Complement Activation in the Disease Course of Coronavirus Disease 2019 and Its Effects on Clinical Outcomes

被引:91
作者
de Nooijer, Aline H. [1 ,2 ]
Grondman, Inge [1 ,2 ]
Janssen, Nico A. F. [1 ,2 ]
Netea, Mihai G. [1 ,2 ,3 ]
Willems, Loek [4 ]
van de Veerdonk, Frank L. [1 ,2 ]
Giamarellos-Bourboulis, Evangelos J. [5 ]
Toonen, Erik J. M. [4 ]
Joosten, Leo A. B. [1 ,2 ,6 ]
机构
[1] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Radboud Ctr Infect Dis, Med Ctr, Nijmegen, Netherlands
[3] Univ Bonn, Life & Med Sci Inst, Immunol & Metab, Bonn, Germany
[4] Hycult Biotechnol, R&D Dept, Uden, Netherlands
[5] Natl & Kapodistrian Univ Athens, Dept Internal Med 4, Athens, Greece
[6] Fac Policia Mil Estado Goias, Nucleo Pesquisa, Goiania, Go, Brazil
基金
欧洲研究理事会;
关键词
COVID-19; SARS-CoV-2; ARDS; Inflammation; Complement; Coagulation; COVID-19;
D O I
10.1093/infdis/jiaa646
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications, and mortality rate. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods. A prospective, longitudinal, single center study was performed in hospitalized patients with COVID-19. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (ax) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results. Complement factors C3a, C3c, and TCC were significantly increased in plasma of patients with COVID-19 compared with healthy controls (P < .05). These complement factors were especially elevated in intensive care unit patients during the entire disease course (P < .005 for C3a and TCC). More intense complement activation was observed in patients who died and in those with thromboembolic events. Conclusions. Patients with COVID-19 demonstrate activation of the complement system, which is related to disease severity. This pathway may be involved in the dysregulated proinflammatory response associated with increased mortality rate and thromboembolic complications. Components of the complement system might have potential as prognostic markers for disease severity and as therapeutic targets in COVID-19.
引用
收藏
页码:214 / 224
页数:11
相关论文
共 40 条
[1]   Role of C3, C5 and Anaphylatoxin Receptors in Acute Lung Injury and in Sepsis [J].
Bosmann, Markus ;
Ward, Peter A. .
CURRENT TOPICS IN INNATE IMMUNITY II, 2012, 946 :147-159
[2]   Complement in health and disease [J].
Carroll, Maria V. ;
Sim, Robert B. .
ADVANCED DRUG DELIVERY REVIEWS, 2011, 63 (12) :965-975
[3]   Activated Complement Factors as Disease Markers for Sepsis [J].
Charchaflieh, Jean ;
Rushbrook, Julie ;
Worah, Samrat ;
Zhang, Ming .
DISEASE MARKERS, 2015, 2015
[4]   The Role of Complement System in Septic Shock [J].
Charchaflieh, Jean ;
Wei, Jiandong ;
Labaze, Georges ;
Hou, Yunfang Joan ;
Babarsh, Benjamin ;
Stutz, Helen ;
Lee, Haekyung ;
Worah, Samrat ;
Zhang, Ming .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2012,
[5]   Complement-coagulation connections [J].
Conway, Edward M. .
BLOOD COAGULATION & FIBRINOLYSIS, 2018, 29 (03) :243-251
[6]   Complement activation in patients with COVID-19: A novel therapeutic target [J].
Cugno, Massimo ;
Meroni, Pier Luigi ;
Gualtierotti, Roberta ;
Griffini, Samantha ;
Grovetti, Elena ;
Torri, Adriana ;
Panigada, Mauro ;
Aliberti, Stefano ;
Blasi, Francesco ;
Tedesco, Francesco ;
Peyvandi, Flora .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2020, 146 (01) :215-+
[7]   Is COVID-19 associated thrombosis caused by overactivation of the complement cascade? A literature review [J].
Fletcher-Sandersjoo, Alexander ;
Bellander, Bo-Michael .
THROMBOSIS RESEARCH, 2020, 194 :36-41
[8]  
Foley JH, 2016, THROMB RES, V141, pS50, DOI 10.1016/S0049-3848(16)30365-6
[9]   C5A-INDUCED EXPRESSION OF P-SELECTIN IN ENDOTHELIAL-CELLS [J].
FOREMAN, KE ;
VAPORCIYAN, AA ;
BONISH, BK ;
JONES, ML ;
JOHNSON, KJ ;
GLOVSKY, MM ;
EDDY, SM ;
WARD, PA .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (03) :1147-1155
[10]  
Fu Y, 2020, HIGHLY PATHOGENIC CO, DOI [10.1101/2020.03.29.20041962, DOI 10.1101/2020.03.29.20041962]