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Association of Complement C3 with Clinical Deterioration Among Hospitalized Patients with COVID-19
Hongbo Jiang1, Qiaosen Chen1, Shaoping Zheng2
1Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
Insights
Low complement C3 levels in COVID-19 patients indicate a higher risk of clinical worsening. This finding may help identify patients who could benefit from complement inhibition therapies.
Area of Science:
- Immunology
- Infectious Diseases
- Critical Care Medicine
Background:
- The complement system's role in COVID-19 pathogenesis is debated.
- Understanding complement C3 levels may clarify disease progression.
Purpose of the Study:
- To investigate the association between serum complement C3 levels and clinical worsening or death in hospitalized COVID-19 patients.
- To evaluate C3 as a potential biomarker for COVID-19 severity.
Main Methods:
- Retrospective analysis of 216 hospitalized COVID-19 patients.
- Measurement of serum C3 levels within 24 hours of admission.
- Inverse Probability of Treatment Weighting (IPTW) analysis to control for confounders.
Main Results:
- Lower C3 levels (<0.79 g/L) were associated with a significantly higher risk of clinical worsening (weighted HR, 4.61).
- Sensitivity analyses confirmed the robustness of this association.
- No significant association was found between C3 levels and all-cause mortality.
Conclusions:
- Low serum C3 levels are linked to increased clinical worsening risk in COVID-19 inpatients.
- Serum C3 may serve as a predictive biomarker for COVID-19 severity.
- These findings suggest potential benefits of complement inhibition for specific patient groups.
Background:
The role of the complement system in coronavirus disease 2019 (COVID-19) remains controversial. This study aimed to evaluate the relationship between serum complement C3 levels, clinical worsening, and risk of death in hospitalized patients with COVID-19.
Methods:
Data were collected from 216 adults with COVID-19 admitted to a designated clinical center in Wuhan Union Hospital (China) between February 13, 2020, and February 29, 2020. Their complement C3 levels were measured within 24 h of admission. The primary outcome was a clinical worsening of 2 points on a 6-point ordinal scale. The secondary outcome was all-causes of death. Inverse probability of treatment weighting (IPTW) analysis was conducted to adjust for the baseline confounders.
Results:
The median value of C3 was 0.89 (interquartile range, 0.78-1.01) g/L. Clinical worsening occurred in 12.3% (7/57) and 2.5% (4/159) of patients with baseline C3 levels < and ≥0.79 g/L, respectively (hazard ratio [HR], 5.22; 95% confidence interval [CI], 1.53-17.86). After IPTW adjustment, the risk for clinical worsening was 4-fold greater (weighted HR, 4.61; 95% CI, 1.16-18.4) in patients with C3 levels less than 0.79 g/L comparatively. The sensitivity analyses revealed the robustness of the results. No significant associations between C3 levels and death were observed on unadjusted (HR, 2.92; 95% CI, 0.73-11.69) and IPTW analyses (weighted HR, 3.78; 95% CI, 0.84-17.04).
Conclusion:
Low complement C3 levels are associated with a higher risk for clinical worsening among inpatients with COVID-19. The serum C3 levels may contribute to the identification of patient populations that could benefit from therapeutic complement inhibition.
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