Figure 2.

Key Figure. Model of Memory versus Naïve T Cell Proportions as Potential Contributors to Severe Coronavirus Disease 2019 (COVID-19) in Adults.

We hypothesize that the higher proportion of memory versus naïve T cells in adults compared with children (A) may contribute to the extensive collateral tissue damage and cytokine storm observed in severely ill COVID-19 patients. (B) Substantially increased overactivation might be fueled by excessive trained innate immunity leading to a dysregulated release of cytokines by innate immune cells (primarily monocytes/macrophages) upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults; this phenomenon might be associated with bystander memory T cell activation, inefficient clonal expansion of SARS-CoV-2-specific T cells, and low viral clearance. In children, trained immunity would be presumably lower and naïve T cells predominant, with a progressive antiviral response reflecting clonal T cell expansion and efficient viral clearance. These phenomena might contribute to a regulated response that could lead to only minor tissue damage, not compromising the clinical response of infected children. This model remains hypothetical.