Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G H Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Lorenz Kretschmer, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Peñalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat H Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering, Marina Botto, Sarah A Teichmann, Muzlifah Haniffa, Menna R Clatworthy, David C Thomas, James E Peters
{"title":"COVID-19在终末期肾脏疾病中的时间多组学分析","authors":"Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G H Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Lorenz Kretschmer, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Peñalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat H Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering, Marina Botto, Sarah A Teichmann, Muzlifah Haniffa, Menna R Clatworthy, David C Thomas, James E Peters","doi":"10.1016/j.xgen.2025.100918","DOIUrl":null,"url":null,"abstract":"<p><p>Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100918"},"PeriodicalIF":11.1000,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Temporal multi-omics analysis of COVID-19 in end-stage kidney disease.\",\"authors\":\"Emily Stephenson, Erin Macdonald-Dunlop, Lisa M Dratva, Rik G H Lindeboom, Zewen Kelvin Tuong, Win Min Tun, Lorenz Kretschmer, Norzawani B Buang, Stephane Ballereau, Mia Cabantaus, Ana Peñalver, Elena Prigmore, John R Ferdinand, Benjamin J Stewart, Jack Gisby, Talat H Malik, Candice L Clarke, Nicholas Medjeral-Thomas, Maria Prendecki, Stephen McAdoo, Anais Portet, Michelle Willicombe, Eleanor Sandhu, Matthew C Pickering, Marina Botto, Sarah A Teichmann, Muzlifah Haniffa, Menna R Clatworthy, David C Thomas, James E Peters\",\"doi\":\"10.1016/j.xgen.2025.100918\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.</p>\",\"PeriodicalId\":72539,\"journal\":{\"name\":\"Cell genomics\",\"volume\":\" \",\"pages\":\"100918\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell genomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xgen.2025.100918\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2025.100918","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Temporal multi-omics analysis of COVID-19 in end-stage kidney disease.
Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single-cell immune profiling of ESKD patients with COVID-19. Transcriptome, surface proteome, and immunoreceptor sequencing data were generated on 580,040 high-quality cells, derived from 187 samples from 61 patients. For a subset of individuals, we obtained samples before and during infection, allowing intra-individual comparison. Longitudinal profiling demonstrated distinct temporal gene expression trajectories in severe/critical versus mild/moderate COVID-19. We identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Evaluation of clonal T cell dynamics showed that the fastest expanding clones were enriched in known SARS-CoV-2-specific sequences and shared across multiple patients. Comparison with external datasets revealed upregulation of immune cell TGF-β pathway expression in ESKD, irrespective of COVID-19 status. Our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population.
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