Neutrophil proteomics identifies temporal changes and hallmarks of delayed recovery in COVID19
Neutrophil proteomics identifies temporal changes and hallmarks of delayed recovery in COVID19
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DOI：
10.1101/2022.08.21.22279031
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
M. Long;A. J. Howden;H. Keir;C. Rollings;Y. Giam;T. Pembridge;H. Abo-Leyah;A. Lloyd;G. S
中科院分区：
文献类型：
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作者：
M. Long;A. J. Howden;H. Keir;C. Rollings;Y. Giam;T. Pembridge;H. Abo-Leyah;A. Lloyd;G. S
基本原理：中性粒细胞在COVID 19的病理生理学中很重要，但SARS-CoV-2感染后导致中性粒细胞表型改变的分子变化尚未完全了解。目的：使用定量质谱为基础的蛋白质组学研究急性SARS-CoV-2感染后和恢复期中性粒细胞表型。方法：对PCR证实的SARS-CoV-2感染住院患者进行前瞻性观察研究（2020年5月至2020年12月）。患者在入院后96小时内入组，纵向采样长达29天。对照组包括非COVID 19急性下呼吸道感染（LRTI）和年龄匹配的未感染对照组。处理从外周血分离的中性粒细胞用于质谱分析。使用WHO顺序量表定义COVID 19严重程度和恢复。测量和主要结果：84名COVID 19患者被纳入，并与91名LRTI患者和42名对照进行比较。在COVID 19患者的中性粒细胞中，与未感染的对照组相比，鉴定了5，800种中性粒细胞蛋白质，其中1，748种蛋白质存在显著差异（q值<0.05），包括基线时的强干扰素应答，严重患者在入组后一周丢失。描述了与COVID 19疾病严重程度和长期疾病相关的中性粒细胞变化，并确定了调节中性粒细胞功能的候选靶点。COVID 19延迟恢复与代谢和信号蛋白、补体、趋化因子和白三烯受体、整合素和抑制性受体的变化有关。结论：SARS-CoV-2感染导致再循环中性粒细胞的持续存在，这些中性粒细胞具有不同的代谢特征和改变的对来自其他免疫细胞、病原体或细胞因子的迁移信号和线索作出反应的能力。
Rationale: Neutrophils are important in the pathophysiology of COVID19 but the molecular changes contributing to altered neutrophil phenotypes following SARS-CoV-2 infection are not fully understood. Objectives: To use quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes following acute SARS-CoV-2 infection and during recovery. Methods: Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May 2020-December 2020). Patients were enrolled within 96 hours of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID19 acute lower respiratory tract infection (LRTI) and age-matched non-infected controls. Neutrophils isolated from peripheral blood were processed for mass spectrometry. COVID19 severity and recovery were defined using the WHO ordinal scale. Measurements and Main Results: 84 COVID19 patients were included and compared to 91 LRTI patients and 42 controls. 5,800 neutrophil proteins were identified and 1,748 proteins were significantly different (q-value<0.05) in neutrophils from COVID19 patients compared to those of non-infected controls, including a robust interferon response at baseline, which was lost in severe patients one week after enrolment. Neutrophil changes associated with COVID19 disease severity and prolonged illness were characterized and candidate targets for modulation of neutrophil function were identified. Delayed recovery from COVID19 was associated with changes in metabolic and signalling proteins, complement, chemokine and leukotriene receptors, integrins and inhibitory receptors. Conclusions: SARS-CoV-2 infection results in the sustained presence of recirculating neutrophils with distinct metabolic profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.