Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction
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...
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MDPI AG
2025-01-01
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| author | Beatrice Spedicati Alessandro Pecori Maria Pina Concas Aurora Santin Romina Ruberto Giuseppe Giovanni Nardone Andrea D’Alessandro Giancarlo Tirelli Paolo Boscolo-Rizzo Giorgia Girotto |
| author_facet | Beatrice Spedicati Alessandro Pecori Maria Pina Concas Aurora Santin Romina Ruberto Giuseppe Giovanni Nardone Andrea D’Alessandro Giancarlo Tirelli Paolo Boscolo-Rizzo Giorgia Girotto |
| author_sort | Beatrice Spedicati |
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| description | 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 <i>ACE2</i> gene is associated with a worse olfactory performance, while an increased gene score in the <i>IFI44</i> and <i>NDUFAF4</i> 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 <i>ACE2</i> 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 <i>IFI44</i> and <i>NDUFAF4</i> 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. |
| format | Article |
| id | doaj-art-9bd7ed9cbf7649f6bcd5948f0e28b076 |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-9bd7ed9cbf7649f6bcd5948f0e28b0762025-01-24T13:38:36ZengMDPI AGLife2075-17292025-01-011515610.3390/life15010056Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory DysfunctionBeatrice Spedicati0Alessandro Pecori1Maria Pina Concas2Aurora Santin3Romina Ruberto4Giuseppe Giovanni Nardone5Andrea D’Alessandro6Giancarlo Tirelli7Paolo Boscolo-Rizzo8Giorgia Girotto9Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyInstitute for Maternal and Child Health, I.R.C.C.S. “Burlo Garofolo”, 34137 Trieste, ItalyInstitute for Maternal and Child Health, I.R.C.C.S. “Burlo Garofolo”, 34137 Trieste, ItalyInstitute for Maternal and Child Health, I.R.C.C.S. “Burlo Garofolo”, 34137 Trieste, ItalyInstitute for Maternal and Child Health, I.R.C.C.S. “Burlo Garofolo”, 34137 Trieste, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, ItalyCOVID-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 <i>ACE2</i> gene is associated with a worse olfactory performance, while an increased gene score in the <i>IFI44</i> and <i>NDUFAF4</i> 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 <i>ACE2</i> 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 <i>IFI44</i> and <i>NDUFAF4</i> 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.https://www.mdpi.com/2075-1729/15/1/56COVID-19post-viral olfactory dysfunctionWhole Genome Sequencingrare variantscommon variants |
| spellingShingle | Beatrice Spedicati Alessandro Pecori Maria Pina Concas Aurora Santin Romina Ruberto Giuseppe Giovanni Nardone Andrea D’Alessandro Giancarlo Tirelli Paolo Boscolo-Rizzo Giorgia Girotto Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction Life COVID-19 post-viral olfactory dysfunction Whole Genome Sequencing rare variants common variants |
| title | Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction |
| title_full | Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction |
| title_fullStr | Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction |
| title_full_unstemmed | Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction |
| title_short | Scent of COVID-19: Whole-Genome Sequencing Analysis Reveals the Role of <i>ACE2</i>, <i>IFI44</i>, and <i>NDUFAF4</i> in Long-Lasting Olfactory Dysfunction |
| title_sort | scent of covid 19 whole genome sequencing analysis reveals the role of i ace2 i i ifi44 i and i ndufaf4 i in long lasting olfactory dysfunction |
| topic | COVID-19 post-viral olfactory dysfunction Whole Genome Sequencing rare variants common variants |
| url | https://www.mdpi.com/2075-1729/15/1/56 |
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