Spedicati Beatrice, Pecori Alessandro, Concas Maria Pina, Santin Aurora, Ruberto Romina, Nardone Giuseppe Giovanni, D'Alessandro Andrea, Tirelli Giancarlo, Boscolo-Rizzo Paolo, Girotto Giorgia
Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy.
Institute for Maternal and Child Health, I.R.C.C.S. "Burlo Garofolo", 34137 Trieste, Italy.
Life (Basel). 2025 Jan 5;15(1):56. doi: 10.3390/life15010056.
COVID-19-related persistent olfactory dysfunction (OD) presents remarkable interindividual differences, and little is known about the host genetic factors that are involved in its etiopathogenesis. The goal of this study was to explore the genetic factors underpinning COVID-19-related OD through the analysis of Whole Genome Sequencing data of 153 affected subjects, focusing on genes involved in antiviral response regulation. An innovative approach was developed, namely the assessment of the association between a "gene score", defined as the ratio of the number of homozygous alternative variants within the gene to its length, and participants' olfactory function. The analysis highlighted how an increased gene score in the gene is associated with a worse olfactory performance, while an increased gene score in the and genes is associated with a better olfactory function. Considering the physiological role of the proteins encoded by these genes, it can be hypothesized that a reduced expression of may be associated with a protracted and severe inflammatory response in the olfactory epithelium, thus worsening patients' smell abilities. Conversely, an increased gene score in and might be associated with a decreased inflammatory response, thus correlating with a better olfactory performance. Overall, this study identified new host genetic factors that may play a pivotal role in determining COVID-19-related OD heterogeneity, possibly enabling more personalized and effective clinical management for affected individuals.
与新冠病毒病相关的持续性嗅觉功能障碍（OD）存在显著的个体差异，而对于其发病机制中涉及的宿主遗传因素知之甚少。本研究的目的是通过分析153名受影响受试者的全基因组测序数据，探索与新冠病毒病相关的OD的遗传因素，重点关注参与抗病毒反应调节的基因。开发了一种创新方法，即评估“基因评分”（定义为基因内纯合替代变体数量与其长度的比值）与参与者嗅觉功能之间的关联。分析突出显示，基因的基因评分增加与嗅觉表现较差相关，而基因和基因的基因评分增加与较好的嗅觉功能相关。考虑到这些基因所编码蛋白质的生理作用，可以推测基因表达降低可能与嗅觉上皮中持久且严重的炎症反应相关，从而使患者的嗅觉能力恶化。相反，基因和基因的基因评分增加可能与炎症反应降低相关，从而与较好的嗅觉表现相关。总体而言，本研究确定了新的宿主遗传因素，这些因素可能在决定与新冠病毒病相关的OD异质性方面起关键作用，可能为受影响个体实现更个性化和有效的临床管理。
