Li Jun, Shan Rui, Miller Heather, Filatov Alexander, Byazrova Maria G, Yang Lu, Liu Chaohong
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Cytek Biosciences, R&D Clinical Reagents, Fremont, CA 94538, USA.
Cell Insight. 2025 May 8;4(4):100250. doi: 10.1016/j.cellin.2025.100250. eCollection 2025 Aug.
The global COVID-19 pandemic has highlighted the pivotal role of the immune system in the development of severe respiratory symptoms, termed COVID-19 Severe Respiratory Syndrome (COVID-19-SR). This review aims to dissect the involvement of lung macrophages and monocytes in orchestrating immune responses to SARS-CoV-2, influencing disease severity and outcomes. Initially, we provide an overview of SARS-CoV-2's invasion process and the body's primary immune defense mechanisms, including the antibody complement system and cytokine production. We then delve into the roles of the monocyte-macrophage system in mediating hyperinflammation and cytokine storms, discussing how abnormal cytokine and chemokine levels contribute to disease progression. Subsequent sections examine the perturbations and overactivation of the monocyte-macrophage compartment during infection, linking these changes to the observed immune dysregulation in COVID-19 patients. In light of these insights, we explore therapeutic strategies targeting macrophages, such as dexamethasone, antisense lipid nanoparticles(ALN), and inhaled recombinant human granulocyte-macrophage colony-stimulating factor (rh-GM-CSF), which aim to modulate inflammation, suppress viral replication, and enhance viral clearance. Additional potential treatments include GSDMD inhibitors and GPR183 antagonists, which warrant further investigation. This review synthesizes current understanding of the immunopathology underlying COVID-19-SR, proposing macrophage- and monocyte-centered therapeutic avenues and outlining future research priorities essential for advancing clinical management and improving patient outcomes.
全球新冠疫情凸显了免疫系统在严重呼吸道症状（即新冠严重呼吸综合征，COVID-19-SR）发展过程中的关键作用。本综述旨在剖析肺巨噬细胞和单核细胞在协调针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的免疫反应、影响疾病严重程度和转归方面的作用。首先，我们概述SARS-CoV-2的入侵过程以及机体的主要免疫防御机制，包括抗体补体系统和细胞因子产生。接着，我们深入探讨单核细胞-巨噬细胞系统在介导过度炎症反应和细胞因子风暴中的作用，讨论细胞因子和趋化因子水平异常如何促进疾病进展。后续章节研究感染期间单核细胞-巨噬细胞区室的紊乱和过度激活，将这些变化与新冠患者中观察到的免疫失调联系起来。鉴于这些见解，我们探索针对巨噬细胞的治疗策略，如地塞米松、反义脂质纳米颗粒（ALN）和吸入重组人粒细胞-巨噬细胞集落刺激因子（rh-GM-CSF），其旨在调节炎症、抑制病毒复制并增强病毒清除。其他潜在治疗方法包括gasdermin D（GSDMD）抑制剂和GPR183拮抗剂，值得进一步研究。本综述综合了目前对COVID-19-SR免疫病理学的理解，提出以巨噬细胞和单核细胞为中心的治疗途径，并概述推进临床管理和改善患者转归所需的未来研究重点。
