Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

Bordt, Evan A.; Shook, Lydia L.; Atyeo, Caroline; Pullen, Krista M.; Guzman, Rose M. De; Meinsohn, Marie-Charlotte; Chauvin, Maëva; Fischinger, Stephanie; Yockey, Laura J.; James, Kaitlyn; Lima, Rosiane; Yonker, Lael M.; Fasano, Alessio; Brigida, Sara; Bebell, Lisa M.; Roberts, Drucilla J.; Pépin, David; Huh, Jun R.; Bilbo, Staci D.; Li, Jonathan Z.; Kaimal, Anjali J; Schust, Danny J.; Gray, Kathryn J.; Lauffenburger, Douglas A.; Alter, Galit; Edlow, Andrea G.

doi:10.1126/scitranslmed.abi7428

Cited by 100 publications

(90 citation statements)

References 124 publications

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“…By quantifying anti-SARS-CoV-2 antibody titers and functions in the maternal and cord blood sera, the authors found that the mothers carrying male fetuses had lower maternal and cord blood titers than mothers carrying female pregnancies. Moreover, the transplacental transfer of IgG against other infectious agents, including influenza and pertussis, was not affected in male versus female pregnancies ( 95 ). No evidence of SARS-CoV-2-specific IgM in newborns was reported, supporting that vertical transmission of SARS-CoV-2 is uncommon ( 94 – 96 ).…”

Section: Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-cov-2)...mentioning

confidence: 99%

Effects of Vertical Transmission of Respiratory Viruses to the Offspring

et al. 2022

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Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure in utero is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.

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Section: Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-cov-2)...mentioning

confidence: 99%

Effects of Vertical Transmission of Respiratory Viruses to the Offspring

et al. 2022

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“…In translational work by Bordt et al, mothers carrying male fetuses had lower maternal IgG antibodies and transfer ratio following SARS-CoV-2 infection than pregnancies with female fetuses 18 . The possibility that fetal sex modifies maternal antibody response or placental transfer is intriguing.…”

Section: Discussionmentioning

confidence: 95%

Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

Otero

Sunderraj

Shanes

et al. 2022

Preprint

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Background: Pregnant persons are at increased risk of severe COVID-19 and adverse obstetric outcomes. Understanding maternal antibody response and transplacental transfer after SARS-CoV-2 infection and COVID-19 vaccination is important to inform public health recommendations. Methods: This prospective observational cohort study included 351 birthing individuals who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. IgG and IgM to SARS-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across 1) disease severity for those with SARS-CoV-2 infection and 2) infection versus vaccination. Findings: There were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection category had higher maternal and cord blood IgG levels (p=0.0001, p=0.0001). Median IgG transfer ratio was 0.87-1.2. Maternal and cord blood IgG were higher after vaccination than infection (p=0.001, p=0.001). Transfer ratio was higher after 90 days in the vaccinated group (p<0.001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (p<0.0001). There were no significant differences by fetal sex. Interpretation: COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG levels, higher cord blood IgG, and higher transfer ratio after 90 days compared to SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.

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“…CXCL10 (C-X-C motif chemokine ligand 10) is a pro-inflammatory chemokine secreted in response to interferon gamma (IFNγ) involved in the stimulation of monocytes, natural killer, and T-cells. Previous investigations have also reported CXCL10 gene expression upregulation in bronchoalveolar lavages [57], nasopharyngeal swabs [58] and male placentas exposed to maternal SARS-CoV-2 infection [43]. Importantly, CXCL10 may also be a key regulator of the “cytokine storm” in response to SARS-CoV-2 infection and circulating levels of CXCL10 are reported to be positively associated with disease severity [59-61].…”

Section: Discussionmentioning

confidence: 97%

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes

Lesseur

Jessel

Ohrn

et al. 2022

Preprint

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Introduction: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. Methods: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher exact tests, Spearman correlations and linear regression models. Results: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. Discussion: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.

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Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses

Abstract: Maternal SARS-CoV-2 infection drives sexually dimorphic placental immune responses and reduces SARS-CoV-2–specific antibody transfer to male fetuses.

Cited by 100 publications

References 124 publications

Effects of Vertical Transmission of Respiratory Viruses to the Offspring

Effects of Vertical Transmission of Respiratory Viruses to the Offspring

Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes

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