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

Cell Rep Med. 2022 Jun 21;3(6):100663. doi: 10.1016/j.xcrm.2022.100663.

Abstract

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.

Keywords: COVID-19; IL-1β; IL-6; PASC; SARS-CoV-2; TNF; cytokine; long covid; macrophage; post-acute sequelae of COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / complications
  • COVID-19* / immunology
  • COVID-19* / pathology
  • Cohort Studies
  • Cytokines* / immunology
  • Disease Progression
  • Humans
  • Immunologic Tests
  • Interleukin-1beta / immunology
  • Interleukin-6 / immunology
  • Post-Acute COVID-19 Syndrome
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha