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

Abstract

Post-acute sequelae of COVID-19 (PASC) emerge as a global problem with unknown molecular drivers. In a digital epidemiology approach, we rapidly recruited 8,077 individuals out of 129,733 households in Halle (Saale) to the cohort study for digital health research in Germany (DigiHero). These responded to a basic questionnaire followed by a PASC-focused survey and blood sampling in case of prior positive SARS-CoV-2 testing in their household. The presented analysis is based on the first 318 DigiHero participants, the majority thereof after mild infections. PASC were reported in 67.8% of cases, consisted predominantly in fatigue, dyspnea and concentration deficit, persisted in 60% over the follow-up period of on average eight months and their resolution was unaffected by post-infection vaccination. PASC was not associated with post-COVID-19 autoantibodies, but with elevated levels of IL-1ß, IL-6 and TNF-α. Blood profiling and single-cell data from validation cohorts with early infection suggested the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop. Our data indicate a long-lasting cytokine triad -potentially underlying PASC symptoms - to be driven by macrophage primed during infection. We demonstrate how the combination of digital epidemiology with selective biobanking can rapidly generate hints towards disease mechanisms.

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• Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC) · 2023
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• ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature · 2023
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• Prevalence and clinical presentation of long COVID in children: a systematic review · 2022
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