Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Carlo Cervia-Hasler; Sarah C. Brüningk; Tobias Hoch; Bowen Fan; Giulia Muzio; Ryan C. Thompson; Laura Ceglarek; Roman Meledin; Patrick Westermann; Marc Emmenegger; Patrick Taeschler; Yves Zurbuchen; Michele Pons; Dominik Menges; Tala Ballouz; Sara Cervia-Hasler; Sarah Adamo; Miriam Merad; Alexander W. Charney; Milo Puhan; Petter Brodin; Jakob Nilsson; Adriano Aguzzi; Miro E. Raeber; Christoph B. Messner; Noam D. Beckmann; Karsten Borgwardt; Onur Boyman

doi:10.1126/science.adg7942

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Carlo Cervia-Hasler, Sarah C. Brüningk, Tobias Hoch, Bowen Fan, Giulia Muzio, Ryan C. Thompson, Laura Ceglarek, Roman Meledin, Patrick Westermann, Marc Emmenegger, Patrick Taeschler, Yves Zurbuchen, Michele Pons, Dominik Menges, Tala Ballouz, Sara Cervia-Hasler, Sarah Adamo, Miriam Merad, Alexander W. Charney, Milo PuhanPetter Brodin, Jakob Nilsson, Adriano Aguzzi, Miro E. Raeber, Christoph B. Messner, Noam D. Beckmann, Karsten Borgwardt, Onur Boyman

Research output: Contribution to journal › Article › peer-review

238 Scopus citations

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.

Original language	English
Pages (from-to)	1-18
Number of pages	18
Journal	Science
Volume	383
Issue number	6680
DOIs	https://doi.org/10.1126/science.adg7942
State	Published - Jan 2024

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Cervia-Hasler, C., Brüningk, S. C., Hoch, T., Fan, B., Muzio, G., Thompson, R. C., Ceglarek, L., Meledin, R., Westermann, P., Emmenegger, M., Taeschler, P., Zurbuchen, Y., Pons, M., Menges, D., Ballouz, T., Cervia-Hasler, S., Adamo, S., Merad, M., Charney, A. W., ... Boyman, O. (2024). Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science, 383(6680), 1-18. https://doi.org/10.1126/science.adg7942

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title = "Persistent complement dysregulation with signs of thromboinflammation in active Long Covid",

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.",

author = "Carlo Cervia-Hasler and Br{\"u}ningk, \{Sarah C.\} and Tobias Hoch and Bowen Fan and Giulia Muzio and Thompson, \{Ryan C.\} and Laura Ceglarek and Roman Meledin and Patrick Westermann and Marc Emmenegger and Patrick Taeschler and Yves Zurbuchen and Michele Pons and Dominik Menges and Tala Ballouz and Sara Cervia-Hasler and Sarah Adamo and Miriam Merad and Charney, \{Alexander W.\} and Milo Puhan and Petter Brodin and Jakob Nilsson and Adriano Aguzzi and Raeber, \{Miro E.\} and Messner, \{Christoph B.\} and Beckmann, \{Noam D.\} and Karsten Borgwardt and Onur Boyman",

year = "2024",

month = jan,

doi = "10.1126/science.adg7942",

language = "English",

volume = "383",

pages = "1--18",

journal = "Science",

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publisher = "American Association for the Advancement of Science",

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Cervia-Hasler, C, Brüningk, SC, Hoch, T, Fan, B, Muzio, G, Thompson, RC, Ceglarek, L, Meledin, R, Westermann, P, Emmenegger, M, Taeschler, P, Zurbuchen, Y, Pons, M, Menges, D, Ballouz, T, Cervia-Hasler, S, Adamo, S, Merad, M, Charney, AW, Puhan, M, Brodin, P, Nilsson, J, Aguzzi, A, Raeber, ME, Messner, CB, Beckmann, ND, Borgwardt, K & Boyman, O 2024, 'Persistent complement dysregulation with signs of thromboinflammation in active Long Covid', Science, vol. 383, no. 6680, pp. 1-18. https://doi.org/10.1126/science.adg7942

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AU - Cervia-Hasler, Carlo

AU - Brüningk, Sarah C.

AU - Hoch, Tobias

AU - Fan, Bowen

AU - Muzio, Giulia

AU - Thompson, Ryan C.

AU - Ceglarek, Laura

AU - Meledin, Roman

AU - Westermann, Patrick

AU - Emmenegger, Marc

AU - Taeschler, Patrick

AU - Zurbuchen, Yves

AU - Pons, Michele

AU - Menges, Dominik

AU - Ballouz, Tala

AU - Cervia-Hasler, Sara

AU - Adamo, Sarah

AU - Merad, Miriam

AU - Charney, Alexander W.

AU - Puhan, Milo

AU - Brodin, Petter

AU - Nilsson, Jakob

AU - Aguzzi, Adriano

AU - Raeber, Miro E.

AU - Messner, Christoph B.

AU - Beckmann, Noam D.

AU - Borgwardt, Karsten

AU - Boyman, Onur

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85182836897

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DO - 10.1126/science.adg7942

M3 - Article

C2 - 38236961

AN - SCOPUS:85182836897

SN - 0036-8075

VL - 383

SP - 1

EP - 18

JO - Science

JF - Science

IS - 6680

ER -

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Abstract

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