关键词: COVID-19 acute respiratory distress syndrome dysregulated immune response immune cells single-cell RNA sequencing

来  源:   DOI:10.3389/fcell.2023.1207960   PDF(Pubmed)

Abstract:
Introduction: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) and life-threatening multi-organ failure with increased levels of inflammatory mediators and viral load; however, little is known about its pathophysiology. Methods: To better understand the cellular status of COVID-19-induced ARDS, we performed single-cell RNA sequencing on peripheral blood samples from patients with COVID-19-induced ARDS. Single-cell RNA sequencing combined with bioinformatics analysis was used to study dynamic changes in cell composition and transcriptional profiles. Results: The single-cell RNA sequencing data revealed significant phenotypic differences between patients with COVID-19-induced ARDS and controls, mainly in monocytes, and CD8+ T and B cells. B-cell and monocyte abundances were significant in COVID-19-induced ARDS patients compared to controls, while CD8+ T cells were depleted. These data suggest that there is an imbalance between lymphocytes and monocytes in the blood of COVID-19-induced ARDS patients. In addition, cytokine interactions between T cells, monocytes and B cells are enhanced as evidenced by the intercellular communication analysis. In particular, T cell subsets target receptors on other cells via CCL5 and may play an important role in patients with COVID-19-induced ARDS. Conclusion: Our analysis suggested that a dysregulated adaptive immune response exists in patients with COVID-19-induced ARDS. Overall, we provided a cellular picture of the peripheral immune response in patients with COVID-19-induced ARDS.
摘要:
简介:2019年冠状病毒病(COVID-19)可导致急性呼吸窘迫综合征(ARDS)和危及生命的多器官衰竭,并增加炎症介质和病毒载量;然而,对其病理生理学知之甚少。方法:为了更好地了解COVID-19诱导的ARDS的细胞状态,我们对COVID-19诱导的ARDS患者的外周血样本进行了单细胞RNA测序.单细胞RNA测序结合生物信息学分析用于研究细胞组成和转录谱的动态变化。结果:单细胞RNA测序数据显示,COVID-19诱导的ARDS患者与对照组之间的表型差异显著,主要在单核细胞中,和CD8+T和B细胞。与对照组相比,COVID-19诱导的ARDS患者的B细胞和单核细胞丰度显著,而CD8+T细胞耗尽。这些数据表明,COVID-19诱导的ARDS患者血液中淋巴细胞和单核细胞之间存在失衡。此外,T细胞之间的细胞因子相互作用,细胞间通讯分析证明单核细胞和B细胞增强。特别是,T细胞亚群通过CCL5靶向其他细胞上的受体,可能在COVID-19诱导的ARDS患者中发挥重要作用。结论:我们的分析表明,COVID-19诱导的ARDS患者存在适应性免疫反应失调。总的来说,我们提供了COVID-19诱导的ARDS患者外周免疫反应的细胞图.
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