To depict how the immune landscape changes with aging and SARS-CoV-2 infection, we enrolled young (YCO, n = 2) and aged (ACO, n = 2) patients with incipient COVID-19 (to assess the acute inflammatory state) in cohort-2 and young (YCR, n = 2) and aged (ACR, n = 2) patients who had recovered from COVID-19 (to assess the recovered state) in cohort-3. In addition, we performed CyTOF analysis of PBMCs from YH, AH, YCO and ACO individuals in cohort-2 (n = 2 for each group) (Figs. 6A, S10 and S11). Similar to our CyTOF analysis in cohort-1, we identified 21 clusters: 9 subsets of TCs, 3 subsets of NKs, 4 subsets of BCs, 3 subsets of MCs, and 2 subsets of DCs (Figs. 6B and S11). We first compared the peripheral immune cell composition between COVID-19 patients (at the onset stage, CO) and their age-matched healthy controls (HC). Between the CO and HC groups, we found a similar trend of variation to aging, reflected in a decreased percentage of TCs and increased MC and NK populations (Fig. 6C–E). This trend was also observed at the cell subtype levels, as evidenced by decreased pDC, naive and memory TCs and BCs and increased populations of effector TCs, CD16 MCs, intermediate MCs, ASCs and ABCs (Figs. 6F, 6H, and S12A–L). Importantly, the aging-associated increase in MCs and decrease in TCs were amplified by COVID-19 in aged patients compared with healthy aged controls (Fig. 6I). This trend was also observed at the cell subtype level, as reflected by decreased naive TCs and BCs and increased populations of effector TCs, CD16 MCs, ASCs and ABCs in each immune cell composition and total circulating immune cells (Figs. 6J–N and S12M).
Figure 6 Poor outcomes upon COVID-19 infection is associated with imbalanced cellular aging. (A) t-SNE projections of PBMCs derived from mass cytometry data in cohort-2. (B) Heatmap showing mean population expression levels of all markers. (C) t-SNE plots segregated by HC and CO groups. HC includes YH (n = 2) and AH (n = 2); CO includes YCO (n = 2) and ACO (n = 2). (D) Percentage of immune cell populations in PBMC between HC (n = 4) and CO (n = 4) groups. (E) Bar chart of the relative percentage of major immune cell populations derived from mass cytometry data between HC and CO groups. (F) Percentage of CD4 Naive cells in CD45+ cells between HC (n = 4) and CO (n = 4) groups. (G) Percentage of NK2 cells in CD45+ cells between HC (n = 4) and CO (n = 4) groups. (H) Percentage of CD16 monocytes in CD45+ cells between HC (n = 4) and CO (n = 4) groups. (I) Bar chart of the relative percentage of major immune cells derived from mass cytometry data from YH, AH and ACO groups. (J) Bar chart of the relative percentage of T cell subsets derived from mass cytometry data from YH, AH and ACO groups. (K) Bar chart of the relative percentage of NK cell subsets derived from mass cytometry data from YH, AH and ACO groups. (L) Bar chart of the relative percentage of B cell subsets derived from mass cytometry data from YH, AH and ACO groups. (M) Bar chart of the relative percentage of DC subsets derived from mass cytometry data from YH, AH and ACO groups. (N) Bar chart of the relative percentage of monocyte subsets derived from mass cytometry data from YH, AH and ACO groups. (O) Bar chart of the relative percentage of major immune cell populations derived from mass cytometry data between YCO and ACO groups. (P) CT photography showing the different evolution of Lung Ground-Glass Opacity in young and aged patients with COVID-19. CT, computed tomography. P values are based on two-tailed Mann-Whitney-Wilcoxon tests between groups