Aging reprograms human immune cell landscape, and increases the susceptibility and vulnerability of COVID-19. Schematic illustrating the key innate and adaptive immune functional alterations identified in PBMCs influenced by aging and COVID-19. Young healthy individuals maintain homeostasis in immune system which could timely eliminate pathogen. Aging leads to the increase of monocytes (MCs) and the decrease of T cells (TCs) in the immune system. Aging promotes the polarization of TCs from naive and memory to effector, exhausted and regulatory subtypes and increases the numbers of late natural killer (NK) cells, age-associated B cells, inflammatory MCs, and dysfunctional dendritic cells (DCs). Moreover, aging induces increased expression of genes related to SARS-CoV-2 susceptibility, suggesting increased susceptibility in the elderly. Importantly, aging induces DCs to lose the antigen-presenting ability, and turn to an inflammatory state. Together, a dysregulated immune system and increased expression of genes associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly