Complement activation in patients with post-acute sequelae after SARS-CoV-2 infection

Front Immunol. 2026 May 13:17:1779393. doi: 10.3389/fimmu.2026.1779393. eCollection 2026.

Abstract

Introduction: Post-acute sequelae of SARS-CoV-2 (PASC) may develop after SARS-CoV-2 infection and cause a wide range of symptoms that can persist for years. Several pathophysiological mechanisms have been proposed, including dysregulation of the complement system.

Methods: In this study, we analysed markers of complement activation in a cohort of patients with PASC, up to 33 months after the initial infection. We measured the complement activation markers C3bc, C3bBbP and TCC in 38 PASC patients with an initial mild COVID-19 infection, 10 PASC patients with an initial severe COVID-19 infection and 80 control subjects who had recovered completely after a COVID-19 infection.

Results: Although the patients with an acute mild SARS-CoV-2 infection had a trend towards more severe PASC, we could not find any significant differences in complement activation markers between these patients and controls.

Conclusion: We could not find convincing evidence of activation of the complement system in PASC patients.

Keywords: COVID-19; PACS; PASC; SARS-CoV-2; complement activation; long COVID; post COVID syndrome.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Complement Activation* / immunology
  • Complement C3b / immunology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Post-Acute COVID-19 Syndrome* / immunology
  • SARS-CoV-2* / immunology

Substances

  • Biomarkers
  • Complement C3b