We are happy to report our featured article in Journal of Leukocyte Biology. There is urgency in finding effective anti-COVID-19 therapeutics if we are to alter the trajectory of the pandemic. Here, we examined genome-wide epigenetic DNA methylation (DNAm) profiles in blood from individuals with (i) severe COVID-19 disease, (ii) hospitalized influenza infection, (iii) ART naïve people with primary HIV infection, (iv) HIV+ and COVID-19 co-infection and uninfected controls to help map the DNAm landscape of severe COVID-19 that are useful for clinical assessments, pathogenic mechanism, and new therapeutic targets against SARS-CoV-2. We estimated immune cell type proportions in circulation & post mortem lungs using DNAm. We found severe COVID-19 patients to exhibit hypermethylation of antiviral defense genes IFITM1 & ISG20 with hypometylation of immune inflammation & cytokine genes NLRP3 & MX1. MX1 DNAm related with plasma levels of SARS-CoV-2 and platelet counts. Further epigenetic analysis revealed severe COVID-19 patients have an increased age acceleration phenotype and mortality risk by grimAge. Interestingly, there was no difference in telomere length compared to control. Lastly, through DNAm we identify Cystatin C and TIMP1 as a DNAm-based biomarkers in patients with COVID-19.
