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. — CFSMEATLAS
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.
Malato, João, Sotzny, Franziska, Bauer, Sandra et al. · Heliyon · 2021 · DOI
Quick Summary
This study looked at whether people with ME/CFS have lower levels of a protein called ACE2, which the COVID-19 virus uses to enter cells. The researchers analyzed existing genetic data from ME/CFS patients and found that ACE2 levels were indeed reduced in ME/CFS patients compared to healthy people. The authors suggest this may put ME/CFS patients at higher risk for severe COVID-19 and recommend they be prioritized for vaccination.
Why It Matters
ME/CFS patients report frequent viral infections and atypical immune responses, making understanding their COVID-19 vulnerability clinically important. If ME/CFS patients indeed have reduced ACE2 expression conferring higher COVID-19 risk, this evidence could inform public health vaccination priorities and clinical management strategies for this vulnerable population.
Observed Findings
Decreased methylation at four CpG probes in the ACE locus in ME/CFS patients compared to healthy controls
Decreased methylation at one CpG probe (cg08559914) in the ACE2 promoter region in ME/CFS patients
Significantly reduced ACE2 gene expression in ME/CFS patients versus healthy controls
Higher proportion of ME/CFS samples with ACE2 expression below the limit of detection compared to healthy controls
No significant difference in ACE gene expression between ME/CFS patients and healthy controls
Inferred Conclusions
ME/CFS patients may have elevated risk for severe COVID-19 due to reduced ACE2 expression
ME/CFS patients should be considered a priority population for COVID-19 vaccination by public health authorities
Altered DNA methylation patterns in ACE and ACE2 loci may contribute to the immunological abnormalities observed in ME/CFS
The reduced ACE2 expression pattern in ME/CFS is consistent with other reported immune dysfunction in the disease
Remaining Questions
Is reduced ACE2 expression present in respiratory tissues (lungs and airways) where COVID-19 primarily infects, or only in peripheral blood?
What This Study Does Not Prove
This study does not prove that low ACE2 expression causes ME/CFS or that it directly causes worse COVID-19 outcomes in ME/CFS patients—only that the association exists. The analysis is restricted to peripheral blood cells and may not reflect ACE2 levels in respiratory tissues where COVID-19 infection primarily occurs. The study is observational and cannot establish whether reduced ACE2 is a cause or consequence of ME/CFS pathology.