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Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID

Kirsten Baillie1, Helen E Davies2, Samuel B K Keat1

  • 1Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Heath Park, Cardiff CF14 4XN, UK.

Med (New York, N.Y.)
|February 15, 2024
PubMed

Insights

Long COVID patients show elevated complement activation markers, suggesting a role for the complement system in the condition. These biomarkers could aid in diagnosing and treating long COVID with existing complement inhibitors.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Systems Biology

Background:

  • Long COVID presents diverse ongoing symptoms post-SARS-CoV-2 infection, with unclear biological underpinnings.
  • Complement system dysregulation is known in acute COVID-19 but unexamined in long COVID.
  • Understanding long COVID mechanisms is crucial for diagnosis and treatment.

Purpose of the Study:

  • Investigate the role of complement system activation and regulation in long COVID.
  • Identify potential biomarkers for long COVID diagnosis.
  • Explore therapeutic targets for long COVID.

Main Methods:

  • Quantified complement proteins and activation/regulation markers in plasma from long COVID patients and healthy convalescents.
  • Utilized age, ethnicity, sex, infection, and vaccine matching for sample groups.
  • Employed generalized linear modeling for biomarker analysis.

Main Results:

  • Significantly elevated classical, alternative, and terminal complement pathway activation markers in long COVID patients.
  • A combination of four markers (iC3b, TCC, Ba, C5a) demonstrated a predictive power of 0.785 for long COVID.
  • Other complement proteins and regulators also showed quantitative differences between groups.

Conclusions:

  • Complement biomarkers show potential for facilitating long COVID diagnosis.
  • Complement activation inhibitors may offer a therapeutic strategy for long COVID.
  • This study highlights the complement system's involvement in long COVID pathogenesis.
Abstract

Keywords:
Translation to patientsbiomarkers of diseasecomplement systemlong COVID

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