Cord Blood SARS-CoV-2 IgG Antibodies and Their Association With Maternal Immunity and Neonatal Outcomes

Passive transplacental immunity is crucial for neonatal protection from infections. Data on the correlation between neonatal immunity to SARS-CoV-2 and protection from adverse outcomes is scarce. This work aimed to describe neonatal seropositivity in the context of maternal SARS-CoV-2 infection, seropositivity, and neonatal outcomes. This retrospective nested case-control study enrolled high-risk pregnant women with a SARS-CoV-2 RT-PCR positive test who gave birth at the Instituto Nacional de Perinatología in Mexico City and their term neonates. Anti-SARS-CoV-2 IgG antibodies in maternal and cord blood samples were detected using a chemiluminescent assay. In total, 63 mother-neonate dyads (mean gestational age 38.4 weeks) were included. Transplacental transfer of SARS-CoV-2 IgG occurred in 76% of neonates from seropositive mothers. A positive association between maternal IgG levels and Cycle threshold (Ct) values of RT-qPCR test for SARS-CoV-2 with neonatal IgG levels was observed. Regarding neonatal outcomes, most seropositive neonates did not require any mechanical ventilation, and none developed any respiratory morbidity (either in the COVID-19 positive or negative groups) compared to 7 seronegative neonates. Furthermore, the odds of neonatal respiratory morbidity exhibited a tendency to decrease when neonatal IgG levels increase. These results add further evidence suggesting passive IgG transfer importance.

COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes.

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.

Prevalence, clinical features, and outcomes of SARS-CoV-2 infection in pregnant women with or without mild/moderate symptoms: Results from universal screening in a tertiary care center in Mexico City, Mexico.

The perinatal consequences of SARS-CoV-2 infection are still largely unknown. This study aimed to describe the features and outcomes of pregnant women with or without SARS-CoV-2 infection after the universal screening was established in a large tertiary care center admitting only obstetric related conditions without severe COVID-19 in Mexico City. This retrospective case-control study integrates data between April 22 and May 25, 2020, during active community transmission in Mexico, with one of the highest COVID-19 test positivity percentages worldwide. Only pregnant women and neonates with a SARS-CoV-2 result by quantitative RT-PCR were included in this study. Among 240 pregnant women, the prevalence of COVID-19 was 29% (95% CI, 24% to 35%); 86% of the patients were asymptomatic (95% CI, 76%-92%), nine women presented mild symptoms, and one patient moderate disease. No pregnancy baseline features or risk factors associated with severity of infection, including maternal age > 35 years, Body Mass Index >30 kg/m2, and pre-existing diseases, differed between positive and negative women. The median gestational age at admission for both groups was 38 weeks. All women were discharged at home without complications, and no maternal death was reported. The proportion of preeclampsia was higher in positive women than negative women (18%, 95% CI, 10%-29% vs. 9%, 95% CI, 5%-14%, P<0.05). No differences were found for other perinatal outcomes. SARS-CoV-2 test result was positive for nine infants of positive mothers detected within 24h of birth. An increased number of infected neonates were admitted to the NICU, compared to negative neonates (44% vs. 22%, P<0.05) and had a longer length of hospitalization (2 [2-18] days vs. 2 [2-3] days, P<0.001); these are potential proxies for illness severity. This report highlights the importance of COVID-19 detection at delivery in pregnant women living in high transmission areas.

Clinical characteristics and risk factors for SARS-CoV-2 infection in pregnant women attending a third level reference center in Mexico City.

BACKGROUND: COVID-19 symptoms vary widely among pregnant women. We aimed to assess the most frequent symptoms amongst pregnant women with SARS-CoV-2 infection in a tertiary hospital in Mexico City. METHODS: A cross-sectional study of pregnant women attending the National Institute of Perinatology in Mexico City was performed. All women who attended the hospital, despite their symptoms, were tested for SARS-CoV-2. A multivariate-age-adjusted logistic regression was used to assess the association between the main outcome and each characteristic of the clinical history. RESULTS: A total of 1880 women were included in the data analysis. Among all women, 30.74% (n = 578) had a positive PCR for SARS-CoV-2 from which 2.7 (n = 50) were symptomatic. Symptoms associated with a positive PCR result were headache (p=.01), dyspnea (p=.043), and myalgia (p=.043). CONCLUSIONS: At universal screening for SARS-CoV-2, one-third of the population had a positive result, while those symptoms associated with a positive PCR were headache, dyspnea, and myalgia.

Fetal and placental infection with SARS-CoV-2 in early pregnancy.

To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second- and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse transcription quantitative real-time polymerase chain reaction, immunofluorescence, and electron microscopy methods. SARS-CoV-2 nucleocapsid protein, viral RNA, and particles consistent with coronavirus were found in the placenta and fetal tissues, accompanied by RNA replication revealed by double-stranded RNA (dsRNA) positive immunostain. Prominent damage of the placenta and fetal organs were associated with a hyperinflammatory process identified by histological examination and immunohistochemistry. The findings provided in this study document that congenital SARS-CoV-2 infection is possible during the first trimester of pregnancy and that fetal organs, such as lung and kidney, are targets for coronavirus. The infection and multi-organic fetal inflammation produced by SARS-CoV-2 during early pregnancy should alert clinicians in the assessment and management of pregnant women for possible fetal consequences and adverse perinatal outcomes.

Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19.

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.