Age is one of the most important risk factors that determines COVID-19 disease severity and mortality. The majority of deaths due to infection with SARS-CoV-2, the virus responsible for the COVID-19 pandemic, have occurred in patients aged 65 and older. The severity of disease and the inability to fight it off can, in part, be attributed to epigenetic dysregulation of an aging immune system.
Although the virus infects every age group, the disease severity and mortality rates are highest among older individuals. Eighty percent of COVID-19 patients admitted to the hospital were in the age group of 65 and above. COVID-19 death data were collected from over 45 countries and were reported as infection fatality ratio (IFR). The IFR across all the countries analyzed was close to zero for the 0-40 age group but differed vastly between countries for the age group of 65 and above. Despite the variation in numbers, the trend was the same between countries; being over the age of 65 was the highest predictor of COVID-19 patient mortality rate. This has been particularly significant in long-term care homes which so far contributed to 20 per cent of the deaths in Canada, Sweden and the United Kingdom.
As we age, our body acquires a plethora of epigenetic alterations, some of which result in a weakened immune system. These include, for example, DNA methylation alterations that lead to activation of autoimmune genes. In elderly patients, severe cases of COVID-19 often include acute lung injury and acute respiratory distress syndrome. Immune cells are directed to the sites of infection resulting in widespread inflammation and endothelial dysfunction in the lung, heart, kidneys, liver and brain.
In addition to an impaired immune response, elderly patients may be more susceptible to infection with the virus. RNA transcript analysis of lung tissue from healthy individuals showed that the epigenetic expression of the gene ACE2, which encodes the ACE2 receptor that SARS-CoV-2 uses to gain entry to the host cell, increases with age. Therefore, age-related dysregulation of ACE2 receptor levels could be a key factor fuelling the severity of COVID-19 symptoms.
Epigenetic processes play a key role in the progression of aging. A study of approximately 42,000 participants has shown that a person’s DNA methylation, which changes with age and is known as the “epigenetic clock”, could predict a person’s risk for disease and death. These findings suggest that the epigenetic clock may provide biomarkers (a measurable indicator of disease severity) for COVID-19 disease severity.
Apart from biological factors, psychosocial factors, such as stress of social distancing from loved ones, could promote worsening of symptoms in nursing home residents. Moreover, care homes that are filled to capacity increase the challenge of management and prevention of the spread.