Immune complexes as culprits of immunopathology in severe COVID-19.

IF 5.5 3区 医学 Q1 IMMUNOLOGY Medical Microbiology and Immunology Pub Date : 2023-04-01 Epub Date: 2022-07-23 DOI:10.1007/s00430-022-00743-8
Philipp Kolb, Sebastian Giese, Reinhard Edmund Voll, Hartmut Hengel, Valeria Falcone
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Abstract

Infection with the pandemic human coronavirus SARS-CoV-2 elicits a respiratory tract disease, termed Coronavirus disease 2019 (COVID-19). While a variable degree of disease-associated symptoms may emerge, severe COVID-19 is commonly associated with respiratory complications such as acute respiratory distress syndrome (ARDS), the necessity for mechanical ventilation or even extracorporeal membrane oxygenation (ECMO). Amongst others, disease outcome depends on age and pre-existing conditions like cardiovascular diseases, metabolic disorders but also age and biological sex. Intriguingly, increasing experimental and clinical evidence suggests that an exacerbated inflammatory response and in particular IgG immune complexes (ICs), significantly contribute to severe and prolonged COVID-19 disease progression. Vast amounts of deposited, unresolved ICs in tissue are capable to initiate an exaggerated Fc gamma receptor (FcγR) mediated signalling cascade which eventually results in common IC-associated organ diseases such as vasculitis, glomerulonephritis and arthritis, comorbidities that have been frequently reported for COVID-19. Moreover and independent of deposited ICs, very recent work identified soluble ICs (sIC) to be also present in the circulation of a majority of severely ill patients, where their systemic abundance correlated with disease severity. Thus, detection of circulating sICs in patients represents a potential marker for critical COVID-19 disease progression. Their detection early after clinical deterioration might become an indicator for the requirement of prompt anti-inflammatory treatment. Here, we review the role of ICs in COVID-19 progression, their possible origins and potential intervention strategies.

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免疫复合物是严重 COVID-19 免疫病理的罪魁祸首。
感染大流行的人类冠状病毒 SARS-CoV-2 会引发呼吸道疾病,称为冠状病毒病 2019(COVID-19)。虽然可能会出现不同程度的疾病相关症状,但严重的 COVID-19 通常会引起呼吸系统并发症,如急性呼吸窘迫综合征(ARDS)、机械通气甚至体外膜肺氧合(ECMO)。除其他因素外,疾病的预后取决于年龄和原有疾病,如心血管疾病、代谢紊乱,以及年龄和生理性别。耐人寻味的是,越来越多的实验和临床证据表明,炎症反应的加剧,尤其是 IgG 免疫复合物(ICs),在很大程度上导致了严重和持久的 COVID-19 疾病进展。组织中大量沉积、未溶解的 IC 能够启动 Fcγ 受体(FcγR)介导的信号级联,最终导致常见的 IC 相关器官疾病,如血管炎、肾小球肾炎和关节炎,这些都是 COVID-19 常见的合并症。此外,独立于沉积的 ICs,最近的研究发现可溶性 ICs(sIC)也存在于大多数重症患者的血液循环中,其系统丰度与疾病的严重程度相关。因此,在患者体内检测循环中的 sIC 是 COVID-19 重要疾病进展的潜在标志物。在临床病情恶化后及早检测到它们,可能会成为需要及时进行抗炎治疗的一个指标。在此,我们回顾了 ICs 在 COVID-19 进展中的作用、可能的起源和潜在的干预策略。
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来源期刊
CiteScore
10.60
自引率
0.00%
发文量
29
审稿时长
1 months
期刊介绍: Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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