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Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.
Cervia-Hasler, Carlo; Brüningk, Sarah C; Hoch, Tobias; Fan, Bowen; Muzio, Giulia; Thompson, Ryan C; Ceglarek, Laura; Meledin, Roman; Westermann, Patrick; Emmenegger, Marc; Taeschler, Patrick; Zurbuchen, Yves; Pons, Michele; Menges, Dominik; Ballouz, Tala; Cervia-Hasler, Sara; Adamo, Sarah; Merad, Miriam; Charney, Alexander W; Puhan, Milo; Brodin, Petter; Nilsson, Jakob; Aguzzi, Adriano; Raeber, Miro E; Messner, Christoph B; Beckmann, Noam D; Borgwardt, Karsten; Boyman, Onur.
Afiliación
  • Cervia-Hasler C; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Brüningk SC; Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
  • Hoch T; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
  • Fan B; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Muzio G; Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
  • Thompson RC; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
  • Ceglarek L; Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland.
  • Meledin R; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
  • Westermann P; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Emmenegger M; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Taeschler P; Mount Sinai Clinical Intelligence Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Zurbuchen Y; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Pons M; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Menges D; Precision Proteomics Center, Swiss Institute of Allergy and Asthma Research, University of Zurich, 7265 Davos, Switzerland.
  • Ballouz T; Institute of Neuropathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Cervia-Hasler S; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Adamo S; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Merad M; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Charney AW; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, 8001 Zurich, Switzerland.
  • Puhan M; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, 8001 Zurich, Switzerland.
  • Brodin P; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Nilsson J; Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
  • Aguzzi A; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Raeber ME; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Messner CB; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Beckmann ND; Mount Sinai Clinical Intelligence Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Borgwardt K; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, 8001 Zurich, Switzerland.
  • Boyman O; Unit for Clinical Pediatrics, Department of Women's and Children's Health, Karolinska Institute, 17165 Solna, Sweden.
Science ; 383(6680): eadg7942, 2024 01 19.
Article en En | MEDLINE | ID: mdl-38236961
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Sistema Complemento / Activación de Complemento / Proteoma / Tromboinflamación / Síndrome Post Agudo de COVID-19 Tipo de estudio: Diagnostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Sistema Complemento / Activación de Complemento / Proteoma / Tromboinflamación / Síndrome Post Agudo de COVID-19 Tipo de estudio: Diagnostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos