Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors

Abstract

The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).

Epigenetic Clocks Are Not Accelerated in COVID-19 Patients

“…In fact, it has been demonstrated that HIV infection leads to an average aging advancement of 4.9 years [18]. It has also been suggested that such off-set occurs also if the infection with SARS-CoV-2 has been persistent for a longer time in COVID-19 survivors, particularly in a cohort younger than 60 years [19]. However, blood samples that were taken before a fatal COVID-19 infection were not available, and it appears unlikely that the COVID-19 infection rejuvenates a previously accelerated epigenetic age;…”

Longitudinal study of DNA methylation and epigenetic clocks prior to and following test-confirmed COVID-19 and mRNA vaccination

“…Moreover, prior multi-omic analysis has shown that the Levine clock accelerates with cellular senescence and mitochondrial dysfunction (Liu et al, 2020). Prior studies of epigenetic clocks in COVID-19 utilized different sets of clocks which may explain their conflicting results (Corley et al, 2021; Franzen et al, 2021; Mongelli et al, 2021a). Interrogating a wide array of clocks simultaneously is essential for determining which clocks are most related to COVID-19 or vaccination.…”

“…Moreover, epigenetic clocks are accurate predictors of mortality risk (Lu et al, 2019), biomarkers of pathogen exposure (Horvath and Levine, 2015; Boulias et al, 2016; Corley et al, 2021), and correlates of lung function and immune inflammation (Hillary et al, 2020, 2021). Evidence suggests that severe COVID-19 disease may impact certain epigenetic clocks (Corley et al, 2021; Mongelli et al, 2021a) and biological aging captured by PhenoAge may inform COVID-19 outcomes (Kuo et al, 2020). More recent epigenetic clock studies have reported conflicting evidence for biological age acceleration and telomere shortening in COVID-19 survivors (Mongelli et al, 2021b), with some finding no clock acceleration in COVID-19 patients (Franzen et al, 2021).…”

PTSD as an Endothelial Disease: Insights From COVID-19

“…Moreover, psychological stress-upregulated ROS trigger telomere attrition, a phenomenon encountered in both PTSD and severe COVID-19, linking these conditions to premature aging (Atanackovic et al, 2002;Yegorov et al, 2020). Interestingly, it was reported that aside from AT-1Rs and ET-1Rs, mitochondria also expressed gamma-aminobutyric acid (GABA), glucocorticoid, and monoamine oxidase A and B receptors, further connecting the organelle to SRDs (Krueger, 1995;Mongelli et al, 2021).…”