726. Viral Genomic Load, Cytokine Profiles and Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants

Abstract

BackgroundData are controversial regarding the role of viral load and the host immune response in the severity of respiratory syncytial virus (RSV) infection. The objective of this study was t. o analyze the relationship between viral load (VL) and host cytokine responses with RSV life-threatening disease (LTD).MethodsProspective cohort study including previously healthy infants <12 months, hospitalized with a first RSV infection in 2017. Viral titers were assessed by qPCR and cytokine levels measured in nasopharyngeal aspirates obtained on admission. All patients with LTD were admitted to the intensive care unit.ResultsFifty-one patients, median age 3 months (IQR 2–4), 29(56.9%) male. Eight developed LTD (1,569 LTD cases/10,000 RSV-hospitalizations/year [95% CI 702–2.859]). Antibiotic prescription was significantly higher (42.9 vs. 87.5%, P < 0.001) and length of hospitalization significantly prolonged (5.2 ± 1.9 vs. 16.1 ± 12.7 days, P < 0.001) in infants with LTD. No differences were seen in the number of amplification cycles needed for a positive qPCR test (CT) nor in the viral titers of patients with LTD compared with those with better outcome (P = 0.71), Figure 1. VL was not a predictor of LTD (AUC = 0.53); however, no LTD was seen with ≤159,200 copies/mL. CT/VL did not correlate with other outcomes (Figure 2). IFN-y levels (Th1 response) were significantly lower in infants with LTD (P = 0.034). We detected no differences in TNF-α (pro-inflammatory), IL-9, IL-13 (Th2), IL-10 or IL-17 (regulatory) levels from mildly/severely or extremely severe ill patients; lower IL-5 levels were seen in LTD (Figure 3). VL correlated with TNF-α (P < 0.001) and IL-10 (P < 0.001) levels. After logistic regression analysis, socioeconomic, pregnancy and infant variables showed no association with bad outcomes; only frequent consumption of fruits and vegetables during pregnancy conferred protection (aOR 0.03; P < 0.001).ConclusionRSV titers did not correlate with LTD. Lower levels of IFN-γ were associated with increased disease severity.These findings could provide additional data for future RSV preventive and therapeutic strategies. Disclosures All authors: No reported disclosures.