T Cell and Monocyte Telomere Length Dynamics in Patients with COVID-19

Summary: Severe lymphopenia, expressed in decreased numbers of CD4 and CD8 T cells, increases the risk of dying fromCOVID-19. Regardless of the underlying causes of the decline in T cells, replenishing their numbers throughmassive replication is likely vital for convalescence. Such a process depends on telomere length (TL), which canimpose a limit on T cell replication. The recovery from lymphopenia associated with COVID-19 might, therefore,stall in individuals with comparatively short telomeres, including older individuals, men, and those with cardio-metabolic disease. These individuals are more likely to have severe COVID-19 and die from the infection. Inaddition, short telomeres might contribute to a macrophage-mediated 'cytokine storm' in these patients. Thesubstantial inter-individual variation in TL from birth onwards means, however, that telomeres of some youngadults are as short as those of older adults. Despite their young age, such younger persons are also at increasedrisk for severe COVID-19-associated decreased number of T cells and increased number of dysfunctionalmacrophages. The aims of the project are to measure TL parameters in CD4/CD8 T cells and monocytes frompatients with mild and severe COVID-19, monitor their TL dynamics during the course of the disease, andexamine their relations with the levels of selected cytokines, previously shown to be elevated in patients withsevere COVID-19. Findings have the potential to identify adults of any age who are at increased risk of dyingfrom COVID-19, and guide therapeutic modalities to reverse COVID-19- associated decline in CD4/CD8 T cells,including agents that stimulate telomerase, the reverse transcriptase that lengthens telomeres.