A blood RNA transcriptome signature for COVID-19
Abstract Background COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has no...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-021-01006-w |
| _version_ | 1831715429950685184 |
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| author | Philip Kam Weng Kwan Gail B. Cross Claire M. Naftalin Bintou A. Ahidjo Chee Keng Mok Felic Fanusi Intan Permata Sari Siok Ching Chia Shoban Krishna Kumar Rawan Alagha Sai Meng Tham Sophia Archuleta October M. Sessions Martin L. Hibberd Nicholas I. Paton |
| author_facet | Philip Kam Weng Kwan Gail B. Cross Claire M. Naftalin Bintou A. Ahidjo Chee Keng Mok Felic Fanusi Intan Permata Sari Siok Ching Chia Shoban Krishna Kumar Rawan Alagha Sai Meng Tham Sophia Archuleta October M. Sessions Martin L. Hibberd Nicholas I. Paton |
| author_sort | Philip Kam Weng Kwan |
| collection | DOAJ |
| description | Abstract Background COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. Methods We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. Results We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). Conclusions The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity. |
| first_indexed | 2024-12-21T00:18:33Z |
| format | Article |
| id | doaj.art-19b29319d2114df2ad82cc28aae4004c |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-21T00:18:33Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-19b29319d2114df2ad82cc28aae4004c2022-12-21T19:22:09ZengBMCBMC Medical Genomics1755-87942021-06-011411810.1186/s12920-021-01006-wA blood RNA transcriptome signature for COVID-19Philip Kam Weng Kwan0Gail B. Cross1Claire M. Naftalin2Bintou A. Ahidjo3Chee Keng Mok4Felic Fanusi5Intan Permata Sari6Siok Ching Chia7Shoban Krishna Kumar8Rawan Alagha9Sai Meng Tham10Sophia Archuleta11October M. Sessions12Martin L. Hibberd13Nicholas I. Paton14Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDivision of Infectious Diseases, Department of Medicine, National University Hospital, National University Health SystemDivision of Infectious Diseases, Department of Medicine, National University Hospital, National University Health SystemDivision of Infectious Diseases, Department of Medicine, National University Hospital, National University Health SystemDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Pharmacy, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of SingaporeAbstract Background COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. Methods We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. Results We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). Conclusions The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.https://doi.org/10.1186/s12920-021-01006-wSARS-CoV-2COVID-19Gene expressionBiomarkersRNA sequencingWhole blood |
| spellingShingle | Philip Kam Weng Kwan Gail B. Cross Claire M. Naftalin Bintou A. Ahidjo Chee Keng Mok Felic Fanusi Intan Permata Sari Siok Ching Chia Shoban Krishna Kumar Rawan Alagha Sai Meng Tham Sophia Archuleta October M. Sessions Martin L. Hibberd Nicholas I. Paton A blood RNA transcriptome signature for COVID-19 BMC Medical Genomics SARS-CoV-2 COVID-19 Gene expression Biomarkers RNA sequencing Whole blood |
| title | A blood RNA transcriptome signature for COVID-19 |
| title_full | A blood RNA transcriptome signature for COVID-19 |
| title_fullStr | A blood RNA transcriptome signature for COVID-19 |
| title_full_unstemmed | A blood RNA transcriptome signature for COVID-19 |
| title_short | A blood RNA transcriptome signature for COVID-19 |
| title_sort | blood rna transcriptome signature for covid 19 |
| topic | SARS-CoV-2 COVID-19 Gene expression Biomarkers RNA sequencing Whole blood |
| url | https://doi.org/10.1186/s12920-021-01006-w |
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