Severe lymphopenia, expressed in decreased numbers of CD4 and CD8 T cells, increases the risk of dying from COVID-19. Regardless of the underlying causes of the decline in T cells, replenishing their numbers through massive replication is likely vital for convalescence. Such a process depends on telomere length (TL), which can impose 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. In addition, short telomeres might contribute to a macrophage-mediated ?cytokine storm? in these patients. The substantial inter-individual variation in TL from birth onwards means, however, that telomeres of some young adults are as short as those of older adults. Despite their young age, such younger persons are also at increased risk for severe COVID-19-associated decreased number of T cells and increased number of dysfunctional macrophages.
The aims of the project are to measure TL parameters in CD4/CD8 T cells and monocytes from patients with mild and severe COVID-19, monitor their TL dynamics during the course of the disease, and examine their relations with the levels of selected cytokines, previously shown to be elevated in patients with severe COVID-19. Findings have the potential to identify adults of any age who are at increased risk of dying from 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.
This pilot study focuses on the potential role of short telomeres in CD4/CD8 T Cells and monocytes in severe cases of COVID-19. We will measure telomere parameters in cells donated by patients admitted to the hospital with severe COVID-19 and compare findings in cells donated by outpatients with a mild form of the disease.
