SARS-CoV-2 Infection and C1-Esterase Inhibitor: Camouflage Pattern
and New Perspective

Hayder   M.   Al-kuraishy; Ali   I.   Al-Gareeb; Naif   A.   Jalal; Saeed   M   Kabrah; Athanasios      Alexiou; Gaber   El-Saber   Batiha
Abstract

In Covid-19, the pathological effect of SARS-CoV-2 infection is arbitrated through direct viral toxicity, unusual immune response, endothelial dysfunction, deregulated renin-angiotensin system [RAS], and thrombo-inflammation, leading to acute lung injury (ALI), with a succession of acute respiratory distress syndrome (ARDS) in critical conditions. C1 esterase inhibitor (C1INH) is a protease inhibitor that inhibits the spontaneous activation of complement and contact systems and kinin pathway, clotting, and fibrinolytic systems. Therefore, targeting the complement system through activation of C1INH might be a novel therapeutic modality in the treatment of Covid-19. Therefore, this study aims to illustrate the potential nexus between C1INH and the pathophysiology of SARS-CoV-2 infection. C1INH is highly dysregulated in Covid-19 due to inflammatory and coagulation disorders. C1INH is up-regulated in Covid-19 and sepsis as an acute phase response, but this increase is insufficient to block the activated complement system. In addition, the C1INH serum level predicts the development of ARDS in Covid-19 patients, as its up-regulation is associated with the development of cytokine storm. In Covid-19, C1INH might be inhibited or dysregulated by SARS-CoV-2, leading to propagation of complement system activation with subsequent uncontrolled immunological stimulation due to activation of bradykinin and FXII with sequential activation of coagulation cascades and polymerization of fibrin. Thus, suppression of C1INH by SARS-CoV-2 infection leads to thrombosis and excessive inflammation due to uncontrolled activation of complements and contact systems.
Keywords: Covid-19, SARS-CoV-2, C1-esterase inhibitor, complement system, acute lung injury (ALI), acute respiratory distress syndrome (ARDS).
Graphical Abstract

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Cite As
Current Protein & Peptide Science

SARS-CoV-2 Infection and C1-Esterase Inhibitor: Camouflage Pattern and New Perspective

Abstract

Graphical Abstract
