Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

被引：198

作者：

Cervia-Hasler, Carlo ^{[1
]}

Brueningk, Sarah C. ^{[2
,3
]}

Hoch, Tobias ^{[1
]}

Fan, Bowen ^{[2
,3
]}

Muzio, Giulia ^{[2
,3
]}

Thompson, Ryan C. ^{[4
,5
,6
]}

Ceglarek, Laura ^{[1
]}

Meledin, Roman ^{[1
]}

Westermann, Patrick ^{[7
]}

Emmenegger, Marc ^{[8
]}

Taeschler, Patrick ^{[1
]}

Zurbuchen, Yves ^{[1
]}

Pons, Michele ^{[1
]}

Menges, Dominik ^{[9
]}

Ballouz, Tala ^{[9
]}

Cervia-Hasler, Sara ^{[1
]}

Adamo, Sarah ^{[1
]}

Merad, Miriam ^{[4
]}

Charney, Alexander W. ^{[4
,5
,6
]}

Puhan, Milo ^{[9
]}

Brodin, Petter ^{[10
,11
]}

Nilsson, Jakob ^{[1
]}

Aguzzi, Adriano ^{[8
]}

Raeber, Miro E. ^{[1
]}

Messner, Christoph B. ^{[7
]}

Beckmann, Noam D. ^{[4
,5
,6
,12
]}

Borgwardt, Karsten ^{[2
,3
]}

Boyman, Onur ^{[1
,13
,14
]}

机构：

[1] Univ Zurich, Dept Immunol, Univ Zurich Hosp, CH-8091 Zurich, Switzerland

[2] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland

[3] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[4] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Mt Sinai Clin Intelligence Ctr, New York, NY 10029 USA

[7] Univ Zurich, Swiss Inst Allergy & Asthma Res, Precis Prote Ctr, CH-7265 Davos, Switzerland

[8] Univ Zurich, Univ Hosp Zurich, Inst Neuropathol, CH-8091 Zurich, Switzerland

[9] Univ Zurich, Epidemiol Biostat & Prevent Inst, CH-8001 Zurich, Switzerland

[10] Karolinska Inst, Dept Womens & Childrens Hlth, Unit Clin Pediat, S-17165 Solna, Sweden

[11] Imperial Coll London, Dept Immunol & Inflammat, London W12 0NN, England

[12] Icahn Sch Med Mt Sinai, Dept Med, Div Data Driven & Digital Med D3M, New York, NY 10029 USA

[13] Univ Zurich, Fac Med, CH-8006 Zurich, Switzerland

[14] Univ Zurich, Fac Sci, CH-8006 Zurich, Switzerland

来源：

SCIENCE | 2024年 / 383卷 / 6680期

基金：

瑞士国家科学基金会;

关键词：

HUMORAL INNATE IMMUNITY; ENDOTHELIAL-CELLS; ACTIVATION; C7; MODULATION; SARS-COV-2; DISEASE;

D O I：

10.1126/science.adg7942

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

引用

页码：1 / 18

页数：19

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