CNIO studies have linked severe COVID-19 disease to short telomeres

Patients with severe COVID-19 disease have significantly shorter telomeres, according to a study conducted by researchers at the Spanish National Cancer Research Center (CNIO) in collaboration with the COVID-IFEMA field hospital. Published in Journal Aging.. The study, led by Maria A. Blasco and the first authors of Raúl Sánchez and Ana Guío-Carrión, hypothesized that shortening of telomeres as a result of viral infections impedes tissue regeneration, which is a significant number of patients. That’s why is suffering from long-term sequelae.

Blasco has already developed a treatment to regenerate lung tissue in patients with pulmonary fibrosis. She currently should take at least a year and a half before this treatment becomes available, but she believes it will also help those who have lung lesions after overcoming COVID-19.

Telomeres and tissue regeneration

The telomere and telomerase group, led by CNIO’s Blasco, has been studying the role of telomeres in tissue regeneration for decades. Telomeres are structures that protect the chromosomes in each cell of an organism. Telomere length is known to be an indicator of aging. Each time a cell divides, the telomere shortens to the point where it can no longer perform protective functions, and the damaged cell ceases to divide. Throughout life, cells are constantly dividing to regenerate tissue, and when cells stop dividing because telomeres are too short, the body ages.

In recent years, researchers have shown that it is possible to reverse this process in mice by activating the production of telomerase, an enzyme that prolongs telomeres. In animals, telomerase activation is effective in treating diseases associated with aging and telomere damage, such as pulmonary fibrosis.

COVID-19 as a reproductive disease

In pulmonary fibrosis, the lung tissue becomes scarred and hardened, resulting in a gradual loss of breathing ability. Previous studies have shown that one of the causes of the disease is damage to telomeres of alveolar type II alveolar epithelial cells, the cells involved in lung tissue regeneration. And these are exactly the cells that SARS-CoV-2 coronavirus infects lung tissue.

“When I read that type II alveolar lung cells were involved in COVID-19, I immediately suspected that telomeres were involved,” says Brasco.

In Aging’s treatise, the researchers wrote: “The general consequences of SARS-CoV-2 infection appear to be fibrosis-like phenotypic induction in the lungs and kidneys, suggesting that viral infections may be depleted. The ability of the organization to regenerate. ”

The authors suggest that it is the short telomeres that prevent tissue regeneration after infection. As Blasco explains, “I know that the virus infects alveolar type II alveolar epithelial cells and these cells are involved in lung regeneration, and cannot regenerate with telomere damage. It is also known to induce fibrosis. This is a lung lesion after COVID-19: It is thought to develop pulmonary fibrosis due to short telomeres and limited ability of the lungs to regenerate. ”

Field hospital patient sample

The data presented in the “Aging” paper provide evidence to support this hypothesis by finding an association between the higher severity of COVID-19 and shorter telomeres.

Despite the difficulties that arise from conducting research in the midst of a pandemic-“Hospital facilities for COVID-19 patients have been overwhelmed,” says Blasco-admitted to the IFEMA field hospital in Madrid89 It uses several techniques that have been able to analyze the telomeres of human patients.

As with the general population, the average telomere length decreased with increasing age in the patients studied. In addition, since the most severely ill patients are also the oldest, there is a correlation between high severity and short telomere length.

What was unforeseen, and the most important finding, is that telomeres in the most critically ill patients were also short, regardless of age.

The researchers wrote: “Interestingly, we also found that patients with more severe COVID-19 conditions had shorter telomeres at different ages than patients with milder illness.”

And they add: “These findings indicate that molecular features of aging, such as the presence of short telomeres, can affect the severity of COVID-19 pathology.”

Gene therapy for patients with lung injury after COVID-19

The researchers’ intention is to demonstrate a causal link between reduced telomere length and the pulmonary sequelae of COVID-19. To do this, they infect mice that have short telomeres and are unable to produce telomerase with SARS-CoV-2. Without telomerase, telomeres cannot be repaired and, as a result, lung tissue cannot be regenerated. If Blasco’s group hypothesis is correct, mice with short telomeres and no telomerase should develop more severe pulmonary fibrosis than normal mice.

Confirmation that short telomeres impede recovery in critically ill patients will open the door to new therapeutic strategies, such as treatments based on telomerase activation.

“Short telomerase can be lengthened again by telomerase, and given that previous studies have shown that telomerase activation has therapeutic effects on short telomere-related diseases such as pulmonary fibrosis, this treatment It is attractive to speculate that the method is possible to improve some of the remaining medical conditions in COVID-19 patients after the viral infection is overcome, such as pulmonary fibrosis. “

Last year, CNIO and the UAB of the Autonomous University of Barcelona established a new spin-off company, Telomere Therapeutics, with the particular aim of developing telomerase-based gene therapy for the treatment of various medical conditions associated with telomere shortening, such as the lungs. Did. Fibrosis and renal fibrosis. This is a type of treatment that may help patients with residual lung damage after COVID-19.