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Preprint in English | Other preprints | ID: ppcovidwho-295386


Patients affected by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) show specific epigenetic and gene expression signatures of the disease. However, it is unknown whether these signatures include abnormal levels of the human angiotensin-converting enzymes, ACE and ACE2, the latter being the main receptor described for the host-cell invasion by SARS-CoV-2. To investigate that, we first re-analyzed available case-control epigenome-wide association studies based on DNA methylation data, and case-control gene expression studies based on microarray data. From these published studies, we found an association between ME/CFS and 4 potentially hypomethylated probes located in the ACE locus. We also found another disease association with one hypomethylated probe located in the transcription start site of ACE2. The same disease associations were obtained for women but not for men after performing sex-specific analyses. In contrast, a meta-analysis of gene expression levels could not provide evidence for a differentially expression of ACE and ACE2 in affected patients when compared to healthy controls. In line with this negative finding, the analysis of a new data set on the gene expression of ACE and ACE2 in peripheral blood mononuclear cells did not find any differences between a female cohort of 37 patients and 34 age-matched healthy controls. Future studies should be conducted to extend this investigation to other potential receptors used by SARS-CoV-2. These studies will help researchers and clinicians to improve the understanding of the health risk imposed by this virus when infecting patients affected by this debilitating disease.

Heliyon ; 7(8): e07665, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1330844


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.

Neurology ; 95(10): 445-449, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-999777


Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

Brain/diagnostic imaging , Coronavirus Infections/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/cerebrospinal fluid , Pneumonia, Viral/cerebrospinal fluid , RNA, Viral/cerebrospinal fluid , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interleukin-6/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/diagnostic imaging , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Leukoencephalitis, Acute Hemorrhagic/therapy , Magnetic Resonance Imaging , Middle Aged , Neurofilament Proteins/cerebrospinal fluid , Pandemics , Plasma Exchange , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , Viral Tropism , tau Proteins/cerebrospinal fluid