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The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

2022; Elsevier BV; Volume: 3; Issue: 6 Linguagem: Inglês

10.1016/j.xcrm.2022.100663

2666-3791

Christoph Schultheiß, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Svenja-Sibylla Henkes, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Höll, Michael Gekle, Rafael Mikolajczyk, Mascha Binder,

COVID-19 Clinical Research Studies

Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.