Persistent complement dysregulation with signs of thromboinflammation in active Long Covid

• 成果类型: Article
• 署名作者: Cervia-Hasler, Carlo; Brueningk, 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
• 署名单位: University of Zurich; University Zurich Hospital; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Institute of Bioinformatics; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Zurich; Swiss Institute of Allergy & Asthma Research; University of Zurich; University Zurich Hospital; University of Zurich; Swiss School of Public Health (SSPH+); Karolinska Institutet; Imperial College London; Icahn School of Medicine at Mount Sinai; University of Zurich; University of Geneva; University of Zurich
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12058
• DOI: 10.1126/science.adg7942
• 发表日期: 2024-01-19
• 关键词: humoral innate immunity; endothelial-cells; activation; c7; modulation; sars-cov-2; disease

摘要

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.