Section of Paediatric Infectious Disease, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
Centre for Paediatrics and Child Health, Imperial College London, London, SW7 2AZ, UK.
Sci Rep. 2022 Jul 17;12(1):12216. doi: 10.1038/s41598-022-15547-2.
Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.
SARS-CoV-2 感染的临床表现高度可变，从无症状感染到危及生命的疾病都有。宿主全血转录组学可以为感染和疾病以及严重程度的生物学过程提供独特的见解。我们对不同严重程度 COVID-19 患者的全血 RNA 进行了测序。我们使用差异表达分析和通路富集分析来探索轻度、中度和重度 COVID-19 患者之间的血液转录组有何不同，并在组间进行两两比较。COVID-19 严重程度的增加以丰富的炎症免疫反应基因和通路为特征，包括许多与中性粒细胞和巨噬细胞相关的基因和通路，以及免疫球蛋白基因的上调。在这项研究中，我们首次展示了常用于 COVID-19 患者的免疫调节治疗如何极大地改变转录组。我们对 COVID-19 严重程度的研究揭示了免疫失调在向严重疾病进展中的作用，并强调需要进一步研究探索 SARS-CoV-2 与炎症免疫反应之间的相互作用。
