探讨新冠后综合征患者症状特异性炎症细胞因子的特征。

INTRODUCTION: Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. METHODS: Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. RESULTS: The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. CONCLUSION: Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.

简介：新冠后综合征（PCS）的特点是症状表现具有多样性，其病理生理学机制尚不清楚。在此，我们旨在分析 PCS 患者的炎症细胞因子谱，并研究该谱与 PCS 患者的临床症状以及内皮功能之间的关系。

方法：本分析性研究纳入了 2021 年 4 月至 2021 年 12 月期间所有符合条件的 66 例 PCS 患者。通过流式细胞术定量检测 IFN-γ、IL-1α、IL-1β、IL-6、IL-8、IL-10、IL-12p70、IL-27、IP-10、MCP-1 和 TNF-α 等细胞因子的血清浓度。使用热探针评估微血管血流和反应性来探索内皮功能。根据每个 PCS 症状的存在情况进行了对比研究。

结果：患者的平均年龄为 55.9±16.2 岁，男女比例为 0.69。41 例（62%）患者急性感染病情严重。最常报告的症状是呼吸困难（67%）、疲劳（50%）和记忆力问题（32%）。57 例（86%）患者存在内皮功能障碍。大多数患者的 IP-10（100%）、IL-8（95%）、IFN-γ（95%）、MCP-1（80%）和 TNF-α（70%）水平升高。89%的研究对象血清中 IL-10 浓度低于检测下限。急性感染严重程度与 IL-10、MCP-1 和 IL-27 升高有关。IL-6 和 IL-27 水平升高与疲劳有关，而呼吸困难患者的 IL-8 浓度更高。IL-8 水平升高更常见于内皮功能严重受损的患者。

结论：我们的研究结果进一步支持 PCS 存在内皮功能障碍，并显示促炎细胞因子升高，同时 IL-10-抗炎反应受到抑制。此外，还出现了免疫临床表型，例如疲劳时由 IL-6 和 IL-27 介导的炎症表型，呼吸困难时由 IL-8 介导的炎症表型。识别免疫临床表型将有助于更好地理解 PCS 症状的病理生理学。