Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect

Transient lymphopenia is a common feature of acute viral respiratory infections. The drastic and prolonged lymphopenia of COVID-19, however, is distinctive and largely stems from falling counts of T cells. This T-cell lymphopenia may contribute to the inordinate rise in COVID-19 mortality with older age, because naive T-cell clonal expansion is telomere length (TL)-dependent and TL of hematopoietic cells shortens with age. Here we present a biologically plausible model that links naive T-cell clonal expansion capacity and age-dependent hematopoietic cell TL (HCTL) shortening to explain the T- cell shortfall and the high COVID-19 mortality in older adults. The model shows that an individual with average HCTL at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next eight years. The collapse coincides with the steep increase in COVID-19 mortality with age. As young adults tend to maintain their relative HCTL over their life course, individuals with above and below average HCTL respectively experience the drop in maximal T-cell clonal expansion capacity at older and younger ages. HCTL metrics may thus explain the vulnerability of older adults to COVID-19 and predict the capacity for T-cell clonal expansion following vaccination against the virus.