Laboratoire d'Immunologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
Cellule d'Ingénierie des Données, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
Front Immunol. 2021 Sep 10;12:742446. doi: 10.3389/fimmu.2021.742446. eCollection 2021.
The SARS-CoV-2 infection triggers excessive immune response resulting in increased levels of pro-inflammatory cytokines, endothelial injury, and intravascular coagulopathy. The complement system (CS) activation participates to this hyperinflammatory response. However, it is still unclear which activation pathways (classical, alternative, or lectin pathway) pilots the effector mechanisms that contribute to critical illness. To better understand the immune correlates of disease severity, we performed an analysis of CS activation pathways and components in samples collected from COVID-19 patients hospitalized in Grenoble Alpes University Hospital between 1 and 30 April 2020 and of their relationship with the clinical outcomes.
We conducted a retrospective, single-center study cohort in 74 hospitalized patients with RT-PCR-proven COVID-19. The functional activities of classical, alternative, and mannose-binding lectin (MBL) pathways and the antigenic levels of the individual components C1q, C4, C3, C5, Factor B, and MBL were measured in patients' samples during hospital admission. Hierarchical clustering with the Ward method was performed in order to identify clusters of patients with similar characteristics of complement markers. Age was included in the model. Then, the clusters were compared with the patient clinical features: rate of intensive care unit (ICU) admission, corticoid treatment, oxygen requirement, and mortality.
Four clusters were identified according to complement parameters. Among them, two clusters revealed remarkable profiles: in one cluster (n = 15), patients exhibited activation of alternative and lectin pathways and low antigenic levels of MBL, C4, C3, Factor B, and C5 compared to all the other clusters; this cluster had the higher proportion of patients who died (27%) and required oxygen support (80%) or ICU care (53%). In contrast, the second cluster (n = 19) presented inflammatory profile with high classical pathway activity and antigenic levels of complement components; a low proportion of patients required ICU care (26%) and no patient died in this group.
These findings argue in favor of prominent activation of the alternative and MBL complement pathways in severe COVID-19, but the spectrum of complement involvement seems to be heterogeneous requiring larger studies.
SARS-CoV-2 感染引发过度免疫反应，导致促炎细胞因子水平升高、内皮损伤和血管内凝血功能障碍。补体系统（CS）的激活参与了这种过度炎症反应。然而，目前尚不清楚哪种激活途径（经典途径、替代途径或凝集素途径）启动了导致重症的效应机制。为了更好地了解疾病严重程度的免疫相关性，我们对 2020 年 4 月 1 日至 30 日期间在格勒诺布尔阿尔卑斯大学医院住院的 COVID-19 患者的样本中 CS 激活途径和成分进行了分析，并研究了它们与临床结局的关系。
我们进行了一项回顾性、单中心研究，纳入了 74 例经 RT-PCR 证实的 COVID-19 住院患者。在患者住院期间，测量了经典、替代和甘露聚糖结合凝集素（MBL）途径的功能活性以及 C1q、C4、C3、C5、因子 B 和 MBL 的抗原水平。采用 Ward 法的层次聚类对具有相似补体标志物特征的患者聚类。年龄包含在模型中。然后，将聚类与患者的临床特征进行比较：重症监护病房（ICU）入住率、皮质激素治疗、氧需求和死亡率。
根据补体参数确定了 4 个聚类。其中，两个聚类显示出显著的特征：在一个聚类（n=15）中，与其他所有聚类相比，患者的替代和凝集素途径被激活，MBL、C4、C3、因子 B 和 C5 的抗原水平较低；该聚类中死亡（27%）、需要吸氧（80%）或入住 ICU（53%）的患者比例较高。相比之下，第二个聚类（n=19）表现出炎症特征，经典途径活性高，补体成分的抗原水平高；该组入住 ICU 的患者比例较低（26%），且该组无患者死亡。
这些发现表明，严重 COVID-19 中替代和 MBL 补体途径的激活较为显著，但补体参与的范围似乎存在异质性，需要更大规模的研究。
