C3a and C5b-9 levels differentially predict COVID-19 severity and mortality.

Abstract

Introduction: SARS-COV-2 infection may result in pneumonia leading to ARDS and ICU treatment. Activation of the complement system was verified in COVID-19 patients as a driving factor of thromboinflammation contributing to disease progression.

Aim: To investigate C3a and C5b-9 levels as markers of COVID-19 severity and outcome.

Methods: 79 patients with a positive polymerase chain reaction (PCR) test for SARS-COV-2 were recruited; 38 severe and 42 critical. Serum samples were collected on admission and analysed for C3a and C5b-9 levels by ELISA methodology. Patients were grouped into severe vs critical, non-intubated vs intubated and survivors vs non-survivors for comparisons. Statistical analysis by Mann-Whitney for non-parametric analysis and receiving operating curve (ROC) analysis was performed in GraphPad Prism.

Results: A statistically significant increase for C3a and C5b-9 levels was observed between: a) severe vs critical (p<0.001 and p<0.0001), b) non-intubated vs intubated (p<0.001 and p<0.05) survivors vs non-survivors (p<0.001 and p<0.01). ROC analysis for ICU admission revealed a higher AUC for C5b-9 (0.771, p<0.001) compared to C3a (AUC= 0.686, p<0.01). A higher AUC was observed for C3a when analysis was performed for intubation need (AUC=0.746, p<0.001) or mortality (AUC=0.758, p<0.0001) compared to C5b-9 (intubation need AUC=0.663, p<0.05 and mortality AUC=0.637, p NS). Combining C3a and C5b9 revealed a powerful prediction tool for ICU admission (AUC=0.773, p<0.0001), intubation (AUC=0.756, p<0.0001) and mortality (AUC=0.753, p<0.001).

Conclusion: C3a and C5b-9 may serve as prognostic tools either separately or in combination for the progression and outcome of COVID-19.