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Classic pathway persistent complement activation is associated with specific symptoms in individuals with

César Fernández-de-Las-Peñas1, Maria Ruiz-Ruigómez2, Laura Esparcia-Pinedo3

  • 1Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos (URJC), Madrid, Spain; Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases
|August 30, 2025
PubMed

Insights

This study found no overall complement activation in COVID-19 survivors with post-COVID-19 condition. However, specific symptoms like fatigue and dyspnea were linked to lower levels of certain complement proteins.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Clinical Medicine

Background:

  • The complement system is a key immune component, but its role in post-COVID-19 condition remains unclear.
  • Investigating complement activation may offer insights into the pathophysiology of long-term COVID-19 symptoms.

Purpose of the Study:

  • To investigate long-lasting complement hyperactivation in COVID-19 survivors with and without post-COVID-19 condition.
  • To determine if complement pathway activation is associated with the presence of specific post-COVID-19 symptoms.

Main Methods:

  • A case-control study (2:1 design) compared COVID-19 survivors with and without post-COVID-19 condition.
  • Blood samples were analyzed for classical complement pathway proteins (C3, C4, C5, C7) and total hemolytic complement (CH50) activity.
  • Post-COVID-19 condition was defined by self-reported symptoms including fatigue, arthralgia, myalgia, memory problems, headache, or palpitations.

Main Results:

  • No significant differences in overall complement protein levels or CH50 activity were found between groups.
  • Patients with post-COVID fatigue showed lower C3 levels compared to those without fatigue.
  • Survivors with post-COVID dyspnea exhibited lower levels of C3, C5, and C7 proteins.

Conclusions:

  • This study did not find evidence of overall classical complement pathway activation in COVID-19 survivors with post-COVID-19 condition up to two years post-infection.
  • Specific complement proteins were associated with particular post-COVID-19 symptoms, suggesting a nuanced role in the condition.
Abstract

Keywords:
ComplementDyspneaFatigueLong-COVIDPlasmapost–COVID-19

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