FIGURE 6.

Proposed mechanistic models for age‐biased COVID‐19 severity in aged individuals. Several age‐related pathophysiologic immune responses are associated with disease susceptibility and severity in COVID‐19: a) decreased lymphocyte count and elevated inflammatory markers (C‐reactive protein [CRP], D‐dimer, and neutrophil–lymphocyte ratio); b) elevated pro‐inflammation cytokines IL‐8, IL‐27, and IL‐6 in aged COVID‐19 patients; c) reduced abundance of naïve CD8 T cells with decreased expression of antiviral defense genes (i.e., IFITM3 and TRIM22) in aged individuals with severe COVID‐19; d) type I interferon deficiency is associated with SARS‐CoV‐2 viral load in aged individuals; e) elevated expression of SARS‐CoV‐2 entry factors (BSG and FURIN) and reduced expression of antiviral defense genes (IFNAR1, OAS1, IFIT1) in the secretory cells of critical COVID‐19 in aged individuals; f) strong TGF‐beta‐mediated immune–epithelial cell interactions (i.e., secretory—nrMa) in aged individuals with critical COVID‐19