A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals
IntroductionLong COVID is a debilitating condition that lasts for more than three months post-infection by SARS–CoV–2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450853/full |
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| author | Daniel Missailidis Esmaeil Ebrahimie Esmaeil Ebrahimie Manijeh Mohammadi Dehcheshmeh Claire Allan Oana Sanislav Paul Fisher Stephanie Gras Stephanie Gras Stephanie Gras Sarah J. Annesley |
| author_facet | Daniel Missailidis Esmaeil Ebrahimie Esmaeil Ebrahimie Manijeh Mohammadi Dehcheshmeh Claire Allan Oana Sanislav Paul Fisher Stephanie Gras Stephanie Gras Stephanie Gras Sarah J. Annesley |
| author_sort | Daniel Missailidis |
| collection | DOAJ |
| description | IntroductionLong COVID is a debilitating condition that lasts for more than three months post-infection by SARS–CoV–2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.MethodsIn this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.ResultsSeventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as ICOS (FDR p = 0.024) and S1PR1 (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors LILRB1 (FDR p = 0.005) and LILRB2 (FDR p = 0.027). PCA analysis demonstrated that LILRB1 and LILRB2 expression discriminated all of the Long COVID samples from COVID recovered samples.DiscussionDownregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. LILRB1 and LILRB2 should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-cf0b6f2b174548eaad3a4d2aaf8c0a3f2024-12-03T06:31:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14508531450853A blood-based mRNA signature distinguishes people with Long COVID from recovered individualsDaniel Missailidis0Esmaeil Ebrahimie1Esmaeil Ebrahimie2Manijeh Mohammadi Dehcheshmeh3Claire Allan4Oana Sanislav5Paul Fisher6Stephanie Gras7Stephanie Gras8Stephanie Gras9Sarah J. Annesley10Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, AustraliaGenomics Research Platform, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, AustraliaSchool of Animal and Veterinary Sciences, Faculty of Sciences, Engineering and Technology, University of Adelaide, Adelaide, SA, AustraliaGenomics Research Platform, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, AustraliaInfection & Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, AustraliaDepartment of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC, AustraliaIntroductionLong COVID is a debilitating condition that lasts for more than three months post-infection by SARS–CoV–2. On average, one in ten individuals infected with SARS CoV- 2 develops Long COVID worldwide. A knowledge gap exists in our understanding of the mechanisms, genetic risk factors, and biomarkers that could be associated with Long COVID.MethodsIn this pilot study we used RNA-Seq to quantify the transcriptomes of peripheral blood mononuclear cells isolated from COVID-recovered individuals, seven with and seven without Long COVID symptoms (age- and sex-matched individuals), on average 6 months after infection.ResultsSeventy genes were identified as significantly up- or down-regulated in Long COVID samples, and the vast majority were downregulated. The most significantly up- or downregulated genes fell into two main categories, either associated with cell survival or with inflammation. This included genes such as ICOS (FDR p = 0.024) and S1PR1 (FDR p = 0.019) that were both up-regulated, indicating that a pro-inflammatory state is sustained in Long COVID PBMCs compared with COVID recovered PBMCs. Functional enrichment analysis identified that immune-related functions were expectedly predominant among the up- or down-regulated genes. The most frequently downregulated genes in significantly altered functional categories were two leukocyte immunoglobulin like receptors LILRB1 (FDR p = 0.005) and LILRB2 (FDR p = 0.027). PCA analysis demonstrated that LILRB1 and LILRB2 expression discriminated all of the Long COVID samples from COVID recovered samples.DiscussionDownregulation of these inhibitory receptors similarly indicates a sustained pro-inflammatory state in Long COVID PBMCs. LILRB1 and LILRB2 should be validated as prospective biomarkers of Long COVID in larger cohorts, over time and against clinically overlapping conditions.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450853/fullCOVID-19Long COVIDbiomarkertranscriptomicsinflammationLILRB1 |
| spellingShingle | Daniel Missailidis Esmaeil Ebrahimie Esmaeil Ebrahimie Manijeh Mohammadi Dehcheshmeh Claire Allan Oana Sanislav Paul Fisher Stephanie Gras Stephanie Gras Stephanie Gras Sarah J. Annesley A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals Frontiers in Immunology COVID-19 Long COVID biomarker transcriptomics inflammation LILRB1 |
| title | A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals |
| title_full | A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals |
| title_fullStr | A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals |
| title_full_unstemmed | A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals |
| title_short | A blood-based mRNA signature distinguishes people with Long COVID from recovered individuals |
| title_sort | blood based mrna signature distinguishes people with long covid from recovered individuals |
| topic | COVID-19 Long COVID biomarker transcriptomics inflammation LILRB1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450853/full |
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