Epigenetic Consequences: The Impact of COVID-19 Exposure During Pregnancy on Neonatal DNA Methylation


The COVID-19 pandemic has had a devastating impact worldwide, with the United States experiencing over 1 million deaths attributed to the disease. The highly infectious nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has contributed to its rapid spread and severe outcomes.

While efforts to control the virus through vaccination have been successful, it is expected that SARS-CoV-2 will remain present and become endemic.

The impact of COVID-19 on the pediatric population, including neonates, has been a cause for concern, as complications such as multisystem inflammatory syndrome in children (MIS-C) have been well-documented. Neonates, in particular, are a vulnerable subgroup that requires a deeper understanding of the effects of COVID-19.

Effects of COVID-19 on the Perinatal Environment

Although vertical transmission of SARS-CoV-2 from mother to infant is relatively low, active disease in neonates can still be severe. Studies have shown that mothers with COVID-19 are more likely to experience fetal distress, preterm birth, and lower birth weight compared to controls.

Adverse perinatal outcomes from maternal COVID-19 exposure are thought to be related to placental pathological thrombotic, vascular, and inflammatory changes. These changes can lead to a fetal inflammatory response, immune dysregulation, and epigenetic alterations that may have long-term consequences in offspring.

Epigenetic Mechanisms and DNA Methylation

The perinatal environment has been shown to influence epigenetic changes that can impact disease outcomes. One such mechanism is DNA methylation, which involves the addition of a methyl group to cytosine residues in specific sites, leading to transcriptional regulation. Intrauterine infections have been associated with DNA methylation changes in neonatal genes.

Similarly, exposure to COVID-19 during pregnancy is likely to have a similar effect on fetal DNA methylation. Understanding early epigenetic signatures of COVID-19 exposure during pregnancy can help identify at-risk offspring who may benefit from close monitoring and follow-up.

DNA Methylation Patterns in Neonates Exposed to COVID-19

In an observational study, researchers evaluated the DNA methylation patterns of umbilical cord blood (UCB) cells from neonates exposed to COVID-19 in utero. They compared these patterns with controls to better understand the epigenetic mechanisms associated with exposure to the virus during pregnancy and their developmental regulation.

The study found that COVID-19 infection during pregnancy was associated with differential DNA methylation in UCB cells. The affected genes were related to stress response, cardiovascular disease and development, and various diseases and disorders. The differential methylation patterns observed in these genes could potentially have short- and long-term impacts on offspring health.

Hypermethylated and Hypomethylated Genes

The study identified several hypermethylated and hypomethylated genes in neonates exposed to COVID-19. Hypermethylated genes included XYLB, CLDN6, UBTF, LPCAT2, STRN4, and HLA-DPB1. These genes are involved in glucose metabolism, tight junction-specific obliteration of intercellular space, neurodegeneration, and other diseases. Hypomethylated genes included BMP7, RHOBTB1, WWOX, and HLA-DOB. These genes are associated with bone disorders, tumor suppression, Alzheimer’s disease, and other conditions.

Implications for Offspring Health

The differential methylation patterns observed in genes related to stress response, cardiovascular development, and disease suggest that exposure to COVID-19 during pregnancy can potentially affect child development and increase the risk of behavior and psychological disorders. Additionally, altered immune function and increased susceptibility to infections may be possible consequences of the observed DNA methylation changes. These epigenetic alterations have the potential to influence gene expression and cellular functioning throughout the individual’s lifespan.

It is important to note that the long-term health implications of these DNA methylation changes in neonates exposed to COVID-19 during pregnancy are still not fully understood. Further research is needed to investigate the specific functional consequences of these epigenetic modifications and their association with various diseases and disorders.

Early detection and monitoring of these epigenetic changes may enable healthcare providers to identify individuals at higher risk for certain health conditions and implement appropriate interventions and preventive measures. This could include personalized healthcare plans, targeted screenings, and early interventions to mitigate potential adverse health outcomes associated with COVID-19 exposure during pregnancy.

Additionally, understanding the epigenetic effects of COVID-19 exposure during pregnancy can contribute to our knowledge of the long-term consequences of viral infections on the developing fetus. This information can inform public health strategies and guidelines to protect pregnant individuals and their offspring during future outbreaks of viral infections.


Exposure to COVID-19 during pregnancy has been associated with adverse perinatal outcomes, and emerging evidence suggests that it can also lead to epigenetic changes in neonates, specifically DNA methylation alterations. These changes may affect genes involved in stress response, cardiovascular development, immune function, and various diseases and disorders. Understanding the epigenetic consequences of COVID-19 exposure during pregnancy is crucial for identifying potential long-term health risks in offspring and developing appropriate strategies for monitoring and intervention. Further research is needed to elucidate the functional implications of these epigenetic modifications and their association with specific health outcomes.

reference link : https://journals.sagepub.com/doi/full/10.1177/25168657231184665


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