Rationale for targeting complement in COVID-19.
Anastasia PolycarpouMark HowardConrad A FarrarRoseanna GreenlawGiorgia FanelliRussell WallisLinda S KlavinskisSteven H SacksPublished in: EMBO molecular medicine (2020)
A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.
Keyphrases
- sars cov
- acute respiratory distress syndrome
- respiratory syndrome coronavirus
- extracorporeal membrane oxygenation
- mechanical ventilation
- healthcare
- public health
- coronavirus disease
- emergency department
- systematic review
- intensive care unit
- anti inflammatory
- clinical trial
- acute kidney injury
- early onset
- liver failure
- lipopolysaccharide induced
- single cell
- drug induced
- lps induced
- cell therapy
- antimicrobial resistance
- stem cells
- cancer therapy
- mesenchymal stem cells
- human health
- multidrug resistant
- social media