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1.
Nat Commun ; 13(1): 320, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1632529

ABSTRACT

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.


Subject(s)
COVID-19/immunology , Immunity/immunology , Infectious Disease Transmission, Vertical , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , COVID-19/blood , COVID-19/virology , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant, Newborn , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Young Adult
2.
J Reprod Immunol ; 149: 103464, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561228

ABSTRACT

We studied the T cell response to SARS-CoV-2 spike and non-spike peptide epitopes in eight convalescent pregnant women together with the immune monitoring that included innate tolerogenic dendritic cell populations important to maintain the immunological mother/fetus interface to address a potential risk for the antiviral cellular response in the outcome of pregnancy. Four subjects had pre-existing chronic inflammatory conditions that could have potentially affected the SARS-CoV-2-specific T cell response. Seven of eight subjects responded to SARS-CoV-2 peptides with differences within CD4+ T helper (Th) and CD8+ cytotoxic T cells (CTL). SARS-CoV-2-specific inducible regulatory T cells (iTreg) were numerous in circulation. CD4+ T cell memory included central memory T cells (TCM) and effector memory (TEM). As far as the CD8+ memory repertoire, TCM and TEM were very low or absent in eight of eight subjects and only effector cells that revert to CD45RA+, defined as TEMRA were measurable in circulation. T cells were in the normal range in all subjects regardless of pre-existing inflammatory conditions. The immune phenotype indicated the expansion and activation of tolerogenic myeloid dendritic cells including CD14+ cDC2 and CD4+ ILT-4+ tmDC. In summary, SARS-CoV-2 infection induced a physiological anti-viral T cell response in pregnant women that included SARS-CoV-2-specific iTreg with no negative effects on the tolerogenic innate dendritic cell repertoire relevant to the immune homeostasis of the maternal-fetal interface. All eight subjects studied delivered full-term, healthy infants.


Subject(s)
COVID-19/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Female , Humans , Pregnancy , Prospective Studies
3.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166285, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1460712

ABSTRACT

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.


Subject(s)
COVID-19/etiology , COVID-19/transmission , Mycoplasma Infections/etiology , Mycoplasma Infections/transmission , Pregnancy Complications, Infectious , Zika Virus Infection/etiology , Zika Virus Infection/transmission , Biomarkers , Breast Feeding/adverse effects , Disease Susceptibility , Female , Host-Pathogen Interactions/immunology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Maternal-Fetal Exchange , Mycoplasma , Placenta/immunology , Placenta/metabolism , Placenta/microbiology , Placenta/virology , Pregnancy , SARS-CoV-2 , Zika Virus
4.
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
5.
Int J Mol Sci ; 22(6)2021 Mar 13.
Article in English | MEDLINE | ID: covidwho-1389393

ABSTRACT

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.


Subject(s)
Immunity , Placenta/immunology , Placenta/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Virus Diseases/immunology , Viruses/immunology , Female , Fetus/immunology , Fetus/virology , Humans , Placenta/pathology , Pregnancy , Trophoblasts/immunology , Trophoblasts/virology
6.
Reprod Toxicol ; 104: 134-142, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331182

ABSTRACT

AZD1222 (ChAdOx1 nCoV-19) is a COVID-19 vaccine that is not yet licensed for use during pregnancy. To support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies, a non-clinical developmental and reproductive toxicity study was performed to evaluate its effects on fertility and reproductive processes of female CD-1 mice during the embryofetal development phase, and postnatal outcomes during the littering phase. Immunogenicity assessments were also made in dams, fetuses, and pups. There were no vaccine-related unscheduled deaths throughout the study. Furthermore, there were no vaccine-related effects on female reproduction, fetal or pup survival, fetal external, visceral, or skeletal findings, pup physical development, and no abnormal gross pathology findings in pups or dams. Antibody responses raised in dams were maintained throughout gestation and postnatal periods, and seroconversion in fetuses and pups indicate placental and lactational transfer of immunoglobulins. Together with clinical data from non-pregnant people, these results support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , Immunogenicity, Vaccine , Vaccination , Animals , Biomarkers/blood , COVID-19 Vaccines/toxicity , Female , Fetus/drug effects , Fetus/immunology , Fetus/metabolism , Gestational Age , Lactation/immunology , Lactation/metabolism , Maternal-Fetal Exchange , Mice , Placenta/immunology , Placenta/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Risk Assessment , Seroconversion
7.
Cell Prolif ; 54(9): e13091, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1320384

ABSTRACT

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.


Subject(s)
Cytokines/analysis , Placenta/virology , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Viral Proteins/isolation & purification , Adult , Amniotic Fluid/chemistry , COVID-19/pathology , Female , Fetal Blood/chemistry , Humans , Infant, Newborn , Macrophages/immunology , Nucleic Acid Amplification Techniques , Placenta/immunology , Pregnancy , RNA, Viral/blood , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Viral Proteins/blood
8.
Front Immunol ; 12: 698578, 2021.
Article in English | MEDLINE | ID: covidwho-1278398

ABSTRACT

Pregnant women have been carefully observed during the COVID-19 pandemic, as the pregnancy-specific immune adaptation is known to increase the risk for infections. Recent evidence indicates that even though most pregnant have a mild or asymptomatic course, a severe course of COVID-19 and a higher risk of progression to diseases have also been described, along with a heightened risk for pregnancy complications. Yet, vertical transmission of the virus is rare and the possibility of placental SARS-CoV-2 infection as a prerequisite for vertical transmission requires further studies. We here assessed the severity of COVID-19 and onset of neonatal infections in an observational study of women infected with SARS-CoV-2 during pregnancy. Our placental analyses showed a paucity of SARS-CoV-2 viral expression ex vivo in term placentae under acute infection. No viral placental expression was detectable in convalescent pregnant women. Inoculation of placental explants generated from placentas of non-infected women at birth with SARS-CoV-2 in vitro revealed inefficient SARS-CoV-2 replication in different types of placental tissues, which provides a rationale for the low ex vivo viral expression. We further detected specific SARS-CoV-2 T cell responses in pregnant women within a few days upon infection, which was undetectable in cord blood. Our present findings confirm that vertical transmission of SARS-CoV-2 is rare, likely due to the inefficient virus replication in placental tissues. Despite the predominantly benign course of infection in most mothers and negligible risk of vertical transmission, continuous vigilance on the consequences of COVID-19 during pregnancy is required, since the maternal immune activation in response to the SARS-CoV2 infection may have long-term consequences for children's health.


Subject(s)
COVID-19/immunology , COVID-19/transmission , Infectious Disease Transmission, Vertical , Placenta/virology , Pregnancy Complications, Infectious/immunology , Adult , Female , Fetal Blood/immunology , Humans , Infant, Newborn , Middle Aged , Placenta/immunology , Pregnancy , SARS-CoV-2/immunology , Virus Replication/physiology
9.
Int J Mol Sci ; 22(11)2021 May 28.
Article in English | MEDLINE | ID: covidwho-1256562

ABSTRACT

A pandemic of acute respiratory infections, due to a new type of coronavirus, can cause Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) and has created the need for a better understanding of the clinical, epidemiological, and pathological features of COVID-19, especially in high-risk groups, such as pregnant women. Viral infections in pregnant women may have a much more severe course, and result in an increase in the rate of complications, including spontaneous abortion, stillbirth, and premature birth-which may cause long-term consequences in the offspring. In this review, we focus on the mother-fetal-placenta interface and its role in the potential transmission of SARS-CoV-2, including expression of viral receptors and proteases, placental pathology, and the presence of the virus in neonatal tissues and fluids. This review summarizes the current knowledge on the anti-viral activity of lactoferrin during viral infection in pregnant women, analyzes its role in the pathogenicity of pandemic virus particles, and describes the potential evidence for placental blocking/limiting of the transmission of the virus.


Subject(s)
Anti-Infective Agents/pharmacology , COVID-19/immunology , Infectious Disease Transmission, Vertical/prevention & control , Lactoferrin/pharmacology , Placenta/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , COVID-19/complications , Female , Humans , Infant, Newborn , Lactoferrin/metabolism , Placenta/pathology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/immunology
10.
Neuroimmunomodulation ; 28(1): 1-21, 2021.
Article in English | MEDLINE | ID: covidwho-1206095

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has devastating effects on the population worldwide. Given this scenario, the extent of the impact of the disease on more vulnerable individuals, such as pregnant women, is of great concern. Although pregnancy may be a risk factor in respiratory virus infections, there are no considerable differences regarding COVID-19 severity observed between pregnant and nonpregnant women. In these circumstances, an emergent concern is the possibility of neurodevelopmental and neuropsychiatric harm for the offspring of infected mothers. Currently, there is no stronger evidence indicating vertical transmission of SARS-CoV-2; however, the exacerbated inflammatory response observed in the disease could lead to several impairments in the offspring's brain. Furthermore, in the face of historical knowledge on possible long-term consequences for the progeny's brain after infection by viruses, we must consider that this might be another deleterious facet of COVID-19. In light of neuroimmune interactions at the maternal-fetal interface, we review here the possible harmful outcomes to the offspring brains of mothers infected by SARS-CoV-2.


Subject(s)
COVID-19/immunology , Neurodevelopmental Disorders/physiopathology , Neuroimmunomodulation/immunology , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/physiopathology , COVID-19/metabolism , COVID-19/physiopathology , Cytokine Release Syndrome/immunology , Decidua/immunology , Female , Humans , Immune Tolerance/immunology , Infectious Disease Transmission, Vertical , Neuroimmunomodulation/physiology , Placenta/immunology , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2 , Umbilical Cord/immunology
12.
Front Immunol ; 12: 631044, 2021.
Article in English | MEDLINE | ID: covidwho-1094169

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID-19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.


Subject(s)
B-Lymphocytes/immunology , COVID-19/immunology , Fetal Blood/immunology , Germinal Center/immunology , Placenta/immunology , SARS-CoV-2/physiology , Th17 Cells/immunology , Angiotensin-Converting Enzyme 2/metabolism , Autoantigens/metabolism , Female , Flow Cytometry , Humans , Immunologic Memory , Immunophenotyping , Killer Cells, Natural , Pregnancy , Receptors, Interleukin-1/metabolism , Serine Endopeptidases/metabolism
13.
J Med Virol ; 93(5): 2769-2773, 2021 May.
Article in English | MEDLINE | ID: covidwho-1070767

ABSTRACT

The coronavirus disease 2019 (COVID-19), which had spread to the world from Wuhan (China) in late December, was announced as a pandemic by the World Health Organization in March 2020. In addition to acute respiratory syndrome symptoms, this virus also affects nonrespiratory organs, according to existing data. ACE2 and TMPRSS2, which play a critical role in the entrance of SARS-COV-2 into the cell, are coexpressed in placental development stages, so the placenta also carries a risk for this virus. Many studies have shown that this virus causes some histopathological changes in the placenta. The vertical transmission of the virus is not yet clear, but available data have shown that the indirect effects of the virus can be seen on the fetus. This article focuses on revealing the effects of the virus on the placenta in all aspects.


Subject(s)
COVID-19/epidemiology , Placenta/virology , Pregnancy Complications, Infectious/epidemiology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , COVID-19/therapy , COVID-19/transmission , Cytokine Release Syndrome/immunology , Female , Humans , Infectious Disease Transmission, Vertical , Placenta/cytology , Placenta/immunology , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/immunology , SARS-CoV-2 , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Stem Cell Transplantation
14.
Early Hum Dev ; 155: 105322, 2021 04.
Article in English | MEDLINE | ID: covidwho-1053333

ABSTRACT

From the moment of the identification of SARS-CoV-2 as an etiological agent of the severe clinical pictures of pneumonia that were being slowly observed all over the world, numerous studies have been conducted to increase the knowledge about what was an unknown virus until then. The efforts were mainly aimed to acquire epidemiological, microbiological, pathogenetic, clinical, diagnostic, therapeutic and preventive information in order to increase the available weapons to fight an infection which was rapidly taking on the characteristics of the pandemic. Given the topicality of the problem, not everything has yet been fully understood and clarified, especially in the maternal-fetal­neonatal field, where we are beginning to question what could be the outcomes of newborn babies born to mothers who contracted SARS-CoV-2 infection during pregnancy. Thus, the aim of this review is to analyze the long-term outcomes of this infection that could affect the offspring, regardless of a possible maternal-fetal transmission, focusing on, above all, the role of maternal immune activation and the expression of the Angiotensin-converting enzyme 2 (ACE2) in particular at the placental level.


Subject(s)
COVID-19/complications , Infant, Newborn, Diseases/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Adaptive Immunity , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , COVID-19/therapy , COVID-19/transmission , Female , Fetal Development , Humans , Infant, Newborn , Infant, Newborn, Diseases/embryology , Infant, Newborn, Diseases/metabolism , Infectious Disease Transmission, Vertical , Placenta/immunology , Placenta/metabolism , Pregnancy , Time Factors
15.
J Virol ; 95(2)2020 12 22.
Article in English | MEDLINE | ID: covidwho-1041542

ABSTRACT

Viral infections during pregnancy lead to a spectrum of maternal and fetal outcomes, ranging from asymptomatic disease to more critical conditions presenting with severe maternal morbidity, stillbirth, preterm birth, intrauterine growth restriction, and fetal congenital anomalies, either apparent at birth or later in life. In this article, we review the pathogenesis of several viral infections that are particularly relevant in the context of pregnancy and intrauterine inflammation. Understanding the diverse mechanisms employed by viral pathogens as well as the repertoire of immune responses induced in the mother may help to establish novel therapeutic options to attenuate changes in the maternal-fetal interface and prevent adverse pregnancy outcomes.


Subject(s)
Inflammation/immunology , Pregnancy Complications, Infectious/virology , Virus Diseases/virology , Viruses/pathogenicity , Female , Humans , Infant, Newborn , Placenta/immunology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Virus Diseases/immunology , Virus Diseases/pathology , Viruses/classification , Viruses/immunology
16.
Front Immunol ; 11: 572567, 2020.
Article in English | MEDLINE | ID: covidwho-886164

ABSTRACT

Immunological adaptations in pregnancy allow maternal tolerance of the semi-allogeneic fetus but also increase maternal susceptibility to infection. At implantation, the endometrial stroma, glands, arteries and immune cells undergo anatomical and functional transformation to create the decidua, the specialized secretory endometrium of pregnancy. The maternal decidua and the invading fetal trophoblast constitute a dynamic junction that facilitates a complex immunological dialogue between the two. The decidual and peripheral immune systems together assume a pivotal role in regulating the critical balance between tolerance and defense against infection. Throughout pregnancy, this equilibrium is repeatedly subjected to microbial challenge. Acute viral infection in pregnancy is associated with a wide spectrum of adverse consequences for both mother and fetus. Vertical transmission from mother to fetus can cause developmental anomalies, growth restriction, preterm birth and stillbirth, while the mother is predisposed to heightened morbidity and maternal death. A rapid, effective response to invasive pathogens is therefore essential in order to avoid overwhelming maternal infection and consequent fetal compromise. This sentinel response is mediated by the innate immune system: a heritable, highly evolutionarily conserved system comprising physical barriers, antimicrobial peptides (AMP) and a variety of immune cells-principally neutrophils, macrophages, dendritic cells, and natural killer cells-which express pattern-receptors that detect invariant molecular signatures unique to pathogenic micro-organisms. Recognition of these signatures during acute infection triggers signaling cascades that enhance antimicrobial properties such as phagocytosis, secretion of pro-inflammatory cytokines and activation of the complement system. As well as coordinating the initial immune response, macrophages and dendritic cells present microbial antigens to lymphocytes, initiating and influencing the development of specific, long-lasting adaptive immunity. Despite extensive progress in unraveling the immunological adaptations of pregnancy, pregnant women remain particularly susceptible to certain acute viral infections and continue to experience mortality rates equivalent to those observed in pandemics several decades ago. Here, we focus specifically on the pregnancy-induced vulnerabilities in innate immunity that contribute to the disproportionately high maternal mortality observed in the following acute viral infections: Lassa fever, Ebola virus disease (EVD), dengue fever, hepatitis E, influenza, and novel coronavirus infections.


Subject(s)
Decidua/immunology , Placenta/immunology , Virus Diseases/immunology , Adaptive Immunity/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Dengue/immunology , Dengue/pathology , Female , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/pathology , Hepatitis E/immunology , Hepatitis E/pathology , Humans , Immune Tolerance/immunology , Immunity, Innate/immunology , Influenza, Human/immunology , Influenza, Human/pathology , Lassa Fever/immunology , Lassa Fever/pathology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pregnancy
17.
Am J Reprod Immunol ; 84(5): e13306, 2020 11.
Article in English | MEDLINE | ID: covidwho-708944

ABSTRACT

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to host inflammatory response.2 Despite rapid, global research, the effect of SARS-CoV-2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3-7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS-CoV-2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long-term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS-CoV-2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.


Subject(s)
COVID-19/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy , Prenatal Exposure Delayed Effects/immunology , SARS-CoV-2/physiology , COVID-19/transmission , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pandemics , Placenta/virology
18.
Cells ; 9(8)2020 07 25.
Article in English | MEDLINE | ID: covidwho-698553

ABSTRACT

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic has caused a global public health crisis. Viral infections may predispose pregnant women to a higher rate of pregnancy complications, including preterm births, miscarriage, and stillbirth. Despite reports of neonatal COVID-19, definitive proof of vertical transmission is still lacking. In this review, we summarize studies regarding the potential evidence for transplacental transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterize the expression of its receptors and proteases, describe the placental pathology and analyze virus-host interactions at the maternal-fetal interface. We focus on the syncytium, the barrier between mother and fetus, and describe in detail its physical and structural defense against viral infections. We further discuss the potential molecular mechanisms, whereby the placenta serves as a defense front against pathogens by regulating the interferon type III signaling, microRNA-triggered autophagy and the nuclear factor-κB pathway. Based on these data, we conclude that vertical transmission may occur but rare, ascribed to the potent physical barrier, the fine-regulated placental immune defense and modulation strategies. Particularly, immunomodulatory mechanisms employed by the placenta may mitigate violent immune response, maybe soften cytokine storm tightly associated with severely ill COVID-19 patients, possibly minimizing cell and tissue damages, and potentially reducing SARS-CoV-2 transmission.


Subject(s)
Coronavirus Infections/transmission , Infectious Disease Transmission, Vertical , Placenta/immunology , Placenta/virology , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious/immunology , Autophagy/immunology , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Infant, Newborn , MicroRNAs/genetics , MicroRNAs/metabolism , Pandemics , Placenta/metabolism , Placenta/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/virology , SARS-CoV-2
19.
Am J Reprod Immunol ; 84(5): e13308, 2020 11.
Article in English | MEDLINE | ID: covidwho-654180

ABSTRACT

Coronavirus disease 2019 or COVID-19 is an emerging viral disease caused by a member of the betacoronavirus family, SARS-CoV-2. Since its' emergence in December 2019, it has rapidly caused close to half a million fatalities globally. Data regarding the impact of COVID-19 on pregnancy are limited. Here, we review pathological findings in placentas from women who tested positive for SARS-CoV-2 as well as information on pregnancy outcomes associated with related and highly pathogenic coronaviruses (ie, severe acute respiratory syndrome (SARS-COV) and the Middle East respiratory syndrome, MERS). We present immune-inflammatory correlates of COVID-19 in pregnancy and review the role of the Renin Angiotensin System in the pathogenesis of COVID-19 in pregnancy. Greater understanding of the pathogenesis of SARS-CoV-2 in the placenta will yield important insight into potential therapeutic interventions for pregnant women with COVID-19.


Subject(s)
COVID-19/metabolism , Placenta/immunology , Pregnancy Complications, Infectious/metabolism , Pregnancy , Renin-Angiotensin System/physiology , SARS-CoV-2/physiology , COVID-19/immunology , COVID-19/virology , Female , Humans , Pandemics , Placenta/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome
20.
Eur J Obstet Gynecol Reprod Biol ; 252: 605-609, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-625606

ABSTRACT

This review evaluates whether pregnancy is a risk factor for COVID-19 by looking at the expression of immune markers such as immune cells and cytokines in order to have a better understanding on the pathophysiology of the disease, thus reducing maternal deaths. Pregnant women are more at risk of contracting COVID-19 due to their weakened immune system. Studies demonstrate that COVID-19 is an immune condition which is marked by reduced lymphocytes and elevated selected proinflammatory cytokines. Similar immune expression has been demonstrated in pregnancy by several studies. In addition, the placenta has been shown to possess ACE2 receptors on the villous cytotrophoblast and the syncytiotrophoblast and findings suggest that the coronavirus enters the host cells via these ACE2 receptors. The immune response in pregnancy increases the risk of contracting COVID-19. Both normal pregnancy and COVID-19 are marked by decreased lymphocytes, NKG2A inhibitory receptors, and increased ACE2, IL-8, IL-10, and IP-10 it therefore safer to conclude that pregnancy is a risk factor for COVID-19 development. Furthermore, the presence of the ACE2 receptors in the placenta may increase the risk of mother to baby transmission of the virus. Therefore, more studies investigating the link between pregnancy and COVID-19 are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Pregnancy Complications, Infectious/immunology , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cytokines/blood , Female , Humans , Infectious Disease Transmission, Vertical , Pandemics , Peptidyl-Dipeptidase A/immunology , Placenta/immunology , Placenta/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , Risk Factors , SARS-CoV-2
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