tetano
Editor, Senior Moderator
Science
. 2024 Jan 19;383(6680):eadg7942.
doi: 10.1126/science.adg7942. Epub 2024 Jan 19. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid
Carlo Cervia-Hasler[SUP] 1 [/SUP], Sarah C Brüningk[SUP] 2 3 [/SUP], Tobias Hoch[SUP] 1 [/SUP], Bowen Fan[SUP] 2 3 [/SUP], Giulia Muzio[SUP] 2 3 [/SUP], Ryan C Thompson[SUP] 4 5 6 [/SUP], Laura Ceglarek[SUP] 1 [/SUP], Roman Meledin[SUP] 1 [/SUP], Patrick Westermann[SUP] 7 [/SUP], Marc Emmenegger[SUP] 8 [/SUP], Patrick Taeschler[SUP] 1 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Michele Pons[SUP] 1 [/SUP], Dominik Menges[SUP] 9 [/SUP], Tala Ballouz[SUP] 9 [/SUP], Sara Cervia-Hasler[SUP] 1 [/SUP], Sarah Adamo[SUP] 1 [/SUP], Miriam Merad[SUP] 4 [/SUP], Alexander W Charney[SUP] 4 5 6 [/SUP], Milo Puhan[SUP] 9 [/SUP], Petter Brodin[SUP] 10 11 [/SUP], Jakob Nilsson[SUP] 1 [/SUP], Adriano Aguzzi[SUP] 8 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Christoph B Messner[SUP] 7 [/SUP], Noam D Beckmann[SUP] 4 5 6 12 [/SUP], Karsten Borgwardt[SUP] 2 3 [/SUP], Onur Boyman[SUP] 1 13 [/SUP]
Affiliations
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.
. 2024 Jan 19;383(6680):eadg7942.
doi: 10.1126/science.adg7942. Epub 2024 Jan 19. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid
Carlo Cervia-Hasler[SUP] 1 [/SUP], Sarah C Brüningk[SUP] 2 3 [/SUP], Tobias Hoch[SUP] 1 [/SUP], Bowen Fan[SUP] 2 3 [/SUP], Giulia Muzio[SUP] 2 3 [/SUP], Ryan C Thompson[SUP] 4 5 6 [/SUP], Laura Ceglarek[SUP] 1 [/SUP], Roman Meledin[SUP] 1 [/SUP], Patrick Westermann[SUP] 7 [/SUP], Marc Emmenegger[SUP] 8 [/SUP], Patrick Taeschler[SUP] 1 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Michele Pons[SUP] 1 [/SUP], Dominik Menges[SUP] 9 [/SUP], Tala Ballouz[SUP] 9 [/SUP], Sara Cervia-Hasler[SUP] 1 [/SUP], Sarah Adamo[SUP] 1 [/SUP], Miriam Merad[SUP] 4 [/SUP], Alexander W Charney[SUP] 4 5 6 [/SUP], Milo Puhan[SUP] 9 [/SUP], Petter Brodin[SUP] 10 11 [/SUP], Jakob Nilsson[SUP] 1 [/SUP], Adriano Aguzzi[SUP] 8 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Christoph B Messner[SUP] 7 [/SUP], Noam D Beckmann[SUP] 4 5 6 12 [/SUP], Karsten Borgwardt[SUP] 2 3 [/SUP], Onur Boyman[SUP] 1 13 [/SUP]
Affiliations
- PMID: 38236961
- DOI: 10.1126/science.adg7942
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.
