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中度新冠肺炎患者血液单核细胞和中性粒细胞的吞噬活性以及细菌裂解物免疫疗法的影响

Phagocytic activity of blood monocytes and neutrophils in moderate COVID-19 patients and impact of immune therapy with bacterial lysates.

作者信息

Kostinov Mikhail, Svitich Oksana, Chuchalin Alexander, Gajnitdinova Viliya, Bisheva Irina, Skhodova Svetlana, Osiptsov Valerij, Tatevosov Vitalij, Kryukova Nadezhda, Khrapunova Isabella, Cherdantsev Alexander, Soloveva Irina, Akhmatova Nelli, Kurbatova Ekaterina, Polishchuk Valentina, Kostinova Aristitsa, Vlasenko Anna, Loktionova Marina, Poddubikov Arseniy

机构信息

I. Mechnikov Research Institute of Vaccines and Sera, Moscow, Russian Federation.

I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.

出版信息

PLoS One. 2025 Jun 5;20(6):e0324987. doi: 10.1371/journal.pone.0324987. eCollection 2025.

Abstract

BACKGROUND

Monocytes, macrophages and dendritic cells are involved in phagocytic reactions, which potentially play an important role in the pathogenesis of COVID-19. Imbalance of these cells in peripheral blood has proven to affect not only innate but also adaptive immunity. It is possible that a search for strategies to restore monocyte activity could be a major step in achieving immune control over COVID-19. The aim of this study was to investigate the relationship between phagocytic activity of peripheral-blood monocytes and neutrophils, and COVID-19 severity, to assess the effects of a bacteria-based immunostimulating agent on phagocytosis parameters in in-hospital COVID-19 patients.

MATERIALS AND METHODS

The study included 105 adult patients with moderate COVID-19, who had been hospitalized in 2020-2021 and treated in accordance with the recommendations of the Ministry of Health of the Russian Federation. All patients were divided into two groups: in Group 1 patients received standard treatment and Immunovac VP4 therapeutic vaccine, a bacteria-based immunostimulating agent as add-on therapy from Day 1 of hospitalization; in Group 2 patients did not receive any add-on treatment. The study parameters included C-reactive protein (CRP), aspartate aminotransferase (AST), SpO2, lung involvement on chest computer tomography (CT) scan, and phagocytic activity of peripheral-blood leukocytes based on the absorption activity (AA) of monocytes and neutrophilic granulocytes against S. аureus). The parameters were assessed at 1, 14 and 30 days.

RESULTS

Based on a cluster analysis of the clinical findings and the results of diagnostic tests obtained on admission, the patients were divided into 2 clusters: cluster 1 including patients with a more severe disease (n = 34) and cluster 2 including patients with a less severe disease (n = 71). Cluster 1 patients had higher levels of CRP (20.1 vs. 2.2 mg/mL, p < 0.001), AST (32.9 vs. 26.2 U/L, p = 0.003), lower SpO2 (94% vs. 96%, p < 0,001) and more extensive lung involvement on chest CT scan (35% vs. 12%, p < 0,001). There was a statistically significant direct correlation between blood monocyte AA and SpO2 (p = 0.04), an inverse correlation between monocyte AA and CRP (p = 0.003) and the extent of lung involvement on CT scan (p = 0.05). In less severe COVID-19 patients (cluster 2), no statistically significant correlation was observed. In more severe COVID-19 patients (cluster 1), there was a rise in monocyte AA on day 30 of hospitalization both in the control group (from 86.6 to 92.2, p = 0.03) and the main group, who received Immunovac VP4 add-on therapy (from 87.3 to 98.3, p = 0.05). However, the patients who received the immunostimulating agent, had higher monocyte PI than the controls, without the immunostimulant (p = 0.05). Patients from cluster 1 who were given Immunovac VP4 had higher SpO2 levels (98% vs. 97%, p = 0.01) than those who had received only the standard treatment.

DISCUSSION

Blood monocyte AA correlates with COVID-19 severity: patients with less severe disease have higher AA and those with more severe illness have lower AA. The standard treatment, combined with Immunovac VP4 enhances phagocytic activity of peripheral-blood monocytes, which is associated with a more marked increase in SpO2, especially in more severe patients.

摘要

背景

单核细胞、巨噬细胞和树突状细胞参与吞噬反应,这可能在2019冠状病毒病(COVID-19)发病机制中发挥重要作用。外周血中这些细胞的失衡已被证明不仅会影响固有免疫,还会影响适应性免疫。寻找恢复单核细胞活性的策略可能是实现对COVID-19免疫控制的重要一步。本研究旨在探讨外周血单核细胞和中性粒细胞的吞噬活性与COVID-19严重程度之间的关系,评估一种基于细菌的免疫刺激剂对住院COVID-19患者吞噬作用参数的影响。

材料与方法

本研究纳入105例中度COVID-19成年患者,这些患者于2020 - 2021年住院,并按照俄罗斯联邦卫生部的建议进行治疗。所有患者分为两组:第1组患者接受标准治疗,并从住院第1天起接受Immunovac VP4治疗性疫苗,一种基于细菌的免疫刺激剂作为附加治疗;第2组患者未接受任何附加治疗。研究参数包括C反应蛋白(CRP)、天冬氨酸转氨酶(AST)、血氧饱和度(SpO2)、胸部计算机断层扫描(CT)上的肺部受累情况,以及基于单核细胞和嗜中性粒细胞对金黄色葡萄球菌的吸收活性(AA)的外周血白细胞吞噬活性。在第1、14和30天评估这些参数。

结果

根据入院时的临床发现和诊断测试结果进行聚类分析,患者被分为2个聚类:聚类1包括病情较重的患者(n = 34),聚类2包括病情较轻的患者(n = 71)。聚类1患者的CRP水平较高(20.1对2.2mg/mL,p < 0.001)、AST水平较高(32.9对26.2U/L,p = 0.003)、SpO2较低(94%对96%,p < 0.001),胸部CT扫描显示肺部受累更广泛(35%对12%,p < 0.001)。血液单核细胞AA与SpO2之间存在统计学显著的正相关(p = 0.04),单核细胞AA与CRP之间存在负相关(p = 0.003),与CT扫描上的肺部受累程度存在负相关(p = 0.05)。在病情较轻的COVID-19患者(聚类2)中,未观察到统计学显著相关性。在病情较重的COVID-19患者(聚类1)中,住院第30天时,对照组(从86.6升至92.2,p = 0.03)和接受Immunovac VP4附加治疗的主要组(从87.3升至98.3,p = 0.05)的单核细胞AA均有所升高。然而,接受免疫刺激剂的患者的单核细胞吞噬指数(PI)高于未接受免疫刺激剂的对照组(p = 0.05)。给予Immunovac VP4的聚类1患者的SpO2水平(98%对97%,p = 0.01)高于仅接受标准治疗的患者。

讨论

血液单核细胞AA与COVID-19严重程度相关:病情较轻的患者AA较高,病情较重的患者AA较低。标准治疗联合Immunovac VP4可增强外周血单核细胞的吞噬活性,这与SpO2更显著的升高相关,尤其是在病情较重的患者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/533b/12140414/1ebe17f32cac/pone.0324987.g001.jpg

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