Here, we applied single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to comprehensively characterize the properties of peripheral blood mononuclear cells (PBMCs) in young and old adults. We also enrolled young and aged COVID-19 patients in the incipient stage and recovery stage to explore how age influenced the capacity for recovery and prognosis of COVID-19 infection and to better understand the influence of immune dysregulation in aging and infection. Our data revealed that aging promotes the polarization of TCs from naive and memory to effector, exhausted and regulatory subtypes and increases the numbers of late natural killer cells (NKs), age-associated B cells (BCs), inflammatory MCs, and dysfunctional dendritic cells (DCs). With single-cell paired T/B cell receptor sequencing (scTCR/BCR-seq), we uncovered decreased diversity and increased clonality of effector, cytotoxic and exhausted CD8+ TC subsets in TCs and age-associated B subsets in BCs with age. Notably, aging increased the expression of inflammation-related genes, senescence-related genes, and coronavirus susceptibility genes in specific cell subtypes. Most impressively, COVID-19 caused similar immune cell landscape changes to that of aging and further increased aging-induced immune cell polarization and upregulation of inflammatory genes. Increased SARS-CoV-2 susceptibility gene expression and inflammatory MCs and decreased TCs aggravate inflammatory storms and lymphopenia (Mehta et al., 2020; Merad and Martin, 2020; Zhou et al., 2020) and likely underlie the high susceptibility and mortality of old patients. Overall, this work expands our knowledge of aging via single-cell transcriptomic, proteomic and chromatin accessibility immune cell profiling and highlights critical nodes between the dysregulated immune system and infections that may serve to modulate the process of inflammaging.