Association of Innate Immune Responses with SARS-CoV-2 Positivity in Children Under Five Years Old

Abstract

Introduction: The innate immune system detects viral RNA via RIG-I and MDA5, triggering type I interferon production. However, the effects of SARS-CoV-2 on these pathways in young children are still unclear. This study compared the expression of RIG-I, MDA5, IFN-α, and IFN-β between SARS-CoV-2-positive and SARS-CoV-2-negative children under five years of age with respiratory symptoms.
Materials and methods: This cross-sectional study included 138 children younger than five years who presented with respiratory symptoms, including fever, cough, and/or rhinorrhea, at Khanevadeh Hospital in Tehran, Iran, between April 6 and November 1, 2022. SARS-CoV-2 infection was identified using real-time reverse-transcription polymerase chain reaction (qRT-PCR) targeting the E and RDRP genes. The relative mRNA levels of RIG-I, MDA5, IFN-α, and IFN-β genes were measured using qRT-PCR, with GAPDH serving as the reference gene. The expression levels were then compared between children who tested positive and those who tested negative for SARS-CoV-2.
Results: Children who tested positive for SARS-CoV-2 had significantly higher IFN-α expression (0.06 ± 0.02 versus 0.04 ± 0.02) and significantly higher MDA5 expression (3.03 ± 1.10 versus 1.98 ± 0.56) than those who tested negative. IFN-β expression did not differ significantly between the two groups (0.07 ± 0.06 versus 0.07 ± 0.08). The RIG-I expression was numerically higher in SARS-CoV-2-positive children, but the difference was not statistically significant.
Conclusion: In children under five years of age with respiratory symptoms, SARS-CoV-2 positivity was linked to higher MDA5 and IFN-α expression, while RIG-I and IFN-β levels did not significantly differ between infected and uninfected participants. The current findings suggested that MDA5-related innate immune signaling may be involved in the early antiviral response to SARS-CoV-2 in young children.