Determine whether the severity of SARS-CoV-2 infection with age is associated with a telomere dysfunction. – COST

This project is part of the “Physio-pathogeny of the disease” research axis, related to the development of cellular models to identify new therapeutic and prophylactic targets to fight SARS-CoV-2 infection. The diversity of symptoms and the various degrees of severity of the disease make the COVID-19 difficult to control. There is an urgent need to target the high-risk population.
A parallel can be drawn between the severity of SARS-CoV-2 infection and the biology of aging and we propose that COVID-19 can be considered as an age-related disease. Telomere dysfunction is a hallmark of aging and preliminary in vitro results showed that telomeres are protected by Dexamethasone. Dexamethasone is so far the best treatment for severely ill patients.

The objectives of our project are to show that: i) The higher vulnerability of some patients to severe SARS-CoV-2 infection is associated with telomere dysfunction and that ii) Treatment with Dexamethasone decreases patient mortality by reinforcing telomere protection, thus preventing cell senescence and aging. To meet these two objectives, we propose to analyze telomere maintenance i.e. DNA damage at telomeres, telomere length and senescence from blood samples of two cohorts of patients. We estimated at four months the time to collect the blood samples depending on the epidemic pressure, in collaboration with Pr Barbara Seitz-Polski and Pr Jean Dellamonica from the Archet 1 University Hospital, in Nice. We planned eight months to process and analyze the samples. The last month will include a general discussion with all the partners to analyze the results, to establish the main conclusions and to envision the perspectives.

In the short term, the results from the first objective, will help identify patients who are at high-risk due to the telomere and senescence status of their blood cells (PBMCs), providing a rational basis for the use of telomeres as biomarkers for the early detection and diagnosis of severe forms of SARS-CoV-2 infection. The knowledge generated in the second objective will provide a better understanding of the mechanism of action of Dexamethasone in COVID-19 patients and will tell us about the relevance of telomeres as targets for future therapies to treat COVID-19 patients.

Our results could improve the consequences of the current emergence of COVID-19, as well as the future emergence of new viruses or mutated ones with no available treatment. Our findings will also be transposable to all age-related diseases.