Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean = 12.71%) and 3 sites greater DNAm (mean = 1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference = 3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference = 1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference = 7.86%) and females (mean absolute difference = 8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity.
Highlights
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic
Six CpGs were annotated to a Transcription Factor Binding Site (TFBS) with relatively high evidence from 4 to 6 experiments extracted from Encyclopedia of DNA Elements (ENCODE) supporting transcription binding at that region
All angiotensin-Converting Enzyme 2 (ACE2) CpGs tested differed strongly and significantly by sex with most sites showing a decrease in DNA methylation (DNAm) among females relative to males
Summary
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity.[1,2] The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. The nose is exposed to environmental challenges such as air pollution, cigarette smoke, and allergens that could modulate SARS-CoV-2 infectivity and COVID-19 severity and may explain disparities. It has been hypothesized that exposure to air pollution and cigarette smoke could worsen immune response to SARS-CoV-210,11 This is in part supported by studies demonstrating that ACE2 expression is increased after P M2.5 exposure[12,13] and among current s mokers[8,14]. CpG Name cg18458833 cg21598868 cg18877734 cg03536816 cg08559914 cg16734967 cg10408040 cg05241917 cg20119767 cg04013915 cg16716680 cg25176872 cg22422976 cg05039749 cg23232263
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