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1.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1877125

ABSTRACT

Early life adversity can significantly impact child development and health outcomes throughout the life course. With the COVID-19 pandemic exacerbating preexisting and introducing new sources of toxic stress, social programs that foster resilience are more necessary now than ever. The Helping Us Grow Stronger (HUGS/Abrazos) program fills a crucial need for protective buffers during the COVID-19 pandemic, which has escalated toxic stressors affecting pregnant women and families with young children. HUGS/Abrazos combines patient navigation, behavioral health support, and innovative tools to ameliorate these heightened toxic stressors. We used a mixed-methods approach, guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, to evaluate the implementation of the HUGS/Abrazos program at Massachusetts General Hospital from 6/30/2020–8/31/2021. Results of the quality improvement evaluation revealed that the program was widely adopted across the hospital and 392 unique families were referred to the program. The referred patients were representative of the communities in Massachusetts disproportionately affected by the COVID-19 pandemic. Furthermore, 79% of referred patients followed up with the initial referral, with sustained high participation rates throughout the program course;and they were provided with an average of four community resource referrals. Adoption and implementation of the key components in HUGS/Abrazos were found to be appropriate and acceptable. Furthermore, the implemented program remained consistent to the original design. Overall, HUGS/Abrazos was well adopted as an emergency relief program with strong post-COVID-19 applicability to ameliorate continuing toxic stressors while decreasing burden on the health system.

2.
Am J Obstet Gynecol ; 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1872911

ABSTRACT

BACKGROUND: SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the Centers for Disease Control and Prevention and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns, including the Omicron variant, raised new concerns about vaccine efficacy because of their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following infection with the Omicron variant in vaccinated individuals. Thus, these data suggest that alternate vaccine-induced immunity beyond neutralization may continue to attenuate Omicron variant-induced disease, such as Fc-mediated antibody activity. OBJECTIVE: This study aimed to test whether vaccine-induced antibodies raised during pregnancy continue to bind to and leverage Fc receptors to protect against variants of concern including the Omicron variant. STUDY DESIGN: The receptor binding domain or whole spike-specific antibody isotype binding titers and Fc gamma receptor binding directed toward variants of concern, including the Omicron variant, were analyzed in pregnant women after receiving the full dose regimen of either the Pfizer/BioNTech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay. RESULTS: Reduced isotype recognition of the Omicron receptor binding domain was observed following administration of either vaccine with relatively preserved, albeit reduced, recognition of the whole Omicron spike by immunoglobulin M and G antibodies. Despite the near complete loss of Fc receptor binding to the Omicron receptor binding domain, Fc receptor binding to the Omicron spike was more variable but largely preserved. CONCLUSION: Reduced binding titers to the Omicron receptor binding domain aligns with the observed loss of neutralizing activity. Despite the loss of neutralization, preserved, albeit reduced, Omicron spike recognition and Fc receptor binding potentially continue to attenuate disease severity in pregnant women.

3.
Vaccines (Basel) ; 10(4)2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1822452

ABSTRACT

Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. We tested the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the SARS-CoV-2 D614G ("wild type") and Omicron antigens. Serum from 77 adolescents showed that anti-Spike antibodies wane significantly over six months. After completion of a two-vaccine series, cross-reactivity against Omicron-specific receptor-binding domain (RBD) was seen. Functional humoral activation against wild type and Omicron SARS-CoV-2 also declines over time in vaccinated adolescent children. Evidence of waning mRNA-induced vaccine immunity underscores vulnerabilities in long-term pediatric protection against SARS-CoV-2 infection, while cross-reactivity highlights the additional benefits of vaccination. Characterization of adolescent immune signatures post-vaccination will inform guidance on vaccine platforms and timelines, and ultimately optimize immunoprotection of children.

5.
Trends Mol Med ; 28(4): 319-330, 2022 04.
Article in English | MEDLINE | ID: covidwho-1740055

ABSTRACT

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to date, given the potential for profound maternal immune activation (MIA), impact on the developing fetal brain is likely. Here we review evidence that SARS-CoV-2 and other viral infections during pregnancy can result in maternal, placental, and fetal immune activation, and ultimately in offspring neurodevelopmental morbidity. Finally, we highlight the need for cellular models of fetal brain development to better understand potential short- and long-term impacts of maternal SARS-CoV-2 infection on the next generation.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Brain , Female , Humans , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , SARS-CoV-2
6.
J Infect Dis ; 225(5): 754-758, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1621621

ABSTRACT

There is limited information on the specific impact of maternal infection with the SARS-CoV-2 B.1.617.2 (delta) variant on pregnancy outcomes. We present 2 cases of intrauterine fetal demise and 1 case of severe fetal distress in the setting of maternal infection with delta-variant SARS-CoV-2. In all cases, fetal demise or distress occurred within 14 days of COVID-19 diagnosis. Evaluation revealed maternal viremia, high nasopharyngeal viral load, evidence of placental infection with delta-variant SARS-CoV-2, and hallmark features of SARS-CoV-2 placentitis. We suggest that delta-variant SARS-CoV-2 infection during pregnancy warrants vigilance for placental dysfunction and fetal compromise regardless of disease severity.


Subject(s)
COVID-19/diagnosis , Fetal Death , Fetal Distress , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Adult , COVID-19/complications , COVID-19/mortality , COVID-19 Testing , Chorioamnionitis , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/diagnosis
7.
J Infect Dis ; 224(Supplement_6): S642-S646, 2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1559852

ABSTRACT

We previously demonstrated that the late gestation placental expression pattern of ACE2 (the primary severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) is localized to the villous syncytiotrophoblast (ST), usually in a polarized membranous pattern at the ST base sparing the apical surface (that directly exposed to maternal blood). We found that the late gestation placental expression pattern of TMPRSS2 (the spike proteinase required for SARS-CoV-2 cellular infection), is usually absent in the trophoblast but is rarely, weakly expressed in the placental endothelium. We now show the developmental protein expression patterns of ACE2 and TMPRSS2 by immunohistochemistry throughout gestation, from the first through third trimester. We found that TMPRSS2 expression was rarely detectable in villous endothelium and very rarely detectable in the ST across gestation. We found that ACE2 expression varied during gestation with circumferential ST expression more common in early gestations and polarized expression more common in later gestation. Although this study is small, these preliminary results suggest that earlier gestation pregnancies may be more vulnerable to infection than later gestation pregnancies.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Placenta/metabolism , Pregnancy Complications, Infectious/virology , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Adult , Angiotensin-Converting Enzyme 2/genetics , Female , Gestational Age , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/pathology , Serine Endopeptidases/genetics , Trophoblasts
8.
J Infect Dis ; 224(Suppl 6): S647-S659, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1559634

ABSTRACT

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , Fetal Blood/immunology , Placenta/metabolism , SARS-CoV-2/immunology , Serine Endopeptidases/metabolism , Sex Factors , Adult , COVID-19/blood , Female , Fetal Blood/virology , Fetus/virology , Gene Expression , Humans , Infectious Disease Transmission, Vertical , Male , Pregnancy , Pregnancy Complications, Infectious/virology
9.
J Infect Dis ; 224(Suppl 6): S660-S669, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1559086

ABSTRACT

BACKGROUND: SARS-CoV-2 infection in term placenta is rare. However, growing evidence suggests that susceptibility of the human placenta to infection may vary by gestational age and pathogen. For several viral infections, susceptibility appears to be greatest during early gestation. Peri-implantation placental infections that result in pre-clinical pregnancy loss would typically go undetected. Little is known about the effects of SARS-CoV-2 on the peri-implantation human placenta since this time in pregnancy can only be modeled in vitro. METHODS: We used a human embryonic stem cell (hESC)-derived model of peri-implantation placental development to assess patterns of ACE2 and TMPRSS2 transcription and protein expression in primitive trophoblast. We then infected the same trophoblast cell model with a clinical isolate of SARS-CoV-2 and documented infection dynamics. RESULTS: ACE2 and TMPRSS2 were transcribed and translated in hESC-derived trophoblast, with preferential expression in syncytialized cells. These same cells supported replicative and persistent infection by SARS-CoV-2, while non-syncytialized trophoblast cells in the same cultures did not. CONCLUSIONS: Co-expression of ACE2 and TMPRSS2 in hESC-derived trophoblast and the robust and replicative infection limited to syncytiotrophoblast equivalents support the hypothesis that increased viral susceptibility may be a defining characteristic of primitive trophoblast.


Subject(s)
COVID-19/diagnosis , Placenta/metabolism , Pregnancy Complications, Infectious/virology , Abortion, Spontaneous/virology , Adult , Angiotensin-Converting Enzyme 2 , COVID-19/blood , Female , Humans , Pregnancy , Risk Factors , SARS-CoV-2 , Serine Endopeptidases , Trophoblasts
10.
Sci Transl Med ; 13(617): eabi8631, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1532951

ABSTRACT

Substantial immunological changes occur throughout pregnancy to render the mother immunologically tolerant to the fetus and allow fetal growth. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against pathogens both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contributes to increased susceptibility to particular infections in pregnancy, including more severe coronavirus disease 2019 (COVID-19). Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To define potential changes in vaccine response during pregnancy and lactation, we undertook deep sequencing of the humoral vaccine response in a group of pregnant and lactating women and nonpregnant age-matched controls. Vaccine-specific titers were comparable between pregnant women, lactating women, and nonpregnant controls. However, Fc receptor (FcR) binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared with nonpregnant women after the first vaccine dose, which normalized after the second dose. Vaccine boosting resulted in high FcR-binding titers in breastmilk. These data suggest that pregnancy promotes resistance to generating proinflammatory antibodies and indicates that there is a critical need to follow prime-boost timelines in this vulnerable population to ensure full immunity is attained.


Subject(s)
COVID-19 Vaccines , COVID-19 , Female , Humans , Lactation , Pregnancy , RNA, Messenger , SARS-CoV-2
11.
Pediatr Res ; 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1506408

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, thousands of pregnant women have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being need to be characterized. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection. METHODS: We performed single-cell RNA-sequencing and T cell receptor sequencing on cord blood mononuclear cells (CBMCs) from newborns of mothers infected with SARS-CoV-2 in the third trimester (cases) or without SARS-CoV-2 infection (controls). RESULTS: We identified widespread gene expression changes in CBMCs from cases, including upregulation of interferon-stimulated genes and major histocompatibility complex genes in CD14+ monocytes, transcriptional changes suggestive of activation of plasmacytoid dendritic cells, and activation and exhaustion of natural killer cells. Lastly, we observed fetal T cell clonal expansion in cases compared to controls. CONCLUSIONS: As none of the infants were infected with SARS-CoV-2, our results suggest that maternal SARS-CoV-2 infection might modulate the fetal immune system in the absence of vertical transmission. IMPACT: The implications of maternal SARS-CoV-2 infection in the absence of vertical transmission on fetal and childhood well-being are poorly understood. Maternal SARS-CoV-2 infection might modulate the fetal immune system in the absence of vertical transmission. This study raises important questions about the untoward effects of maternal SARS-CoV-2 on the fetus, even in the absence of vertical transmission.

12.
Sci Transl Med ; 13(617): eabi7428, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1476378

ABSTRACT

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2­specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Immunity , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , SARS-CoV-2
13.
Am J Perinatol ; 2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1475529

ABSTRACT

Despite evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy, and clear recommendations from professional organizations and the Centers for Disease Control and Prevention (CDC) for pregnant people to get vaccinated, COVID-19 vaccine hesitancy in pregnancy remains a significant public health problem. The emergence of the highly transmissible B.1.617.2 (Delta) variant among primarily unvaccinated people has exposed the cost of vaccine hesitancy. In this commentary, we explore factors contributing to COVID-19 vaccine hesitancy in pregnancy and potential solutions to overcome them. KEY POINTS: · Low COVID-19 vaccination coverage in pregnant people is a major public health problem in the United States.. · COVID-19 vaccine hesitancy in pregnancy is multifactorial.. · The "4 Cs" framework may be useful in countering COVID-19 vaccine hesitancy..

14.
Cell Rep ; 37(6): 109959, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1474393

ABSTRACT

Antibody transfer via breastmilk represents an evolutionary strategy to boost immunity in early life. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been observed in the breastmilk, the functional quality of these antibodies remains unclear. Here, we apply systems serology to characterize SARS-CoV-2-specific antibodies in maternal serum and breastmilk to compare the functional characteristics of antibodies in these fluids. Distinct SARS-CoV-2-specific antibody responses are observed in the serum and breastmilk of lactating individuals previously infected with SARS-CoV-2, with a more dominant transfer of immunoglobulin A (IgA) and IgM into breastmilk. Although IgGs are present in breastmilk, they are functionally attenuated. We observe preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to selective transfer of certain functional antibodies to breastmilk. These data highlight the preferential transfer of SARS-CoV-2-specific IgA and IgM to breastmilk, accompanied by select IgG subpopulations, positioned to create a non-pathologic but protective barrier against coronavirus disease 2019 (COVID-19).


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Milk, Human/immunology , SARS-CoV-2/immunology , Antibody Formation/immunology , Female , Humans , Immunoglobulin Isotypes/immunology , Lactation/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Spike Glycoprotein, Coronavirus/immunology
15.
Front Cell Infect Microbiol ; 11: 735394, 2021.
Article in English | MEDLINE | ID: covidwho-1450801

ABSTRACT

The COVID-19 pandemic has demonstrated the urgent need to develop vaccine strategies optimized for pregnant people and their newborns, as both populations are at risk of developing severe disease. Although not included in COVID-19 vaccine development trials, pregnant people have had access to these vaccines since their initial release in the US and abroad. The rapid development and distribution of novel COVID-19 vaccines to people at risk, including those who are pregnant and lactating, presents an unprecedented opportunity to further our understanding of vaccine-induced immunity in these populations. In this review, we aim to summarize the literature to date on COVID-19 vaccination in pregnancy and lactation and highlight opportunities for investigation that may inform future maternal vaccine development and implementation strategies.


Subject(s)
COVID-19 Vaccines , COVID-19 , Female , Humans , Infant, Newborn , Lactation , Pandemics , Pregnancy , SARS-CoV-2 , Vaccination
16.
Am J Obstet Gynecol ; 225(6): 593.e1-593.e9, 2021 12.
Article in English | MEDLINE | ID: covidwho-1439825

ABSTRACT

Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an increased risk of viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, which can be either placentally mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1% to 3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. The National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in situ hybridization with antisense probe (detects replication) or a sense probe (detects viral messenger RNA) or immunohistochemistry to detect viral nucleocapsid or spike proteins. If the abovementioned methods are not possible, reverse transcription polymerase chain reaction detection or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling and the use of validated reagents and sample protocols (included as appendices).


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Placenta Diseases/diagnosis , Placenta Diseases/virology , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , COVID-19 Nucleic Acid Testing , Consensus , Female , Guidelines as Topic , Humans , Immunohistochemistry , In Situ Hybridization , Microscopy, Electron , National Institute of Child Health and Human Development (U.S.) , Pregnancy , United States/epidemiology
17.
American Journal of Obstetrics and Gynecology ; 224(2):S568-S569, 2021.
Article in English | PMC | ID: covidwho-1384871

ABSTRACT

Objective: Sex differences in the immune response to SARS-CoV-2 infection have been described. ACE2 and TMPRSS2, host cell receptors required for viral entry, are regulated by sex steroids and expressed by trophoblasts. Although vertical transmission of SARS-CoV-2 is rare, how the placenta defends against SARS-CoV-2, and whether there is a sex bias in the risk of vertical transmission, is not well understood. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. Study Design: This is a cohort study of 66 pregnant women (37 SARS-CoV-2 exposed, 29 SARS-CoV-2 unexposed) enrolled on admission to Massachusetts General Hospital from April-June 2020, coincident with universal screening for SARS-CoV-2 infection. SARS-CoV-2 exposure status was determined by nasopharyngeal RT-PCR. Groups were balanced for fetal sex and maternal disease severity. RNA was isolated from placental homogenates and RTqPCR was performed to quantify expression of ACE2 and TMPRSS2 relative to the reference gene YWHAZ, using the 2-(DELTADELTACt) method. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA. Previously determined placental viral loads showed no evidence of SARS-CoV-2 infection in any placentas. Result(s): While there were no fetal sex or SARS-CoV-2 exposure-mediated differences in ACE2 expression (1A), we observed 1.73-fold increased TMPRSS2 expression in SARS-CoV-2 exposed placentas of female offspring compared to female controls (P=0.04, 1B), and 1.84 -fold reduced TMPRSS2 expression in SARS-CoV-2 exposed placentas of male offspring compared to male controls (P=0.0003, 1B). TMPRSS2 expression was significantly higher in placentas of male compared to female offspring in controls (P<0.0001). Conclusion(s): Sexually dimorphic patterns of TMPRSS2 placental gene expression were observed in the setting of maternal SARS-CoV-2 infection, driven by sex differences in TMPRSS2 expression in controls. Implications of these findings for offspring vulnerability to vertical transmission warrants further investigation. [Formula presented]Copyright © 2020

18.
Cell ; 184(3): 628-642.e10, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1385216

ABSTRACT

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Maternal-Fetal Exchange/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Trimester, Third/immunology , Receptors, IgG/immunology , THP-1 Cells
20.
Nat Med ; 27(3): 454-462, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319036

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Age of Onset , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/blood , Antibodies, Viral/analysis , Asymptomatic Infections , COVID-19/blood , COVID-19/pathology , Carrier State/blood , Carrier State/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunity/physiology , Immunoglobulin A/blood , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Young Adult
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