SARS-CoV-2-induced hypomethylation of the ferritin heavy chain (FTH1) gene underlies serum hyperferritinemia in severe COVID-19 patients.

High serum ferritin (hyperferritinemia), a reliable hallmark of severe COVID-19 often associates with a moderate decrease in serum iron (hypoferremia) and a moderate increase in serum hepcidin. This suggests that hyperferritinemia in severe COVID-19 is reflective of inflammation rather than iron overload. To test this possibility, the expression status of ferritin heavy chain (FTH1), transferrin receptor 1 (TFRC), hepcidin (HAMP), and ferroportin (SLC40A1) genes and promoter methylation status of FTH1 and TFRC genes were examined in blood samples obtained from COVID-19 patients showing no, mild or severe symptoms and in healthy-donor monocytes stimulated with SARS-CoV-2-derived peptides. Severe COVID-19 samples showed a significant increase in FTH1 expression and hypomethylation relative to mild or asymptomatic COVID-19 samples. S-peptide treated monocytes also showed a significant increase in FTH1 expression and hypomethylation relative to that in controls; treatment with ECD or NP did not change FTH1 expression nor its methylation status. In silico and in vitro analysis showed a significant increase in the expression of the TET3 demethylase in S peptide-treated monocytes. Findings presented here suggest that S peptide-driven hypomethylation of the FTH1 gene promoter underlies hyperferritinemia in severe COVID-19 disease.

COVID-19 and alcohol use disorder: putative differential gene expression patterns that might be associated with neurological complications.

BACKGROUND: Several lines of evidence suggest that SARS-CoV-2 invasion of the central nervous system leads to meningitis and encephalopathy syndromes. Additionally, chronic alcoholics were found to be at a higher risk of developing mental health problems and serious neurological manifestations, if exposed to SARS-CoV-2 infection. METHODS: Herein, we studied RNA seq data from alcoholics' brain tissue and COVID-19 patient's brain tissue to identify the common differentially expressed genes. RESULTS: Overlap analysis depicted the expression of seven genes (GHRL, SLN, VGF, IL1RL1, NPTX2, PDYN, and RPRML) that were significantly upregulated in both groups. Along with these, protein-protein interaction analysis revealed 10 other key molecules with strong interactions with the aforementioned genes. CONCLUSIONS: Taken together with the functional effect of these genes, we suggest a strong molecular link between COVID-19-induced severities and neurological impairment in patients suffering from alcohol abuse disorder. These findings emphasize the importance of identifying chronic alcoholism as a risk factor for developing cognitive and memory impairment in COVID-19 patients.

SARS-CoV-2: Can sunlight exposure reduce the risk of developing severe consequences of COVID-19?

Herein it is proposed that sufficient exposure to sunlight (UVB) modulates host gene expression, offering protection against severe consequences of COVID-19. This could be in addition to sunlight (UVB)-mediated protection by directly inactivating the virus and limiting the viral load. It is suggested that inhibition of CCR2, DPP9, HSPA1L, IFNAR2, OAS1, and TYK2 may, in part, explain UVB-mediated protection against severe consequences of COVID-19.

COVID-19: Is There a Link between Alcohol Abuse and SARS-CoV-2-Induced Severe Neurological Manifestations?

For the first time, it is shown that severe COVID-19 associated genes (CCR2, DPP9, HSPA1L, TYK2, OAS1, ACE2, and TMPRSS2) were also upregulated in the brain tissue of chronic alcoholics. It is proposed that chronic alcohol abuse should be considered as an important factor in COVID-19-associated neurological complications.

COVID-19: Does SARS-CoV-2 Modulate Acanthamoeba Epigenetics to Enhance Survival and Transmission in the Environment?

For the first time, we propose the role of epigenetic mechanisms in severe acute respiratory syndrome coronavirus-2 survival inside Acanthamoeba and possible transmission via airborne cysts.

SARS-CoV-2 Infection-Induced Promoter Hypomethylation as an Epigenetic Modulator of Heat Shock Protein A1L (HSPA1L) Gene.

Numerous researches have focused on the genetic variations affecting SARS-CoV-2 infection, whereas the epigenetic effects are inadequately described. In this report, for the first time, we have identified potential candidate genes that might be regulated via SARS-CoV-2 induced DNA methylation changes in COVID-19 infection. At first, in silico transcriptomic data of COVID-19 lung autopsies were used to identify the top differentially expressed genes containing CpG Islands in their promoter region. Similar gene regulations were also observed in an in vitro model of SARS-CoV-2 infected lung epithelial cells (NHBE and A549). SARS-CoV-2 infection significantly decreased the levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in lung epithelial cells. Out of 14 candidate genes identified, the expression of 12 genes was upregulated suggesting promoter hypomethylation, while only two genes were downregulated suggesting promoter hypermethylation in COVID-19. Among those 12 upregulated genes, only HSPA1L and ULBP2 were found to be upregulated in AZA-treated lung epithelial cells and immune cells, suggesting their epigenetic regulation. To confirm the hypomethylation of these two genes during SARS-CoV-2 infection, their promoter methylation and mRNA expression levels were determined in the genomic DNA/RNA obtained from whole blood samples of asymptomatic, severe COVID-19 patients and equally matched healthy controls. The methylation level of HSPA1L was significantly decreased and the mRNA expression was increased in both asymptomatic and severe COVID-19 blood samples suggesting its epigenetic regulation by SARS-CoV-2 infection. Functionally, HSPA1L is known to facilitate host viral replication and has been proposed as a potential target for antiviral prophylaxis and treatment.