Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.

An Update on COVID-19-Associated Placental Pathologies.

COVID-19 pregnancies are associated with increased rates of premature delivery and stillbirths. It is still a matter of debate whether there is a COVID-19-associated pattern of placenta pathology. We updated our previously published results on a systematic literature review and meta-analysis of COVID-19 pregnancies. In total, 38 reports on 3677 placentas were evaluated regarding histopathological changes. Maternal vascular malperfusion (32%), fetal vascular malperfusion (19%), acute and chronic inflammation (20% and 22%) were frequent pathologies. In non-COVID-19 pregnancies, placentas show similar histologic patterns and mainly similar frequencies of manifestation. It has to be taken into account that there might be an observation bias, because some findings are diagnosed as a "pathology" that might have been classified as minor or unspecific findings in non-COVID-19 placentas. COVID-19 placentitis occurs in 1-2% of cases at the most. In conclusion, this updated meta-analysis indicates that COVID-19 infection during pregnancy does not result in an increased rate of a specific placenta pathology and COVID-19 placentitis is rare.

Late-onset intrauterine growth restriction and HHV-6 infection: A pilot study.

Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections having been associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.

A standardized definition of placental infection by SARS-CoV-2, a consensus statement from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development SARS-CoV-2 Placental Infection Workshop.

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).

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Massive Perivillous Fibrin Deposition in Congenital Cytomegalovirus Infection: A Case Report.

Cytomegalovirus (CMV) infection is one of the most common congenital viral infections. Classically associated placental findings include chronic villitis with plasma cells, stromal hemosiderin deposition, and identification of viral inclusions in villous endothelial and stromal cells. We present a case of confirmed congenital CMV infection that lacked these classical findings, but demonstrated massive perivillous fibrin deposition (MPVFD). This is the first report of CMV associated with MPVFD. MPVFD is an uncommon placental lesion associated with adverse fetal outcomes and a high risk of recurrence. However, the recurrence risk in patients with an infectious cause may be lower in than patients with other associated clinical conditions.

Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection.

Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious congenital defects in the developing fetus. Previous efforts to generate animal models of human ZIKV infection and clinical symptoms often involved manipulating mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced infection and vertical transmission of virus to the embryo. Here, we show that even pregnant mice competent to generate Type I IFN responses that can limit ZIKV infection nonetheless develop profound placental pathology and high frequency of fetal demise. We consistently found that maternal ZIKV exposure led to placental pathology and that ZIKV RNA levels measured in maternal, placental or embryonic tissues were not predictive of the pathological effects seen in the embryos. Placental pathology included trophoblast hyperplasia in the labyrinth, trophoblast giant cell necrosis in the junctional zone, and loss of embryonic vessels. Our findings suggest that, in this context of limited infection, placental pathology rather than embryonic/fetal viral infection may be a stronger contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that in immunocompetent mice, direct viral infection of the embryo is not essential for fetal demise. Our immunologically unmanipulated pregnancy mouse model provides a consistent and easily measurable congenital abnormality readout to assess fetal outcome, and may serve as an additional model to test prophylactic and therapeutic interventions to protect the fetus during pregnancy, and for studying the mechanisms of ZIKV congenital immunopathogenesis.

Placental infection by Zika virus in French Guiana.

OBJECTIVES: To describe placental findings on prenatal ultrasound and anatomopathological examination in women with Zika virus (ZIKV) infection, and to assess their association with congenital ZIKV infection and severe adverse outcome, defined as fetal loss or congenital Zika syndrome (CZS). METHODS: This was a prospective study of pregnancies undergoing testing for maternal ZIKV infection at a center in French Guiana during the ZIKV epidemic. In ZIKV-positive women, congenital infection was defined as either a positive reverse transcription polymerase chain reaction result or identification of ZIKV-specific immunoglobulin-M in at least one placental, fetal or neonatal sample. Placental ZIKV-infection status was classified as non-exposed (placentae from non-infected women), exposed (placentae from ZIKV-infected women without congenital infection) or infected (placentae from ZIKV-infected women with proven congenital infection). Placentae were assessed by monthly prenatal ultrasound examinations, measuring placental thickness and umbilical artery Doppler parameters, and by anatomopathological examination after live birth or intrauterine death in women with ZIKV infection. The association of placental thickness during pregnancy and anatomopathological findings with the ZIKV status of the placenta was assessed. The association between placental findings and severe adverse outcome (CZS or fetal loss) in the infected group was also assessed. RESULTS: Among 291 fetuses/neonates/placentae from women with proven ZIKV infection, congenital infection was confirmed in 76 cases, of which 16 resulted in CZS and 11 resulted in fetal loss. The 215 remaining placentae from ZIKV-positive women without evidence of congenital ZIKV infection represented the exposed group. A total of 334 placentae from ZIKV-negative pregnant women represented the non-exposed control group. Placentomegaly (placental thickness > 40 mm) was observed more frequently in infected placentae (39.5%) than in exposed placentae (17.2%) or controls (7.2%), even when adjusting for gestational age at diagnosis and comorbidities (adjusted hazard ratio (aHR), 2.02 (95% CI, 1.22-3.36) and aHR, 3.23 (95% CI, 1.86-5.61), respectively), and appeared earlier in infected placentae. In the infected group, placentomegaly was observed more frequently in cases of CZS (62.5%) or fetal loss (45.5%) than in those with asymptomatic congenital infection (30.6%) (aHR, 5.43 (95% CI, 2.17-13.56) and aHR, 4.95 (95% CI, 1.65-14.83), respectively). Abnormal umbilical artery Doppler was observed more frequently in cases of congenital infection resulting in fetal loss than in those with asymptomatic congenital infection (30.0% vs 6.1%; adjusted relative risk (aRR), 4.83 (95% CI, 1.09-20.64)). Infected placentae also exhibited a higher risk for any pathological anomaly than did exposed placentae (62.8% vs 21.6%; aRR, 2.60 (95% CI, 1.40-4.83)). CONCLUSIONS: Early placentomegaly may represent the first sign of congenital infection in ZIKV-infected women, and should prompt enhanced follow-up of these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Placental infection of hepatitis B virus among Thai pregnant women: Clinical risk factors and its association with fetal infection.

OBJECTIVES: To identify the risk factors of placental and fetal infections among HBsAg-positive women. METHODS: A prospective cohort study involving HBsAg-positive pregnant women was conducted. Maternal risk factors, including serum HBeAg status, anti-HBcIgM, and HBV-DNA levels, were determined. Placental infection was identified by PCR and confirmed by DNA sequencing. Fetal infection was defined as a positive umbilical cord blood HBV-DNA at birth. RESULTS: A total of 96 HBsAg-positive women were enrolled in the study. The prevalence of placental infection was high (44 of 96; 45.8%) among HBsAg-positive women. The major risk factors for placental infection were high maternal viral load and the presence of HBeAg. Fetal infection was detected in one quarter of HBsAg-positive women (25 of 95; 25.3%). The risk of fetal infection was strongly associated with placental infection (78.3%), high maternal viral load, and the presence of HBeAg. There was no significant difference in perinatal outcomes between the groups with and without placental infection. Data on rates of chronic HBV infection in infants after fetal infection were not available. CONCLUSION: A significant association between maternal measures of viral replication and placental and fetal infection was demonstrated. These findings suggest that transplacental infection prior to birth may be a mechanism contributing to the higher rates of newborn prophylaxis failure in women with a high viral load.

Massive Perivillous Fibrin Deposition of an Enterovirus A-Infected Placenta Associated With Stillbirth: A Case Report.

Massive perivillous fibrin deposition (MFD) is a morphologically defined severe placental lesion associated with perinatal morbidity and mortality. The etiology is unknown, and recurrence risk in subsequent pregnancies is assumed to be high. In most cases, a pathologic immune reaction is supposed to be responsible for the lesion. We report a case of a pregnant woman's suffering from hand, foot, and mouth disease in the 20th gestational week. Subsequently, MFD developed in the placenta and was followed by intrauterine growth restriction and stillbirth in the 29th gestational week. Enterovirus A with high homology to Coxsackievirus A16 was detected in the placenta by means of immunohistochemisty and reverse transcription polymerase chain reaction. This infection could be a rare cause of MFD and should be taken into consideration in the differential diagnosis of the individual etiology. Recurrence risk of virus-related MFD is expected to be lower than in MFD without infectious association.

Border Disease Virus Infection of Bovine Placentas.

Subsequent to a previous study of border disease virus (BDV) horizontal transmission from a persistently BDV-infected calf to 6 seronegative pregnant heifers, the heifers were slaughtered 60 days after exposure to the infected calf, and their fetuses and placentas were examined. Immunohistochemical examination of fetal organs and placenta showed positive labeling of moderate intensity for pestivirus antigen in 3 of 6 heifers. BDV infection in these 3 animals was confirmed by the detection of BDV RNA in different organs using reverse transcription quantitative polymerase chain reaction. In the placenta, the positive cells were visualized mostly on the fetal side. In those 3 heifers that harbored an infected fetus, the placental tissue in the placentome region showed a moderate to severe mononuclear and fibrosing placentitis and, in severe cases, necrotic areas. The inflammatory population was composed predominantly of T and B cells, a substantial number of macrophages, and, to a lesser extent, plasma cells. This is a novel report of placentitis in persistently BDV-infected fetuses from pregnant heifers that became acutely infected by cohousing with a calf persistently infected with BDV, which extends previous reports on bovine viral diarrhea virus-infected and BDV-infected cattle and sheep, respectively.

Placental infectious villitis versus villitis of unknown etiology.

To assess the incidence, diagnosis, pathogenesis, and clinical and placental associations of congenital cytomegalovirus infection, 34 cases thereof diagnosed by placental/fetal or neonatal workup (group 1), and 494 placentas with villitis of unknown etiology (group 2) were extracted from a 6083-case placental database. 28 clinical and 47 placental phenotypes were compared between the two groups by Yates 2 or ANOVA using the Bonferroni correction. 26 group 1 cases did and 8 did not feature placental villitis, but all cases were positive as shown by immunohistochemistry and/or in situ hybridization. Only 5 differences were statistically significant (p Bonferroni < 0.0056): gestational age 29.8 ±6.5 vs. 35.5 ±4.9 weeks, perinatal mortality 67.6 vs. 16.2%, nonmacerated stillbirth 20.6 vs. 3.0%, macerated stillbirth 38.2 vs. 9.3%, and diffuse villous fibrosis 44.1 vs. 12.5%, between group 1 and group 2, respectively. The absence of significant differences in placental phenotypes between group 1 and group 2 other than the histological pattern of villitis indicates that not the cytomegalovirus villitis but the direct viral cytopathogenic effect on fetal organs makes the difference in the dire clinical outcome in the former. As about a third of cytomegalovirus infections show no villitis, the combination of the clinical picture and placental patterns creates the best chance to detect congenital cytomegalovirus infection.

Study of human cytomegalovirus replication in body fluids, placental infection, and miscarriage during the first trimester of pregnancy.

Intrauterine infection caused by human cytomegalovirus (HCMV) can lead to embryo, fetal, and neonatal damage. The prevalence of HCMV replication in body fluids (blood, urine, and cervicovaginal secretion) was investigated, and its effects on HCMV vertical transmission and miscarriages in early pregnant women were evaluated. HCMV DNA in body fluids was detected in 1,064 early pregnant women (624 normal pregnancies and 440 miscarriages). There were 101 cases who were HCMV DNA positive in cervicovaginal secretion and the rates were 10.9% (48/440 cases) and 8.5% (53/624 cases) in miscarriages and normal pregnancies, respectively (P > 0.05). A total of 101 cases (63 and 38 cases with and without HCMV DNA in cervicovaginal secretion, respectively) were given HCMV DNA detection in placental villi/deciduas. There were five cases (7.9%; two normal pregnancies and three miscarriages) with HCMV DNA in placental villi/deciduas among the 63 cases with HCMV DNA in cervicovaginal secretion, whereas none of the other 38 cases were detected HCMV DNA positive in their placental villi/deciduas. The percentage of HCMV DNA in placental villi/deciduas was higher in miscarriage group (9.1% [3/33]) than that in the normal pregnancy group (6.7% [2/30]), but there was no statistical significance (P > 0.05). Two cases with a higher HCMV loads in cervicovaginal secretion and placental villi/deciduas had miscarriages. These findings suggest that HCMV replication in cervicovaginal secretion can involve in placental HCMV infection, and high HCMV DNA loads in cervicovaginal secretion and placental villi/deciduas are associated with miscarriage.

Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus.

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

Association between maternal and perinatal outcomes and histological changes in the placenta of patients with Covid-19: A cohort study.

Although studies evaluated placental involvement in Covid-19 patients, few have assessed its association with clinical repercussions. The study aimed to determine the association between the clinical status and maternal and perinatal outcomes of patients with Covid-19 at delivery and changes in placental histology. It is so far the largest cohort evaluating placentas of patients infected by the SARS-CoV-2. A secondary analysis was conducted of a database from which a cohort of 226 patients, who tested real-time polymerase chain reaction-positive for Covid-19 at delivery and whose placentas were collected and submitted to pathology, was selected for inclusion. One or more types of histological changes were detected in 44.7% of the 226 placentas evaluated. The most common abnormalities were maternal vascular malperfusion (38%), evidence of inflammation/infection (9.3%), fetal vascular malperfusion (0.8%), fibrinoid changes and intervillous thrombi (0.4%). Oxygen use (P = .01) and need for admission to an intensive care unit (ICU) (P = .04) were less common in patients with placental findings, and hospital stay was shorter in these patients (P = .04). There were more fetal deaths among patients with evidence of inflammation/infection (P = .02). Fetal death, albeit uncommon, is associated with findings of inflammation/infection. Oxygen use and need for admission to an ICU were less common among patients with placental findings, probably due to the pregnancy being interrupted early. None of the other findings was associated with maternal clinical status or with adverse perinatal outcome.

Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor.

Pandemics pose a more significant threat to pregnant women than to the nonpregnant population and may have a detrimental effect on the well being of the fetus. We have developed an animal model to evaluate the consequences of a viral infection characterized by lack of fetal transmission. The experiments described in this work show that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental deficiencies. Furthermore, we demonstrate that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labor. It is critical to take into consideration the fact that during pregnancy it is not only the maternal immune system responding, but also the fetal/placental unit. Our results further support the immunological role of the placenta and the fetus affecting the global response of the mother to microbial infections. This is relevant for making decisions associated with treatment and prevention during pandemics.

Chronic histiocytic intervillositis with cytomegalovirus placentitis in a case of hydrops fetalis.

Chronic histiocytic intervillositis (CHI) is an infrequent inflammatory placental disorder associated with unfavorable pregnancy outcomes and a high rate of recurrence. This disorder is thought to reflect a maternal delayed hypersensitivity response to fetal antigen(s) in placental tissue. We report a case of a 20-week-gestation hydropic fetus in which the placenta showed chronic histiocytic intervillositis with cytomegalovirus placentitis. Immunophenotyping studies supported a delayed hypersensitivity response. This is the first report of these two diseases co-occurring, raising the possibility of a relationship between chronic histiocytic intervillositis and infection. Chronic histiocytic intervillositis may represent an idiosyncratic immune response, in this case to cytomegalovirus.

Human cytomegalovirus infection is detected frequently in stillbirths and is associated with fetal thrombotic vasculopathy.

BACKGROUND: Human cytomegalovirus (CMV) is the most common congenital infection in developed countries and is a known cause of intrauterine fetal death. We examined CMV infection in stillbirths and the relationship with histopathological findings at autopsy. METHODS: We collected liver, kidney, and placenta specimens from 130 stillbirths. CMV DNA and protein were detected using polymerase chain reaction and immunohistochemistry, along with routine autopsy of stillborn infants. RESULTS: Overall, CMV DNA was detected in 15% of singleton, >20-week stillborn infants. CMV DNA was detected in kidney (9%), liver (11%), and placenta (5%) specimens, with 75% of infections confirmed by immunohistochemistry. Fetal thrombotic vasculopathy was the only histopathological abnormality associated with CMV infection (in 60% CMV-infected vs 28% uninfected stillbirths P = .010). CONCLUSIONS: Stillbirth has multiple etiologies. However, the detection of CMV DNA in 15% of fetal tissues or placentae suggests a strong association between CMV infection in pregnancy and stillbirth. Molecular testing during postmortem investigation has an important role to determine the contribution of CMV infection.

Placental deficiency during maternal SARS-CoV-2 infection.

INTRODUCTION: Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. METHODS: This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. RESULTS: The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. DISCUSSION: The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.