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Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19
Lorena Viana de Andrade1, Beatriz Vasconcelos2, Ricardo Khouri2
1Postgraduate Program in Biosciences, Federal University of the São Francisco Valley, Petrolina, Brazil.
Insights
Elevated complement proteins like C2, C5a, factor B, and factor D are linked to severe COVID-19 complications. These findings suggest complement system molecules could be biomarkers for COVID-19 progression.
Area of Science:
- Immunology
- Virology
- Critical Care Medicine
Background:
- The complement system is crucial for pathogen defense but can cause tissue damage in severe COVID-19.
- Hyperactivation of complement may dysregulate coagulation, leading to vascular damage in severe COVID-19.
- Limited data exists on complement protein levels and COVID-19 clinical outcomes.
Purpose of the Study:
- To investigate the association between plasma complement protein levels and clinical evolution in hospitalized COVID-19 patients.
- To explore the relationship between complement proteins, coagulation, and kidney function in COVID-19.
Main Methods:
- Plasma samples from 267 hospitalized COVID-19 patients were analyzed for complement proteins (C2, C3, C4, C5, C5a, MBL, C1q, factors B, D, H, I) using Luminex.
- Patients were categorized by severity and followed for complications, including ICU admission, ventilation, sepsis, cardiorespiratory arrest, and acute kidney failure.
- Multivariate logistic regression adjusted for confounding factors.
Main Results:
- Higher plasma levels of C2, C5a, factor B, and factor D were observed in patients with critical illness indicators (ICU admission, ventilation, sepsis, cardiorespiratory arrest, acute kidney failure).
- Lower C4b levels were associated with the development of complications.
- Complement protein levels showed significant associations with coagulation and kidney function parameters.
Conclusions:
- The complement system is significantly associated with COVID-19 complications.
- Complement protein levels correlate with laboratory markers of coagulation and kidney function.
- These complement molecules represent potential biomarkers or therapeutic targets for managing COVID-19 progression.
Background:
The complement system is an important defense mechanism against pathogens, including viruses. In COVID-19, evidence suggests that hyperactivation of the complement system can lead to tissue damage and provoke dysregulation of the coagulation cascade, resulting in vascular damage observed in severe COVID-19. There is still little evidence regarding the role of plasma levels of these molecules in the clinical evolution of hospitalized patients with COVID-19.
Methods:
The study included individuals 18 years of age or older with confirmed diagnosis of COVID-19, admitted to two referral hospitals in the Northeast Region of Brazil between August 2020 and July 2021. Plasma samples were collected within 24 hours of hospital admission. Patients were followed up until discharge, and complications during hospitalization were duly recorded. Plasma levels of the following complement proteins were determined by Luminex: C2, C3, C3b/iC3b, C4, C4b, C5, C5a, MBL, C1q, factor I, factor D, factor B, and factor H. A multivariate logistic regression analysis was used to correct the results according to possible confounding factors.
Results:
The study included 267 patients (134 critical and 133 severe), with mean ages of 54 and 52 years, respectively. Plasma levels of C2, C5a, factor B, and factor D were significantly higher in patients who required intensive care unit admission, required ventilatory support, developed sepsis, developed cardiorespiratory arrest, or developed acute kidney failure. On the other hand, C4b level was lower in patients who developed complications. Complement proteins were significantly associated with laboratory parameters related to coagulation and kidney function.
Conclusion:
These findings show that the complement system is associated with COVID-19 complications and laboratory parameters of coagulation and kidney function. These results suggest that these molecules may be potential biomarkers or therapeutic targets in the clinical progression of COVID-19.
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