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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
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Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.
Samuel B K Keat1, Priyanka Khatri2, Youssif M Ali2,3
1Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK.
Immunology
|January 25, 2026
Summary
Long COVID is linked to complement dysregulation, particularly the lectin pathway. Elevated mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes indicate lectin pathway activation in long COVID patients.
Area of Science:
- Immunology
- Complement System Biology
- Infectious Disease Pathophysiology
Background:
- Long COVID, a condition affecting SARS-CoV-2 survivors, presents diverse symptoms impacting quality of life.
- Chronic inflammation and complement system dysregulation are implicated in long COVID's etiology.
- Previous studies noted elevated complement pathway activation markers in long COVID patients.
Purpose of the Study:
- To investigate the role of the lectin complement pathway in long COVID.
- To identify potential biomarkers for long COVID using complement analytes.
- To analyze mannan-binding lectin-associated serine protease-2 (MASP-2)/C1Inh complexes in long COVID patients.
Main Methods:
- Analysis of MASP-2/C1Inh complexes in a cohort of 159 long COVID patients and 76 healthy convalescents.
- Integration of data with other predictive complement analytes.
- Application of generalized linear modeling and receiver operating characteristic (ROC) analysis.
Main Results:
- MASP-2/C1Inh complexes were significantly elevated in long COVID patients (p=0.0003).
- An optimal biomarker set (iC3b, TCC, MASP-2/C1Inh, properdin) achieved an ROC predictive power of 0.796.
- Classical complement pathway markers showed poor predictive value for long COVID.
Conclusions:
- Lectin complement pathway activation is a significant feature of long COVID.
- The lectin pathway, upstream of alternative and terminal pathways, is a potential therapeutic target.
- A combination of complement markers can effectively predict long COVID status.
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