Nadia Baalbaki, Jelle M Blankestijn, Samuel W Kazer, Mahmoud I Abdel-Aziz, Lizan D Bloemsma, Harm Jan Bogaard, Merel E B Cornelissen, Cornelis M van Drunen, Daniëlle van Egmond, Esther J Nossent, Jaclyn M L Walsh, Jose Ordovas-Montanes, Korneliusz Golebski, Anke H Maitland-van der Zee
{"title":"迈向精准医学：长冠状病毒的炎症性鼻上皮转录组谱。","authors":"Nadia Baalbaki, Jelle M Blankestijn, Samuel W Kazer, Mahmoud I Abdel-Aziz, Lizan D Bloemsma, Harm Jan Bogaard, Merel E B Cornelissen, Cornelis M van Drunen, Daniëlle van Egmond, Esther J Nossent, Jaclyn M L Walsh, Jose Ordovas-Montanes, Korneliusz Golebski, Anke H Maitland-van der Zee","doi":"10.1016/j.jaci.2025.05.023","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale and objectives: </strong>Little is known about the role of the nasal epithelium in long COVID. This study aimed to assess nasal epithelial transcriptomes of long COVID(LC) patients to unravel pathophysiological mechanisms for disease management.</p><p><strong>Methods: </strong>Medical data and transcriptomes were obtained from participants in the 'Precision Medicine for more Oxygen'(P4O2) COVID-19 cohort, at 3-6(n=40) and 12-18(n=15) months post-COVID. Cell type frequencies were estimated by deconvolution from a single-cell dataset. Hierarchical clustering identified transcriptomic clusters and cellular clusters from which differences in gene expression, gene set enrichment and pulmonary phenotypes were assessed. Functional validation was performed using CRISPR-Cas9 gene editing and in vitro assays in primary mutant nasal epithelium and gene expression comparisons were made to healthy controls(n=51).</p><p><strong>Results: </strong>At 3-6 and 12-18 months, transcriptomes associated with inflammatory pathways(padj<0.05). Transcriptomic and cellular clusters were identified and were related to inflammation and ciliogenesis(padj<0.05). Comparison of transcriptomes of patients with and without pulmonary radiological abnormalities resulted in 613 significantly differentially expressed genes(padj<0.05). Upregulated inflammatory genes were observed in patients with abnormalities. SMURF1 expression was significantly increased in patients with compared to those without abnormalities and healthy controls. SMURF1<sup>-/-</sup> mutant nasal epithelial cells produced significantly lower levels(p<0.05) of pro-inflammatory cytokines upon virus exposure compared to controls.</p><p><strong>Conclusion: </strong>Nasal epithelium in LC exhibits persistent inflammatory states. SMURF1 upregulation potentially contributes to an exacerbated inflammatory state in nasal epithelium of patients with radiological abnormalities. This study demonstrates the importance of understanding these inflammatory profiles within a clinical context and emphasizes the need for further assessment and validation of SMURF1's role in LC.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Towards precision medicine: inflammatory nasal epithelial transcriptomic profiles in long COVID.\",\"authors\":\"Nadia Baalbaki, Jelle M Blankestijn, Samuel W Kazer, Mahmoud I Abdel-Aziz, Lizan D Bloemsma, Harm Jan Bogaard, Merel E B Cornelissen, Cornelis M van Drunen, Daniëlle van Egmond, Esther J Nossent, Jaclyn M L Walsh, Jose Ordovas-Montanes, Korneliusz Golebski, Anke H Maitland-van der Zee\",\"doi\":\"10.1016/j.jaci.2025.05.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale and objectives: </strong>Little is known about the role of the nasal epithelium in long COVID. This study aimed to assess nasal epithelial transcriptomes of long COVID(LC) patients to unravel pathophysiological mechanisms for disease management.</p><p><strong>Methods: </strong>Medical data and transcriptomes were obtained from participants in the 'Precision Medicine for more Oxygen'(P4O2) COVID-19 cohort, at 3-6(n=40) and 12-18(n=15) months post-COVID. Cell type frequencies were estimated by deconvolution from a single-cell dataset. Hierarchical clustering identified transcriptomic clusters and cellular clusters from which differences in gene expression, gene set enrichment and pulmonary phenotypes were assessed. Functional validation was performed using CRISPR-Cas9 gene editing and in vitro assays in primary mutant nasal epithelium and gene expression comparisons were made to healthy controls(n=51).</p><p><strong>Results: </strong>At 3-6 and 12-18 months, transcriptomes associated with inflammatory pathways(padj<0.05). Transcriptomic and cellular clusters were identified and were related to inflammation and ciliogenesis(padj<0.05). Comparison of transcriptomes of patients with and without pulmonary radiological abnormalities resulted in 613 significantly differentially expressed genes(padj<0.05). Upregulated inflammatory genes were observed in patients with abnormalities. SMURF1 expression was significantly increased in patients with compared to those without abnormalities and healthy controls. SMURF1<sup>-/-</sup> mutant nasal epithelial cells produced significantly lower levels(p<0.05) of pro-inflammatory cytokines upon virus exposure compared to controls.</p><p><strong>Conclusion: </strong>Nasal epithelium in LC exhibits persistent inflammatory states. SMURF1 upregulation potentially contributes to an exacerbated inflammatory state in nasal epithelium of patients with radiological abnormalities. This study demonstrates the importance of understanding these inflammatory profiles within a clinical context and emphasizes the need for further assessment and validation of SMURF1's role in LC.</p>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2025-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jaci.2025.05.023\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2025.05.023","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Towards precision medicine: inflammatory nasal epithelial transcriptomic profiles in long COVID.
Rationale and objectives: Little is known about the role of the nasal epithelium in long COVID. This study aimed to assess nasal epithelial transcriptomes of long COVID(LC) patients to unravel pathophysiological mechanisms for disease management.
Methods: Medical data and transcriptomes were obtained from participants in the 'Precision Medicine for more Oxygen'(P4O2) COVID-19 cohort, at 3-6(n=40) and 12-18(n=15) months post-COVID. Cell type frequencies were estimated by deconvolution from a single-cell dataset. Hierarchical clustering identified transcriptomic clusters and cellular clusters from which differences in gene expression, gene set enrichment and pulmonary phenotypes were assessed. Functional validation was performed using CRISPR-Cas9 gene editing and in vitro assays in primary mutant nasal epithelium and gene expression comparisons were made to healthy controls(n=51).
Results: At 3-6 and 12-18 months, transcriptomes associated with inflammatory pathways(padj<0.05). Transcriptomic and cellular clusters were identified and were related to inflammation and ciliogenesis(padj<0.05). Comparison of transcriptomes of patients with and without pulmonary radiological abnormalities resulted in 613 significantly differentially expressed genes(padj<0.05). Upregulated inflammatory genes were observed in patients with abnormalities. SMURF1 expression was significantly increased in patients with compared to those without abnormalities and healthy controls. SMURF1-/- mutant nasal epithelial cells produced significantly lower levels(p<0.05) of pro-inflammatory cytokines upon virus exposure compared to controls.
Conclusion: Nasal epithelium in LC exhibits persistent inflammatory states. SMURF1 upregulation potentially contributes to an exacerbated inflammatory state in nasal epithelium of patients with radiological abnormalities. This study demonstrates the importance of understanding these inflammatory profiles within a clinical context and emphasizes the need for further assessment and validation of SMURF1's role in LC.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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