Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.
Gene expression refers to how often or when proteins are created from the instructions within your genes. While genetic changes can alter which protein is made, epigenetic changes affect gene expression to turn genes “on” and “off.” Since your environment and behaviors, such as diet and exercise, can result in epigenetic changes, it is easy to see the connection between your genes and your behaviors and environment.
One of the key features of Post-COVID Conditions, is that there is a wide spectrum of symptom clusters, across nearly every organ system; but individual patients do not present with all these symptoms. Thus, it is clear that there are underlying mechanisms at play leading to individuals presenting with these different symptom clusters. It is also likely that these distinct symptom clusters are not linked to the characteristics of the virus or infection or it's variants, but rather the individual's characteristics.
While there are obvious human characteristics that are risk factors for disease or severity of disease, such as obesity, comorbidities, age, and smoking status, these are most often linked to severity of acute infection. Post-acute sequelae, on the other hand, are seen more frequently in younger and healthier individuals, and can occur after mild and even asymptomatic COVID-19 infection. This suggests that there is a deeper underlying cause, and that the mechanisms of acute COVID-19 infection cannot be transferred to the post-acute phase.
Epigenome-wide studies of acute COVID-19 patients have found changes in things like DNA methylation, major histocompatibility factors, RNA regulation that have been shown to impact severity of disease. Thus, it is clear that COVID-19 shows signature epigenetic changes in patients during acute infection.
Current research is looking at how these epigenetic changes lead to post-acute sequelae and its observed symptom clusters.
Aging is a biological process related to diseases and mortality. Previous research has identified certain viral infections (including HIV, HBV, CMV) and bacterial infections can increase the rate at which the cells in the body age.
The biological process in aging is reflected by molecular hallmarks, which include epigenetic modifications and telomere shortening. DNA methylation correlates with aging process and can be used to estimate epigenetic aging across tissues. The deviation between DNA methylation age (DNAm age) and chronological age has been proposed as a biomarker for aging and has been related to risk and survival outcomes in age-related diseases.
In humans, telomere shortening is associated in the body with the aging process and, in the cells, with cellular replicative senescence (decreased cellular replication and cellular "death"). Telomeres possess properties that make them suitable as biomarkers in several diseases or conditions, including cancer, CVDs, and aging. The inverse correlation between telomere length (TL) and chronological age has been used for age prediction.
Interestingly, telomere length and the epigenetic clock do not correlate with one another, suggesting that DNAm age and TL measure different aspects of biological aging.
RNA viruses such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are capable of inducing immune dysfunction through hijacking host immune cell epigenomes and altering transcriptional programs to evade immune defenses. Epigenetics offers a window into understanding host‐pathogen interactions decoding the biologic dialogue between host and pathogen and understanding pathogen‐related disease outcomes.
Increasing evidence has shown that various components of the host immune system are dramatically altered during SARS‐CoV‐2 infection and the extent of immune dysregulation relates to severe COVID‐19 disease and mortality.
In order for SARS-CoV-2 to be successful in entering human cells and causing infections it must be able to continuously use the cell's metabolism machinery to replicate and invade. To do that it hijacks the host epigenetic mechanisms like DNA-methylation, acetylation, histone modifications etc.
