Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Carlo Cervia-Hasler¹, Sarah C Brüningk^{2

3}, Tobias Hoch¹, Bowen Fan^{2

3}, Giulia Muzio^{2

3}, Ryan C Thompson^{4

5

6}, Laura Ceglarek¹, Roman Meledin¹, Patrick Westermann⁷, Marc Emmenegger⁸, Patrick Taeschler¹, Yves Zurbuchen¹, Michele Pons¹, Dominik Menges⁹, Tala Ballouz⁹, Sara Cervia-Hasler¹, Sarah Adamo¹, Miriam Merad⁴, Alexander W Charney^{4

5

6}, Milo Puhan⁹, Petter Brodin^{10

11}, Jakob Nilsson¹, Adriano Aguzzi⁸, Miro E Raeber¹, Christoph B Messner⁷, Noam D Beckmann^{4

5

6

12}, Karsten Borgwardt^{2

3}, Onur Boyman^{1

13}

Affiliations

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.

PMID: 38236961
DOI: 10.1126/science.adg7942

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Carlo Cervia-Hasler et al. Science. 2024.

. 2024 Jan 19;383(6680):eadg7942.

doi: 10.1126/science.adg7942. Epub 2024 Jan 19.

Authors

Affiliations

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.

PMID: 38236961
DOI: 10.1126/science.adg7942

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.

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Comment in

Mögliche Biomarker für Long Covid entdeckt.
Berlit P. Berlit P. MMW Fortschr Med. 2024 May;166(9):24. doi: 10.1007/s15006-024-3936-x. MMW Fortschr Med. 2024. PMID: 38755365 German. No abstract available.
Abnormal complement activation is a sign of long COVID.
Forte E. Forte E. Nat Cardiovasc Res. 2024 Feb;3(2):95. doi: 10.1038/s44161-024-00434-y. Nat Cardiovasc Res. 2024. PMID: 39196199 No abstract available.

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Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

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Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

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Abstract

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