Timing is crucial for many aspects of life, and now, a rather timely study demonstrates that the acceleration of our epigenetic clocks after SARS-CoV-2 infection significantly impacts our risk of suffering severe COVID-19 and post-COVID-19 syndrome (“long COVID”).
Previous research has described how older patients suffer from a higher risk of developing severe COVID-19 (independent of age-related comorbidities) and that shorter telomeres associate with severe COVID-19. Furthermore, studies have linked SARS-CoV-2 infections to altered DNA methylation, while others have begun to tease apart a link between DNA methylation-based epigenetic age upon SARS-CoV-2 infection with disease severity. Therefore, the time kept by our epigenetic clocks likely represents an important, if underappreciated, factor influencing COVID-19 progression, severity, and recovery after SARS-CoV-2 infection.
These early findings led researchers headed by Huichuan Yu (Sun Yat-sen University, China) to compare the epigenetic ages of healthy and COVID-19 patients, as measured using DNA methylation profiles from the EPIC methylation array and five epigenetic clocks (Hannum, Horvath, PhenoAge, skinHorvath, and GrimAge), with their chronological age to explore potential associations with SARS-CoV-2 infection risk/COVID-19 severity.
Time flies, so let’s quickly hear how Cao and colleagues provided evidence that SARS-CoV-2 infection and COVID-19 severity may be a battle against the epigenetic clock:
- While epigenetic clock scores derived from the analysis of patient blood samples correlate robustly with chronological age, SARS-CoV-2 infection prompts significant acceleration of epigenetic aging
- Patients with non-severe and severe COVID-19 exhibit greater epigenetic age acceleration than healthy patients
- Severe COVID-19 patients also exhibit more epigenetic age acceleration than non-severe patients
- Pneumonia development in COVID-19 patients associates with significantly accelerated epigenetic aging
- Telomere shortening (measured with a telomere length estimator) parallels accelerated epigenetic aging (being shorter in progressively more severe COVID-19 cases)
- Telomere attrition may combine with accelerated epigenetic aging to influence long COVID risk
- DNA methylation profiling from all phases between infection and recovery provides evidence for a partial reversal of SARS-CoV-2 infection-induced accelerated epigenetic aging at late clinic phases in some patients
Just in time, the authors report how our epigenetic clocks speed up after SARS-CoV-2 infection, with the rate that epigenetic clocks spin in patients linked to COVID-19 severity and the chances of suffering from long COVID. With this timely knowledge in hand, the team now proposes accelerated epigenetic aging as a predictive biomarker for severe COVID-19 cases and irreversible epigenetic aging as a biomarker for long COVID risk.
For more on the impact of epigenetic aging on SARS-CoV-2 risk and COVID-19 severity, see Nature Communications, April 2022.