P-1556. IFITM3 Genetic Variant rs34481144 and Increased Risk of Hypoxemia in Children infected with Influenza

TL;DR

A genetic variant in the IFITM3 gene is linked to a higher risk of severe influenza in children, especially those needing oxygen therapy.

Contribution

This study identifies a specific IFITM3 SNP (rs34481144) associated with severe influenza in children.

Findings

The T allele of rs34481144 is strongly linked to severe influenza requiring oxygen therapy (p=0.0069, OR 12.83).

Children with the T allele had significantly lower oxygen saturation upon admission (p < 0.001).

No significant differences in viral load or sex distribution were found across genotypes.

Abstract

Influenza remains a major cause of pediatric morbidity and mortality worldwide. Several factors can increase the risk of severe disease. IFITM3 protein is a critical antiviral factor restricting influenza virus infection. The single nucleotide polymorphism (SNP) rs34481144 (C/T) in IFITM3 has been associated with impaired immune responses, including reduced airway CD8⁺ T cells. We aimed to determine whether the rs34481144 variant is associated with influenza infection severity in children.
*Mild = not requiring supplemental oxygen therapy; Severe = requiring of supplemental oxygen therapy.**Immunization status, including Influenza vaccination (mandatory and free of charge for all patients <2 years old, or older with comorbidities, according to national immunization schedule) was also assessed.***More than 3 persons per room.****Within 48 hours of the onset of symptomsCC: homozygous wild typeCT: heterozygousTT: homozygous for the alternative allele

*Mild = not requiring supplemental oxygen therapy; Severe = requiring of supplemental oxygen therapy.

**Immunization status, including Influenza vaccination (mandatory and free of charge for all patients <2 years old, or older with comorbidities, according to national immunization schedule) was also assessed.

***More than 3 persons per room.

****Within 48 hours of the onset of symptoms

CC: homozygous wild type

CT: heterozygous

TT: homozygous for the alternative allele

Prospective cohort study including children < 16 years old hospitalized with acute lower respiratory infection during 2019-2023 at the Ricardo Gutierrez Children´s Hospital. Patients who did not require supplemental oxygen therapy (SO2) were defined to have mild disease; severe cases were those who required SO2. Nasal aspirates were tested by RT-qPCR for RSV, rhinovirus, metapneumovirus, parainfluenza 3, influenza A & B. Viral quantification was estimated by RT-qPCR. DNA was isolated from samples for genotyping and IFITM3 mutations were assessed by allelic discrimination with pre-optimized assays and performed by RT-qPCR.

401 children were enrolled. 51 (13%) were positive for influenza. Of them, 27 (53%) were male, the median age was 12 months and 4 (8%) had underlying illness. All were infected with influenza A type. Thirty-nine (76%) had severe disease. Characteristics of the population are shown in Table 1.

To determine whether SNP rs344811 was associated with Influenza disease severity, genotype was compared between mild and severe groups. The need of SO2 was increased among carriers of the alternative allele (rs34481144 T-genotype), with a significant detrimental effect p=0.0069; OR 12.83; CI 1.50 to 19.26 (Table 2). Furthermore, patients carrying the alternative allele had significantly lower oxygen saturation on admission (p=< 0.001). No significant differences were observed in viral load or sex distribution across genotypes.

The IFITM3 rs34481144 T allele is strongly associated with increased risk of severe influenza A infection in children. These findings highlight the importance of host genetic factors in the clinical course of Influenza and suggest a potential role for genetic screening in risk stratification.

All Authors: No reported disclosures

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