Genetic Susceptibility to Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants

FEROLLA FM; ACOSTA PL; TOLEDANO, A; YFRAN, EW; GIORDANO, AC; CARATOZZOLO, A; CONTRINI, MM; LOPEZ EL

Congreso; American Thoracic Society 2019 International Conference; 2019

Background Differential expression of selected immunity genes may have a role in susceptibility to Respiratory Syncytial Virus (RSV). There are few data about some candidate gene single nucleotide polymorphisms (SNPs) associated with the severity of respiratory infections (e.g., Toll-like receptor 4 [TLR4], Toll-like receptor 8 [TLR8], macrophage receptor with colagenous structure [MARCO], myxovirus resistance 1 [MX1]). The aims of this study were to detect the presence of SNPs in selected genes of previously healthy infants infected with RSV, to assess viral load (VL) and to analyze their relationship with life-threatening disease (LTD)MethodsProspective cohort study including previously healthy full-term infants < 12 months, hospitalized with a first RSV infection during 2017?2018. RSV diagnosis, virus quantification and genotyping for SNPs (TLR4 rs4986790, TLR4 rs4986791, MARCO rs1318645, MX1 rs469390, TLR8 rs3761624) were performed by qRT?PCR in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit needing mechanical or non invasive ventilationResults75 patients, mean age 3.9 months (±2.8), 41 (54.7%) male. Fifteen developed LTD. Infants who were homozygous (−/−) or heterozygous (+/−) for MX1rs469390 and TLR8rs3761624 or MARCOrs1318645 and TLR8rs3761624 had significantly more risk of developing LTD (OR 3.45, P = 0.042; OR 3.63, P = 0.048, respectively). Multivariable logistic regression analysis showed that concurrent MARCOrs1318645, MX1rs469390 and TLR8rs3761624 SNPs increased the risk of LTD (aOR 4.7, P = 0.018), fig 1. These SNPs also associated with prolonged length of stay (LOS) (P = 0.026) and > 7 days of hypoxemia (P = 0.031). No differences were seen in VL of patients with LTD compared with those with better outcome (P = 0.737). No differences in VL were seen in patients with SNPs. VL did not correlate with LOS or days of hypoxemia. No other socioeconomic, pregnancy or infant variables associated with LTDConclusionTo the best of our knowledge, this is the first study assessing the presence of concurrent SNPs and their association with life-threatening disease in previously healthy infants with RSV infection. These findings provide evidence on the importance of the host and its immune response for the severity of RSV infection.