Persistent complement dysregulation with signs of thromboinflammation in active Long Covid-Reference-Cited by-同舟云学术

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Published:2024-01-19 Issue:6680 Volume:383 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Cervia-Hasler Carlo¹^ORCID,Brüningk Sarah C.²³^ORCID,Hoch Tobias¹^ORCID,Fan Bowen²³,Muzio Giulia²³^ORCID,Thompson Ryan C.⁴⁵⁶^ORCID,Ceglarek Laura¹^ORCID,Meledin Roman¹^ORCID,Westermann Patrick⁷^ORCID,Emmenegger Marc⁸^ORCID,Taeschler Patrick¹^ORCID,Zurbuchen Yves¹^ORCID,Pons Michele¹^ORCID,Menges Dominik⁹^ORCID,Ballouz Tala⁹^ORCID,Cervia-Hasler Sara¹^ORCID,Adamo Sarah¹^ORCID,Merad Miriam⁴^ORCID,Charney Alexander W.⁴⁵⁶^ORCID,Puhan Milo⁹,Brodin Petter¹⁰¹¹^ORCID,Nilsson Jakob¹^ORCID,Aguzzi Adriano⁸^ORCID,Raeber Miro E.¹^ORCID,Messner Christoph B.⁷^ORCID,Beckmann Noam D.⁴⁵⁶¹²^ORCID,Borgwardt Karsten²³^ORCID,Boyman Onur¹¹³^ORCID

Affiliation:

1. Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.

2. Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.

3. Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.

4. Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

5. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

6. Mount Sinai Clinical Intelligence Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

7. Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research, University of Zurich, 7265 Davos, Switzerland.

8. Institute of Neuropathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.

9. Epidemiology, Biostatistics and Prevention Institute, University of Zurich, 8001 Zurich, Switzerland.

10. Unit for Clinical Pediatrics, Department of Women’s and Children’s Health, Karolinska Institute, 17165 Solna, Sweden.

11. Department of Immunology and Inflammation, Imperial College London, London W12 0NN, UK.

12. Division of Data Driven and Digital Medicine (D3M), Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

13. Faculty of Medicine and Faculty of Science, University of Zurich, 8006 Zurich, Switzerland.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adg7942

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