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新型冠状病毒感染患者外周免疫反应与疾病严重程度的关系:一项横断面研究。

The relationship between peripheral immune response and disease severity in SARS-CoV-2-infected subjects: A cross-sectional study.

机构信息

Postgraduate Program in Pharmacy, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Division of Clinical Analysis, Flow Cytometry Service, University Hospital of the Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.

出版信息

Immunology. 2022 Apr;165(4):481-496. doi: 10.1111/imm.13457. Epub 2022 Mar 2.

Abstract

Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID-19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty-seven COVID-19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID-19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA-DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID-19 patients showed an increase in MPO, interleukin (IL)-12, IL-6, IL-10, and IL-8, accompanied by a reduction in IL-17A and NOx. IL-10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID-19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL-10 as a possible prognostic biomarker for COVID-19.

摘要

2019 年冠状病毒病(COVID-19)是一种由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的呼吸道感染,在大多数严重病例中表现为强烈的炎症反应和免疫失调。为了更好地阐明外周免疫系统变化与 COVID-19 严重程度之间的关系,本研究旨在评估中性粒细胞、单核细胞和树突状细胞(DC)外周亚群的频率和绝对数量,此外还定量评估了炎症介质的水平。157 名 COVID-19 患者分为轻症、中度、重症和危重症。通过流式细胞术评估细胞成分和循环细胞因子。通过比色法测量一氧化氮(NOx)和髓过氧化物酶(MPO)水平。COVID-19 患者表现为中性粒细胞增多,并出现紧急髓系细胞生成迹象。中度至危重症患者观察到单核细胞成分改变,经典单核细胞增加,非经典单核细胞减少,所有单核细胞亚型的 HLA-DR 表达减少,表明免疫抑制。中度至危重症患者的 DC,尤其是浆细胞样 DC,也大量减少。COVID-19 患者的 MPO、白细胞介素(IL)-12、IL-6、IL-10 和 IL-8 增加,同时 IL-17A 和 NOx 减少。IL-10 水平≥14 pg/ml 与最差结局密切相关,其敏感性为 78.3%,特异性为 79.1%。本研究结果表明 COVID-19 存在全身效应,这些效应似乎与疾病的病理生理学有关,突出了 IL-10 作为 COVID-19 可能的预后生物标志物的潜力。

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