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
João Malato,
Franziska Sotzny,
Sandra Bauer,
Helma Freitag,
André Fonseca,
Anna D. Grabowska,
Luís Graça,
Clara Cordeiro,
Luís Nacul,
Eliana M. Lacerda,
Jesus Castro-Marrero,
Carmen Scheibenbogen,
Francisco Westermeier,
Nuno Sepúlveda
Affiliations
João Malato
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; CEAUL – Centro de Estatística e Aplicações, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal
Franziska Sotzny
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Germany; Corresponding author.
Sandra Bauer
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Germany
Helma Freitag
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Germany
André Fonseca
Faculdade de Ciências e Tecnologia, Universidade do Algarve, Faro, Portugal
Anna D. Grabowska
Department of Biophysics, Physiology, and Pathophysiology, Medical University of Warsaw, Warsaw, Poland
Luís Graça
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
Clara Cordeiro
CEAUL – Centro de Estatística e Aplicações, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; Faculdade de Ciências e Tecnologia, Universidade do Algarve, Faro, Portugal
Luís Nacul
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Complex Chronic Diseases Program, British Columbia Women's Hospital and Health Centre, Vancouver, British Columbia, Canada
Eliana M. Lacerda
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
Jesus Castro-Marrero
Vall d’Hebron Hospital Research Institute, Division of Rheumatology, ME/CFS Unit, Universitat Autònoma de Barcelona, Barcelona, Spain
Carmen Scheibenbogen
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Germany
Francisco Westermeier
Institute of Biomedical Science, Department of Health Studies, FH Joanneum University of Applied Sciences, Graz, Austria; Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O´Higgins, Santiago, Chile
Nuno Sepúlveda
CEAUL – Centro de Estatística e Aplicações, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Germany; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Corresponding author.
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.
