The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data

Abstract

People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report a high frequency of viral infections and flu-like symptoms during their disease course. Given that this reporting agrees with different immunological  abnormalities and altered gene expression profiles observed in the disease, we aimed at answering whether the expression of the human angiotensin-converting  enzyme 2 (ACE2), the major cell entry receptor for SARS-CoV-2, is also altered in  these patients. In particular, a low expression of ACE2 could be indicative of a  high risk of developing COVID-19. We then performed a meta-analysis of public  data on CpG DNA methylation and gene expression of this enzyme and its homologous ACE protein in peripheral blood mononuclear cells and related subsets. We found  that patients with ME/CFS have decreased methylation levels of four CpG probes in  the ACE locus (cg09920557, cg19802564, cg21094739, and cg10468385) and of another  probe in the promoter region of the ACE2 gene (cg08559914). We also found a  decreased expression of ACE2 but not of ACE in patients when compared to healthy  controls. Accordingly, in newly collected data, there was evidence for a  significant higher proportion of samples with an ACE2 expression below the limit  of detection in patients than healthy controls. Altogether, patients with ME/CFS  can be at a higher COVID-19 risk and, if so, they should be considered a priority  group for vaccination by public health authorities. To further support this  conclusion, similar research is recommended for other human cell entry receptors  and cell types, namely, those cells targeted by the virus.