Maternal SARS-CoV-2 exposure alters infant DNA methylation

Hill, Robert A.; Gibbons, Andrew S.; Han, Uni; Suwakulsiri, Wittaya; Taseska, Angela; Hammet, Fleur; Southey, Melissa C.; Malhotra, Atul; Fahey, Michael; Palmer, Kirsten R.; Hunt, Rod W; Lim, Izaak; Newman-Morris, Vesna; Sundram, Suresh

doi:10.1016/j.bbih.2022.100572

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…DNA extraction and bisulphite conversion were performed as previously described 24 . Methylation pro ling was conducted using In nium Methylation EPIC BeadChip (Illumina, San Diego, CA) and imaged using Illumina iScan System.…”

Section: Dna Extraction Bisulphite Conversion and Dna Methylation Ana...mentioning

confidence: 99%

“…Methylation analysis was carried out as previously described 24 and following the R package "ChAMP", which includes a pre-processing pipeline of quality checks (using min R package) 25 , normalisation (using Beta MIxture Quantile dilation (BMIQ) method 26 and batch effect corrections (using sva R package) 27,28 . R package "limma" 29,30 was used to identify differentially methylated CpG sites in SARS-…”

Section: Dna Methylation Analysismentioning

confidence: 99%

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Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment

Hill,

Gibbons,

Suwakulsiri

et al. 2024

Preprint

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Maternal infections during pregnancy can increase the risk to offspring of developing a neurodevelopmental disorder. Given the global prevalence and severity of infection with Severe Acute Respiratory Syndrome related Coronavirus 2 (SARS-CoV-2), the objective of this study was to determine if in utero exposure to severe maternal SARS-CoV-2 infection alters infant neurodevelopmental outcomes at 12 months and to identify potential biological markers of adverse infant outcomes. Mother-infant dyads exposed to severe SARS-CoV-2 infection (requiring hospitalization) during pregnancy and age and sociodemographic matched control dyads were recruited from Monash Medical Centre, Australia in 2021/22 and prospectively assessed over 12 months. Maternal serum cytokine levels and Edinburgh Postnatal Depression Scale (EPDS) scores were assessed at birth. DNA methylation was assessed from infant buccal swabs at birth (Illumina EPIC BeadChip). Infant neurodevelopmental outcomes at 12 months were assessed using the Ages and Stages Questionnaire (ASQ-3). Mothers exposed to severe SARS-CoV-2 exhibited elevated serum IL-6 and IL-17A and higher EPDS scores than controls at birth. Infants exposed to severe SARS-CoV-2 in utero demonstrated over 3000 significant differentially methylated sites within their genomes compared to non-exposed (adjusted p-value < 0.05), including genes highly relevant to ASD and synaptic pathways. At 12 months, severe SARS-CoV-2 exposed infants scored lower on the ASQ-3 than non-exposed infants and communication and problem-solving scores negatively correlated with maternal Il-6 levels at birth. DNA methylation changes therefore unveil potential mechanisms linking infection exposure to delayed neurodevelopment and maternal serum IL-6 levels may be a potential biomarker of child developmental delay.

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Section: Dna Extraction Bisulphite Conversion and Dna Methylation Ana...mentioning

confidence: 99%

Section: Dna Methylation Analysismentioning

confidence: 99%

Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment

Hill,

Gibbons,

Suwakulsiri

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…More recently, Hill et.al, reported differential methylation of several genes including genes in pathways that play a role in human neurodevelopment in buccal swabs on infants exposed to in utero COVID-19 infection. 62 The altered methylation pattern identified in genes related to hepatic, renal, and cardiac diseases show a potential connection to long-term consequences of COVID-19 infection. Our study, however, also has several limitations, for example, the sample size of 16 neonates is small, but similar limited sample sizes have been used in studies investigating differential DNA methylation patterns.…”

Section: Strn4 (Striatin 4) Is Associated With Muscularmentioning

confidence: 99%

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

et al. 2023

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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.

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“…69 The preliminary findings from that study revealed that the offspring of mothers exposed to SARS-CoV-2 had a differentially altered methylation of genes in regions correlated to neurodevelopment. 70…”

Section: Epigenetic Mechanisms and Sars-cov-2 Infectionmentioning

confidence: 99%

Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

Khouri,

de Souza Candido,

Poli-Frederico

et al. 2023

Gene Expr

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Host-specific genetics, such as epigenetic profiles and genetic variants, can contribute to the pathogenesis of infectious diseases. Strong associations have been previously identified in infections by human immunodeficiency virus (HIV), Plasmodium falciparum, norovirus, and influenza A virus. Despite the efforts to characterize the role of host genetics in severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2) infection, this comprehension remains incipient. Coronavirus disease 2019 (COVID-19) can evolve with a wide spectrum of manifestations, ranging from asymptomatic and mild cases to severe forms with acute respiratory distress syndrome, multi-organ complications, and even death. Classic clinical risk factors only partially explain this interindividual variability, suggesting that host genetics may contribute to the heterogeneity of courses. Robust evidence has revealed the multiple associations of genes (ABO,

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Maternal SARS-CoV-2 exposure alters infant DNA methylation

Cited by 7 publications

References 46 publications

Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment

Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment

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

Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

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