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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.
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1 University of California, Berkeley, Division of Environmental Health Sciences, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878); University of California, Berkeley, Center for Computational Biology, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
2 Harvard Medical School and Harvard Pilgrim Health Care Institute, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
3 Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
4 Columbia University, Department of Environmental Health Sciences, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729)
5 Harvard Medical School and Harvard Pilgrim Health Care Institute, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts General Hospital, Diabetes Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)
6 Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Department of Environmental Health, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)