DataSheet_1_Impact of COVID-19 during pregnancy on placental pathology, maternal and neonatal outcome – A cross-sectional study on anemic term pregnant women from a tertiary care hospital in southern India.docx

BackgroundSARS-CoV-2 infection during pregnancy may cause adverse maternal, neonatal and placental outcomes. While tissue hypoxia is often reported in COVID-19 patients, pregnant women with anemia are suspected to be more prone to placental hypoxia-related injuries.MethodsThis hospital-based cross-sectional study was conducted between August-November 2021, during COVID-19 second wave in India. Term pregnant women (N=212) admitted to hospital for delivery were enrolled consecutively. Since hospital admission mandated negative RT-PCR test for SARS-CoV-2 virus, none had active infection. Data on socio-demography, COVID-19 history, maternal, obstetric, and neonatal outcomes were recorded. Pre-delivery maternal and post-delivery cord blood samples were tested for hematological parameters and SARS-CoV-2 IgG. Placentae were studied for histology.ResultsOf 212 women, 122 (58%) were seropositive for SARS-CoV-2 IgG, but none reported COVID-19 history; 134 (63.2%) were anemic. In seropositive women, hemoglobin (p=0.04), total WBC (p=0.009), lymphocytes (p=0.005) and neutrophils (p=0.02) were significantly higher, while ferritin was high, but not significant and neutrophils to lymphocytes (p=0.12) and platelets to lymphocytes ratios (p=0.03) were lower. Neonatal outcomes were similar. All RBC parameters and serum ferritin were significantly lower in anemic mothers but not in cord blood, except RDW that was significantly higher in both, maternal (p=0.007) and cord (p=0.008) blood from seropositive anemic group compared to other groups. Placental histology showed significant increase in villous hypervascularity (p=0.000), dilated villous capillaries (p=0.000), and syncytiotrophoblasts (p=0.02) in seropositive group, typically suggesting placental hypoxia. Maternal anemia was not associated with any histological parameters. Univariate and multivariate logistic regression analyses of placental histopathological adverse outcomes showed strong association with SARS-CoV-2 seropositivity but not with maternal anemia. When adjusted for several covariates, including anemia, SARS-CoV-2 seropositivity emerged as independent risk factor for severe chorangiosis (AOR 8.74, 95% CI 3.51-21.76, pConclusionAsymptomatic COVID-19 during pregnancy seemed to be associated with various abnormal placental histopathologic changes related to placental hypoxia independent of maternal anemia status. Our data supports an independent role of SARS-CoV-2 in causing placental hypoxia in pregnant women.</p

Mitochondrial and ER-Targeted eCALWY Probes Reveal High Levels of Free Zn²⁺

Zinc (Zn²⁺) ions are increasingly recognized as playing an important role in cellular physiology. Whereas the free Zn²⁺ concentration in the cytosol has been established to be 0.1–1 nM, the free Zn²⁺ concentration in subcellular organelles is not well-established. Here, we extend the eCALWY family of genetically encoded Förster Resonance Energy Transfer (FRET) Zn²⁺ probes to permit measurements in the endo­(sarco)­plasmic reticulum (ER) and mitochondrial matrix. Deployed in a variety of mammalian cell types, these probes reveal resting mitochondrial free [Zn²⁺] values of ∼300 pM, somewhat lower than in the cytosol but 3 orders of magnitude higher than recently reported using an alternative FRET-based sensor. By contrast, free ER [Zn²⁺] was found to be ≥5 nM, which is >5000-fold higher than recently reported but consistent with the proposed role of the ER as a mobilizable Zn²⁺ store. Treatment of β-cells or cardiomyocytes with sarco­(endo)­plasmic reticulum Ca²⁺-ATPase inhibitors, mobilization of ER Ca²⁺ after purinergic stimulation with ATP, or manipulation of ER redox, exerted no detectable effects on [Zn²⁺]_ER. These findings question the previously proposed role of Ca²⁺ in Zn²⁺ mobilization from the ER and suggest that high ER Zn²⁺ levels may be an important aspect of cellular homeostasis