Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

Carlo Cervia(University of Zurich), Sarah C. Brüningk(SIB Swiss Institute of Bioinformatics), Tobias Hoch(University of Zurich), Bowen Fan(SIB Swiss Institute of Bioinformatics), Giulia Muzio(SIB Swiss Institute of Bioinformatics), Ryan C. Thompson(Icahn School of Medicine at Mount Sinai), Laura Ceglarek(University of Zurich), Roman Meledin(University of Zurich), Patrick Westermann(Swiss Finance Institute), Marc Emmenegger(University Hospital of Zurich), Patrick Taeschler(University of Zurich), Yves Zurbuchen(University of Zurich), Michele Pons(University of Zurich), Dominik Menges(University of Zurich), Tala Ballouz(University of Zurich), Sara Hasler(University of Zurich), Sarah Adamo(University of Zurich), Miriam Mérad(Icahn School of Medicine at Mount Sinai), Alexander W. Charney(Icahn School of Medicine at Mount Sinai), Milo A. Puhan(University of Zurich), Petter Brodin(Karolinska Institutet), Jakob Nilsson(University of Zurich), Adriano Aguzzi(University Hospital of Zurich), Miro E. Raeber(University of Zurich), Christoph B. Messner(Swiss Finance Institute), Noam D. Beckmann(Icahn School of Medicine at Mount Sinai), Karsten Borgwardt(SIB Swiss Institute of Bioinformatics), Onur Boyman(University of Zurich)
Science
January 18, 2024
10.1126/science.adg7942
Cited by 379Open Access
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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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