Evaluation of Complement Pathway Activation Markers in COVID-19 Patients

Abstract

Background: Complement activation has been implicated in pathogenesis of SARS-CoV2 and needs further evaluation as its unrestricted activation leads to damaging effects for the host. Regulatory mechanism plays a key role in complement activation during the infection and should be investigated. Screening complement activation by SARS-CoV2 may help to explore the possible complement fragment as an indicator of activation thus helping the diagnosis of COVID19.Methods: Plasma samples of consented participants (n=40 cases; n=40 controls) were evaluated for C4b, C5b-9, IL-6, D-dimer and C1-Inhibitor by ELISA Kits. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA).Findings: Significantly increased levels of C4b, D- dimer, IL6, along with decreased levels of C1 INH were found in cases (mean age=54.25) than in controls (mean age=27.25). However, C5b-9 levels were not significantly raised in cases. The significantly higher levels of C4b in cases with a cut-off value of ≥121.5ng/ml with optimum sensitivity and specificity 77.5% and 85% respectively, suggest that C4b may be considered as an adjunct diagnostic marker in diagnosis of SARS-CoV2 infection. False negative results, by any diagnostic test can be more consequential, as it sets the infected persons free to infect others. In such cases, C4b evaluation may be of great help in detecting infection in cases which have been falsely labelled as negative and can be instrumental in limiting the spread of infection.Interpretation: Our study proposes C4b as an important supportive diagnostic marker to eliminate false negative cases.Funding Statement: All India Institute of Medical Sciences Patna, award no. I-6/529.Declaration of Interests: Authors do not have any conflict of interest.Ethics Approval Statement: The study was approved by IEC of AIIMS Patna (Ref. No. AIIMS/Pat/IEC/2020/529). Prior consent from patients and normal healthy individuals for controls was obtained.