Measuring complement regulators in SARS-CoV-2 plasma

Abstract

Abstract Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, has created global public health concern. One ongoing challenge of SARS-CoV-2 infection is the unpredictable and variable clinical spectrum of COVID-19 patients. SARS-CoV-2 induces overabundant immune response that causes complications such as severe respiratory distress syndrome, sepsis, multiorgan dysfunction and possible death. Several studies have reported that COVID-19 immunopathogenesis might be associated with overactivation of complements, which mediates hyperinflammatory status. The aim of this paper is to investigate whether expression of complement regulators is correlated with COVID- 19 disease progression. Method: We performed liquid-chromatography-selected reaction monitoring mass spectrometry (LC-SRM-MS) to measure circulating concentration of complement regulatory proteins FH, FHL-1, and FHR1 to FHR5 in 112 COVID-19 patients divided into 5 groups (asymptomatic and symptomatic screening groups, and mild, moderate, and severe COVID-19 patients). We also had 30 healthy control and 46 non-COVID-19 patients. Result: This paper showed that the level of FHL-1 and FHR proteins but not the level of FH was significantly higher in severe COVID-19 patients versus the controls. Furthermore, to the best of our knowledge, we are the first to report a significant elevation of circulating levels of FHL-1, FHR1, FHR2, FHR3 and FHR5 between the symptomatic screening group (B) compared to severe COVID-19 patients. We are also the first to suggest that FHR5 might be a robust candidate biomarker for predicting patients who might develop severe SARS-CoV-2 infection. FHR5 showed the highest diagnostic performance on an ROC curve with AUC = 0.9344, detecting a significant change among most groups. Combining these results with age, gender, ethnicity and comorbidity status could provide more predictive power. Conclusion: The findings of this paper report that the expression of FHL-1 and FHR is highly associated with the progression of COVID-19.