Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Cervia-Hasler C, BrĂ¼ningk 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

Science 383 (6680) eadg7942 [2024-01-19; online 2024-01-19]

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.

Category: Post-COVID

Funder: H2020

Type: Journal article

PubMed 38236961

DOI 10.1126/science.adg7942

Crossref 10.1126/science.adg7942


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