Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity

A cautionary note on altered pace of aging in the COVID-19 era

“…Patients with more severe disease course, however, exhibited a predominantly hypermethylation profile of the immunosuppressive genes [28] , [54] . This finding suggests an aberrant immune cell-based epigenetic signature of COVID-19 have been linked to immune dysfunction [23] , [27] , perturbations to the epigenetic clock, development of long COVID-19 syndrome, and all-cause mortality risk in several studies [17] , [18] , [19] , [20] . As such, COVID-19 might be a confounder in epigenetic age estimation similar to life style diversities, pathogens and pathologies that may influence the forensic interpretation of DNAm data in a previous report [53] .…”

“…Because the systematic evaluation of DNA methylation signature of COVID-19 in relation to the biological age is currently a new scientific inquiry [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , this correspondence is organized around three overarching medico-legal concerns that need to be addressed for understanding the influence of COVID-19 on forensic age estimation in survivors. These concerns include: (1) the possibilities of biological and/or epigenetic age acceleration [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , TL attrition [17] , [24] , [35] , [36] , and altered thymic function with its closely related marker (sjTrec) that may be involved in the pathogenesis of COVID-19 [30] , [31] , [32] , [33] , [34] ; (2) the presence of population differences in both vulnerability and the outcome of the infection such as mortality and long COVID syndrome which has ramifications on the precision of age estimates by the forensic models [37] , [38] , [39] , [40] , [41] ; (3) the protective effect exerted by mRNA vaccines and drugs like metformin, rapamycin, and anti-androgens as potential lifespan-extending against COVID-19 and subsequently the deceleration of epigenetic age [21] , [42] , [43] .…”

“…There is an abundance of clinical and epigenetic studies that highlighted the association between the viral life cycle of HIV [48] as well as different types of coronavirus, including SARS-CoV-2 and the molecular mechanisms linked to the host immune response to viral infections [48] , [49] , [50] , [51] , [52] , [53] . The findings of several studies showed significant differential DNA methylation pattern in brain [29] and blood samples associated in COVID-19 patients [22] , [23] , [24] , [27] , [28] , [29] . The comparative DNA methylation profiling of severe COVID-19 revealed an altered genome-wide methylome signature at 44 CpG sites denoted as the epigenetic susceptibility loci for respiratory failure cases [28] .…”

“…SARS-CoV-2, as an RNA virus, is capable of hijacking the epigenetic landscape of host immune cells to suppress the host antiviral response [22] , [30] , [49] , [50] , [51] . These epigenetic mechanisms are closely linked to the control of lymphopoiesis and the immune response depending on the disease severity [22] , [23] , [24] , [27] , [28] , [50] , [57] . Therefore, obvious cell-type shifts in the composition of blood cell have been correlated with the severity of COVID-19 disease due to the effect of COVID-19 DNAm signature.…”

“…As regards the TL, it was significantly shortened in the cases of COVID-19 in comparison to the control in three studies [24] , [35] , [36] and the long COVID compared with the COVID-free groups in a fourth study [20] . The DNAm and TL age markers were thought to be closely related as the telomere attrition leads to differentiation instability via DNA methylation [27] , [62] , [63] . However, Mongelli et al [20] and Marioni et al [63] studies suggested that both markers are regulated and work independently.…”