Evidence for Biological Age Acceleration and Telomere Shortening in Covid19 Survivors

Abstract

Introduction & Backgroundthe SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokines release, and immunodepression. 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 post-COVID19 syndrome (PPCS) is a common finding. In patients who survived the SARS-CoV-2 infection, overt PPCS presents one or more symptoms such as fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. The pathophysiology of PPCS is currently poorly understood, and whether epigenetic mechanisms are involved in this process is unexplored.Methods & ResultsIn this study, a cohort of 117 COVID19 survivors (post-COVID19) and 144 non-infected volunteers (COVID19-free) were analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. Besides, telomere length (TL) and ACE2 and DPP4 receptor expression were determined. The results show a consistent biological age increase in the post-covid population (58,44 ± 14,66 ChronoAge Vs. 67,18 ± 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 ± 7,29 years (+5.25 years above range of normality) compared to 3,68 ± 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 ± 2,39 Kb vs. COVID19-free: 10,67 ± 11,69 Kb; P<0,0001). Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change.ConclusionIn light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID19 condition, particularly in the younger (<60 years). Although the consequences of such modifications on the long-term clinical outcome remain unclear, they might indicate a direction to investigate the pathophysiological basis of the post-COVID19 syndrome.

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

“…Previous studies including our work reported epigenetic age perturbations associated with severe hospitalized COVID-19 in older individuals (Corley et al, 2021; Mongelli et al, 2021b). We sought to investigate in this pre- and post-COVID-19 cohort of non-hospitalized COVID-19 and relatively healthy individuals whether COVID-19 exposure impacted epigenetic clock estimates.…”

“…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). Whether changes occur to epigenetic clocks in healthy individuals that recover from non-hospitalized COVID-19 remains unclear.…”

COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis

“…Patients with IPF have shortened telomeres; short telomeres and TERT/TERC-disease associated variants were associated with specific clinical and biological features and reduced transplant-free survival (109, 110). Similarly, short telomeres increase the risk of severe COVID-19(86, 111, 112), pulmonary fibrosis and poorer outcomes(112, 113). It is possible that injury, DNA damage and IL15 signalling in AT2 cells are one component in the profibrogenic cascade and suggest that IL15-targeted therapeutics may be beneficial in the most severe cases of COVID-19 to prevent fibrotic sequelae.…”

Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA 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(Hillary et al, , 2021. Evidence suggest that severe COVID-19 disease may impact certain epigenetic clocks (Mongelli et al, 2021;Corley et al, 2021) 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, 2021), with some finding no clock acceleration in COVID-19 patients (Franzen et al, 2021).…”