SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

Abstract

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.

1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit

“…Because its level creases sharply in the plasma of COVID-19 patients, it was proposed as a potential me olomic biomarker [85,86]. XYLB was also identified among the top hypermethylated ge [87]. XYLB (xylulokinase) catalyzes the ATP-dependent phosphorylation of D-xylulose to produce xylulose 5-phosphate (Xu5P), which is a key regulator of glucose metabolism and lipogenesis [83].…”

“…Because its level decreases sharply in the plasma of COVID-19 patients, it was proposed as a potential metabolomic biomarker [85,86]. XYLB was also identified among the top hypermethylated genes [87].…”

“…The level of the XYLB product Xu5P decreased sharply in the plasma during SARS-CoV-2 infection [85,86], while XYLB was also identified as one of the top hypermethylated genes [87]. Human coronaviruses can activate and hijack the proteostasis guardian HSF1 to enhance viral replication [91].…”

Maternal and neonatal COVID-19 – the pandemic experience in a tertiary maternity unit in Romania – unicentric, prospective study

“…Increased morbidity and mortality in pregnant women and newborns is recognized for many years with viral infections during pregnancy, therefore, even at the beginning of the pandemic both pregnant women and newborns were considered at high risk for SARS-CoV-2 infection and its complications. Soon after pandemic onset, reports coming first from China and thereafter from all over the world described adverse outcomes of COVID-19 during pregnancy: increased rates of prematurity, stillbirth, fetal death, intrauterine growth restriction (IUGR), fetal distress, maternal respiratory failure (with increased need for oxygen, respiratory support, and intensive care unit admission), preeclampsia, C-section delivery, and maternal and neonatal death as compared to non-exposed pregnancies [16][17][18][19][20][21][22][23][24]. Studies also reported an even more complicated course of COVID-19 in pregnancies complicated with lung, cardiovascular, renal, and liver conditions, high blood pressure, diabetes, obesity, anti-phospholipidic syndrome, and thrombophilia [9,25].…”