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.