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A blood RNA transcriptome signature for COVID-19

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 f...

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Autores principales: Kwan, Philip Kam Weng, Cross, Gail B., Naftalin, Claire M., Ahidjo, Bintou A., Mok, Chee Keng, Fanusi, Felic, Permata Sari, Intan, Chia, Siok Ching, Kumar, Shoban Krishna, Alagha, Rawan, Tham, Sai Meng, Archuleta, Sophia, Sessions, October M., Hibberd, Martin L., Paton, Nicholas I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193593/
https://www.ncbi.nlm.nih.gov/pubmed/34116667
http://dx.doi.org/10.1186/s12920-021-01006-w
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author Kwan, Philip Kam Weng
Cross, Gail B.
Naftalin, Claire M.
Ahidjo, Bintou A.
Mok, Chee Keng
Fanusi, Felic
Permata Sari, Intan
Chia, Siok Ching
Kumar, Shoban Krishna
Alagha, Rawan
Tham, Sai Meng
Archuleta, Sophia
Sessions, October M.
Hibberd, Martin L.
Paton, Nicholas I.
author_facet Kwan, Philip Kam Weng
Cross, Gail B.
Naftalin, Claire M.
Ahidjo, Bintou A.
Mok, Chee Keng
Fanusi, Felic
Permata Sari, Intan
Chia, Siok Ching
Kumar, Shoban Krishna
Alagha, Rawan
Tham, Sai Meng
Archuleta, Sophia
Sessions, October M.
Hibberd, Martin L.
Paton, Nicholas I.
author_sort Kwan, Philip Kam Weng
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-021-01006-w.
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spelling pubmed-81935932021-06-11 A blood RNA transcriptome signature for COVID-19 Kwan, Philip Kam Weng Cross, Gail B. Naftalin, Claire M. Ahidjo, Bintou A. Mok, Chee Keng Fanusi, Felic Permata Sari, Intan Chia, Siok Ching Kumar, Shoban Krishna Alagha, Rawan Tham, Sai Meng Archuleta, Sophia Sessions, October M. Hibberd, Martin L. Paton, Nicholas I. BMC Med Genomics Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-021-01006-w. BioMed Central 2021-06-11 /pmc/articles/PMC8193593/ /pubmed/34116667 http://dx.doi.org/10.1186/s12920-021-01006-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kwan, Philip Kam Weng
Cross, Gail B.
Naftalin, Claire M.
Ahidjo, Bintou A.
Mok, Chee Keng
Fanusi, Felic
Permata Sari, Intan
Chia, Siok Ching
Kumar, Shoban Krishna
Alagha, Rawan
Tham, Sai Meng
Archuleta, Sophia
Sessions, October M.
Hibberd, Martin L.
Paton, Nicholas I.
A blood RNA transcriptome signature for COVID-19
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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193593/
https://www.ncbi.nlm.nih.gov/pubmed/34116667
http://dx.doi.org/10.1186/s12920-021-01006-w
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