611: HOST IMMUNE ENDOTYPING IN PEDIATRIC ACUTE RESPIRATORY FAILURE

Abstract

Introduction: Acute respiratory failure (ARF) is a common reason for admission to the pediatric intensive care unit (PICU). The ability to immune endotype critically ill children with ARF to understand if adaptive or innate defects belie severity of illness, and then modulate these defects by evaluating therapies in an ex vivo fashion may be paradigm shifting. We have previously shown that T-cell IFN-γ (adaptive) and monocyte TNF-α (innate) production, as quantitated by the Enzyme-Linked Immune Absorbent Spot (ELISpot) assay, reflect immune competence in COVID-19 pneumonia, and illness severity is associated with decreased circulating lymphocytes with innate and adaptive immune suppression, evidenced by decreased IFN-ɣ and TNF-α production. This promising approach may have significant benefits in critically ill children, as it is unknown if specific measures of innate and adaptive immune function correlate with illness severity. We hypothesize that serial quantitative analysis of IFN-γ and TNF-α production by ELISpot will accurately reflect host immune status in critically ill children with ARF. Methods: In this IRB approved prospective cohort study, children admitted to the PICU with ARF had serial blood analysis using ELISpot for IFN-γ and TNF-α production after positive stimulus with CD3/28 and LPS respectively. ELISpot reporting for cytokine production is done as number of cells secreting the relevant cytokine; data was compared to relevant patient metadata and clinical outcomes. Results: We are currently enrolling patients, and have analyzed two patients with ARF secondary to pneumonia. Patient 1 had 19 cells secreting IFN-ɣ on day 1 and 69 cells on day 5; and 582 cells secreting TNF-α on day 1 and 1217 cells on day 5. Patient 2 had 18 cells secreting IFN-ɣ on day 1 and 144 cells on day 5; and 189 cells secreting TNF-α on day 1 and 466 cells on day 5. Conclusions: Preliminary analysis of IFN-γ and TNF-α production by ELISpot shows surprisingly more IFN-γ reduction early in disease course, which may be a driver of viral replication and severity of illness. Over 5 days, both patients had appropriately hyper inflammatory innate responses. With improved power and additional time points, there is potential to introduce adaptive stimulants early in disease trajectory that may alter clinical outcomes.