The Severity of COVID-19 Infections Correlates to Telomere Length
The incidence of severe manifestations of COVID-19 increases with age with older patients showing the highest mortality. One mechanism of aging is the progressive shortening of telomeres, which are protective structures at chromosome ends. Critically short telomeres impair the regenerative capacity of tissues and trigger loss of tissue homeostasis and disease. The SARS-CoV-2 virus infects many different cell types, forcing cell turn-over and regeneration to maintain tissue homeostasis.
Now, Spanish researchers have found that find that shorter telomeres are associated with increased severity of the disease. Individuals within the lower percentiles of telomere length and higher percentiles of short telomeres have a higher risk of developing severe COVID-19 pathologies. These findings show that strategies to extend telomeres could be a potentially useful type of therapy in patients with remaining lung damage after COVID-19.
Treating COVID-19 as a Regenerative Disease
As we enter the second year of the COVID-19 pandemic, scientists have shifted their focus from trying to identify the causes of the infection, to understand how the virus works once an infection has been established. Approximately 80% of people who are exposed to the virus suffer mild flu-like symptoms once they become infected, whereas the remaining 20% develop a more severe form of the disease which can include respiratory complications, multi-organic failure, or even death.
Receptors for the virus are present in the lungs, the kidney, and the gut, which explains why these tissues are often compromised during infection. These sites of infection often heal but suffer irreversible scarring commonly referred to as fibrosis.
This permanent side effect led researchers to speculate that the viral infection may exhaust the regenerative and healing capacity of the infected cells. Adding to this is evidence that shows that infections are usually more severe in older individuals. Due to this, researchers have inferred that the severity of presentation and resulting complications are tied to the mechanisms of aging.
The Role of Telomeres in Aging
One such event is the age-related shortening of telomeres, a special structure present on the tips of chromosomes. Shortened telomeres lead to exhaustion of the proliferative potential of stem cells and immune cells, which has a direct effect on the body’s ability to fight the infection and prevent scarring from fibrosis.
These special structures act as protective end-caps to prevent genetic degradation, and also aid in the DNA repair process. During the normal process of aging, a small portion of the telomere is lost with each cell division.
Loss of telomere length speeds up cellular aging and can lead to apoptosis, or pre-programmed cellular death. Also, shorter telomeres are associated with an increased incidence of disease. Scientists have hypothesized that telomeres serve as a biological clock to determine the lifespan of a cell, and organisms (1). Telomeres are a key part of the natural aging process and a target for anti-aging therapies.
Telomerase is active in embryonic stem cells. However, after birth, telomerase is deactivated in most cells, causing telomeres to shorten with age. Previous studies have demonstrated that treatment with a special protein called telomerase, elongates telomeres. This has also been proposed as an anti-aging strategy (2).
During the first few weeks of the COVID-19 pandemic, a clear pattern of infections began to emerge among those affected. Younger patients seemed to develop milder symptoms, whereas older patients who were infected, tended to have more severe forms of the disease. There was a clear age-related component at play.
Study links severe COVID-19 disease to short telomeres
Due to this age-related connection, a group of Spanish researchers from the Spanish National Cancer Centre (CNIO), decided to examine the telomeres of infected patients to see if there was any correlation between telomere length and severity of COVID-19 infection. The results from their study have been recently published in the journal Aging (3).
“We know that the virus infects alveolar type II pneumocytes and that these cells are involved in lung regeneration; we also know that if they have telomeric damage they cannot regenerate, which induces fibrosis,” stated Dr. Maria Blasco, whose lab led the study. “This is what is seen in patients with lung lesions after COVID-19: we think they develop pulmonary fibrosis because they have shorter telomeres, which limits the regenerative capacity of their lungs.”
The study included 61 patients ranging in age from 29 to 85 that were classified according to the severity of their symptoms. A score of 1 was assigned to participants with a low fever and cough, while at the other end, a score of 4 was assigned to participants with features of Acute Respiratory Distress Syndrome (ARDS), or other severe complications that required treatment in an ICU.
Telomere length was assessed by extracting DNA from blood samples. Sanchez-Vazquez and colleagues first noted that a significant inverse correlation between mean telomere length as well as the percentage of short telomeres and age of the COVID-19 patients. also observed a significant direct correlation between the percentage of short telomeres, These findings confirm a significantly higher incidence of short telomeres with increasing age in the COVID-19 patients.
The study also found that there was an inverse correlation between telomere length and the severity of disease presentation. Shorter telomere lengths were associated with higher severity scores. There was also a direct correlation between age and severity of the disease. “Interestingly, we also found that those patients who have more severe COVID-19 pathologies have shorter telomeres at different ages compared to patients with milder disease,” stated the authors.
Interestingly, the researchers also observed that telomeres were consistently longer in female participants. This is in line with epidemiological data from the pandemic that shows that women infected with COVID-19 have overall lower mortality rates (4).
These findings suggest that patients infected with COVID-19 may have a higher risk of severe complications if their telomeres are shorter in length. Unfortunately, because shortening of telomeres is part of the natural aging process, older patients carry a higher risk when compared to the younger group of participants.
Possible Treatment through Anti-Aging Strategies
This study demonstrates that the shortening of telomeres, one of the hallmarks of aging, may influence the severity of COVID-19 infection. Therapies that aim to preserve telomere length, such as treatment with telomerase, may prove useful to prevent complications from COVID-19. Although these findings are promising, more research will be needed to determine if this strategy could be developed safely for use in humans.
- Shammas MA. Telomeres, lifestyle, cancer, and aging. Curr Opin Clin Nutr Metab Care. 2011;14(1):28-34. doi:10.1097/MCO.0b013e32834121b1
- Bernardes de Jesus B, Vera E, Schneeberger K, et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med. 2012;4(8):691-704. doi:10.1002/emmm.201200245
- Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco MA. Shorter telomere lengths in patients with severe COVID-19 disease [published online ahead of print, 2021 Jan 11]. Aging (Albany NY). 2021;12:10.18632/aging.202463. doi:10.18632/aging.202463
- COVID-19 Sex-Disaggregated Data Tracker available at: http://globalhealth5050.org/covid19
- Herrera E, Samper E, Martín-Caballero J, Flores JM, Lee HW, Blasco MA. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 1999;18(11):2950-2960. doi:10.1093/emboj/18.11.2950