the placental anti-viral response. Moreover, the interferon response has been shown to alter Fc-receptor expression, and therefore may impact placental antibody transfer. Here we examined the intersection of viral-induced placental interferon responses, maternal-fetal antibody transfer, and fetal sex. Placental interferon stimulated genes (ISGs), Fc-receptor expression, and SARS-CoV-2 antibody transfer were interrogated in 68 pregnancies. Sexually dimorphic placental expression of ISGs, interleukin-10, and Fc receptors was observed following maternal SARS-CoV-2 infection, with upregulation in males. Reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were noted in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study

“…In the setting of third-trimester maternal SARS-CoV-2 infection, relatively low placental transfer ratios were previously reported, possibly relating to an altered antibody glycosylation profile [ 29 ], but we observed higher and satisfactory maternofetal antibody transfer. In addition, although mothers with COVID-19 carrying a male fetus were shown by Bordt et al to exhibit a diminished immune response and compromised neonatal seroprotection [ 30 ], this was not observed in our cohort following maternal vaccination. Furthermore, the lack of detrimental effect of maternal anthropometric parameters and the prenatal administration of anti-D immunoglobulin, on the level of anti-SARS-CoV-2 antibodies conveyed to the offspring are reassuring findings.…”

Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels

“…While in the setting of third-trimester maternal SARS-CoV-2 infection relatively low placental transfer ratios were previously reported, possibly relating to an altered antibody glycosylation profile [29], we observed higher and satisfactory maternofetal antibody transfer. In addition, although mothers with COVID-19 carrying a male fetus were shown by Bordt et al to exhibit a diminished immune response and compromised neonatal seroprotection [30], this was not observed in our cohort following maternal vaccination. Furthermore, the lack of detrimental effect of maternal anthropometric parameters and the prenatal administration of anti-D immunoglobulin, on the level of anti-SARS-CoV-2 antibodies conveyed to the offspring are other reassuring findings.…”

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

“…Reduced placental transfer of SARS-CoV-2-specific immunoglobulin has been observed previously 26 , possibly due to altered glycosylation 27 . Furthermore, reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were also noted in pregnancies with a male fetus 28 , although there did not appear to be any sex bias in our dataset. It is currently unclear whether antibodies induced via vaccination, as opposed to natural infection, differ in terms of their glycosylation status and subsequent placental transfer, which is an important area of research.…”