RESUMO
Background: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 18.4% of total Covid-19 cases were reported in children. Even though vertical transmission from mother to infant is likely to occur at a low rate, exposure to COVID-19 during fetal life may alter DNA methylation patterns with potential long-term effects. Objective: To determine if COVID-19 infection during pregnancy alters the DNA methylation patterns in umbilical cord blood cells from term infants and to identify potential pathways and genes affected by exposure to COVID-19 infection. Methods: Umbilical cord blood was collected from 8 infants exposed to COVID-19 during pregnancy and 8 control infants with no COVID-19 exposure. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC Array. Results: 119 differentially methylated loci were identified at the FDR level of 0.20 (64 hypermethylated loci and 55 hypomethylated loci) in umbilical cord blood cells of COVID-19 exposed neonates compared to the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to stress response (corticotropin releasing hormone signaling, glucocorticoid receptor signaling, and oxytocin in brain signaling pathway), and cardiovascular disease and development (nitric oxide signaling in the cardiovascular system, apelin cardiomyocyte signaling pathways, factors promoting cardiogenesis, and renin-angiotensin signaling). The genes affected by the differential methylations were associated with cardiac, renal, hepatic, neurological diseases, developmental and immunological disorders. Conclusions: COVID-19 induces differential DNA methylation in umbilical cord blood cells. The differentially methylated genes may contribute to hepatic, renal, cardiac, developmental and immunological disorders in offspring born to mothers with COVID-19 infection during pregnancy, and their developmental regulation.
RESUMO
Decidual vasculopathy (DV) is a general term for a number of lesions involving uteroplacental vessels. It is often seen in preeclamptic placentas and indicates a disorder of uteroplacental malperfusion and is associated with placental ischemia and infarction. Although some have advocated submitting special sections in order to better document DV, it is unclear which placental sections have the highest yield in demonstrating these abnormal vessels. Seventy-six consecutive cases of decidual vasculopathy were identified and evaluated for location of DV, as well as presence of other lesions of ischemic change, infarcts, and retroplacental hematomas. Sections reviewed were the membrane roll (MR), full thickness (FT) sections of the placental disc, and sections specifically of the basal plate (BP). DV was found in the MR in 67.1% of cases, in FT sections in 32.9%, and in the BP in 25.0% of cases ( P value = .004). DV was exclusive to the MR in 53.9%, the FT in 14.5%, and the BP in 9.2%. DV was present in 2 locations in 19.7% and in all 3 locations in 2.6%. The presence of DV in any location (MR, FT, and BP) was associated with placental ischemic change but not specifically with infarcts or retroplacental hematomas. The specific location of DV showed no difference in the presence of placental lesions. Our findings indicate DV is often present in 1 location and is associated with lesions of malperfusion. It is recommended that when clinically indicated, additional sections are submitted to demonstrate decidual vasculopathy.
