2157. Low Interferon-γ and Interleukin-13 Levels in the Respiratory Tract are Related to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

Abstract Background The mechanisms of interindividual susceptibility to respiratory syncytial virus (RSV) are not clearly understood. Viral load (VL), an exaggerated immune response or T-helper 2 (Th2) bias were postulated as playing a role in the severity of RSV infection. We aimed to analyze VL, cytokine profiles and their association with life-threatening disease (LTD). Methods Prospective cohort study including previously healthy full-term infants < 12 months old, hospitalized with a first RSV infection in 2017-2019. Nasopharyngeal aspirates were performed on admission to assess VL (by qRT-PCR) and cytokines levels (using a Bioplex panel). Cytokines were grouped according to their functional classification: proinflammatory (TNF-α), regulatory (interleukin [IL]-10), Th1 (interfereron-γ [IFN-γ]), Th2 (IL-4, IL-5, IL-9, IL-13) and Th17 (IL-17a). Patients were defined to have LTD when required admittance to the intensive care units and ventilatory support. Results One hundred and nineteen patients were studied, 68 (57%) were male; median age was 3 months. Nineteen (16%) infants developed LTD, with no significant differences in socioeconomic, pregnancy and infant variables compared with other RSV cases. Virus subtypes were not related to LTD (p= 0.77). VL was not associated with LTD (p= 0.51). Patients with LTD had significantly lower levels of IFN-γ (mean 0.08 pg/ml [standard deviation -SD- 0.06] vs. 0.32 pg/ml [SD 0.4]; p= 0.001) and IL-13 (mean 0.03 pg/ml [SD 0.04] vs. 0.05 pg/ml [SD 0.07]; p= 0.02), fig 1. IFN-γ and IL-13 inversely correlated with days of hypoxemia (p< 0.001 and p= 0.002, respectively). VL, IFN-γ and IL-13 did not correlate with duration of symptoms before admission. No relationship was observed between IFN-γ, IL-13 and age, sex or breastfeeding. In 102 (86%) samples, IL-4 was under the limit of quantitation. TNF-α, IL-5, IL-9, IL-10 e IL-17a were not related to LTD. IFN-γ and interleukin-13 levels according to clinical outcome. Conclusion To our knowledge, this is the first study to relate low IL-13 levels to LTD in previously healthy infants. Patients with LTD had 4-fold lower levels of IFN-γ. The severity of RSV infection may be the result of a deficient immune response rather than a higher viral load or an overactive immune response. These findings provide additional evidence for the development of preventive and therapeutic strategies. Disclosures All Authors: No reported disclosures.