Complement contributions to COVID-19. Issue 5 (11th September 2022)

• Record Type: Journal Article
• Authors: Conway, Edward M.; Pryzdial, Edward L.G.
• Is Part Of: Current opinion in hematology. Volume 29:Issue 5(2022)
• Page Start: 259
• Page End: 265
• Publication Date: 2022-09-11
• Subjects: complement system -- COVID-19 -- endothelium -- innate immunity -- kallikrein-kinin -- neutrophil extracellular traps -- neutrophils -- platelets -- SARS-CoV-2; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1097/MOH.0000000000000724
• Languages: English
• ISSNs: 1065-6251

Abstract

Abstract : Purpose of review: COVID-19 remains a major source of concern, particularly as new variants emerge and with recognition that patients may suffer long-term effects. Mechanisms underlying SARS-CoV-2 mediated organ damage and the associated vascular endotheliopathy remain poorly understood, hindering new drug development. Here, we highlight selected key concepts of how the complement system, a major component of innate immunity that is dysregulated in COVID-19, participates in the thromboinflammatory response and drives the vascular endotheliopathy. Recent findings: Recent studies have revealed mechanisms by which complement is activated directly by SARS-CoV-2, and how the system interfaces with other innate thromboinflammatory cellular and proteolytic pathways involving platelets, neutrophils, neutrophil extracellular traps and the coagulation and kallikrein-kinin systems. With this new information, multiple potential sites for therapeutic intervention are being uncovered and evaluated in the clinic. Summary: Infections with SARS-CoV-2 cause damage to the lung alveoli and microvascular endothelium via a process referred to as thromboinflammation. Although not alone in being dysregulated, complement is an early player, prominent in promoting the endotheliopathy and consequential organ damage, either directly and/or via the system's complex interplay with other cellular, molecular and biochemical pathways. Delineating these critical interactions is revealing novel and promising strategies for therapeutic intervention.