Plasma IL-15 levels discriminate symptomatic and asymptomatic mild COVID-19
Having observed distinct depletion profiles of CD4+ and CD8+ T cells, the relative sparing of CD8+ effector memory T cells and non T cell lymphopenia (B and NK cells) we surmised that IL-15, a major homeostatic and activation cytokine for these subsets needed to be evaluated in COVID-19 pathogenesis. We observed elevated levels of circulating IL-15 in lymphopenic, hypoxemic individuals and remarkably, as shown in Figure 3A, in symptomatic mild but not asymptomatic patients. All hypoxemic individuals had detectable levels of IL-15 followed by 70% of individuals with symptomatic infection and only 18% (2 out of 11) with asymptomatic infection (Figure 3B). Indeed, of the 2 asymptomatic individuals that had detectable levels of IL-15 at sampling, one later progressed to hypoxemia. No individuals within the SN control group had detectable levels of plasma IL-15. Underlying a strong role for this cytokine, possibly related to homeostatic repopulation in lymphopenia we observed significant negative correlations between depleted subsets and circulating IL-15 levels across all groups of COVID-19 affected individuals (Figure 3C-H and Supplementary Figure S4). Also, as observed for IL-6, sMAdCAM levels were negatively correlated with those of IL-15 (Figure 3I).
Finally, in a rudimentary analysis, we evaluated the possible prognostic value of our single determinations of IL-15 together with IL-6 and sMAdCAM in predicting duration of hospitalization independently. For this analysis, days of hospitalization post sampling, including those from individuals with undetectable values for these markers (considered as 0) were plotted as shown in Figure 3J-L. Participants were grouped into Low and High categories based on median values of these markers. Proportional hazards analysis revealed significantly longer hospitalization for individuals in the High IL-15 and IL-6 groups. This value was above >4.20 pg/ml of IL-15 and >14.39 pg/ml for IL-6.