Complement and COVID-19 disease

In the last 12 months after the start of the pandemic caused by the novel betacoronavirus SARS-CoV-2, much of the global population has faced unprecedented health issues linked to coronavirus disease COVID-19. It has been established that around the 10th day of infection patients suffering from COVID-19 infection featuring overactivation of innate immunity, also called 'cytokine storm', are more likely to die. It was quickly recognized that complement activation is part of this process, as underlined by complement mediated thrombo-inflammation playing a significant role in the excessive mortality caused by thromboembolic complications. Moreover, a portion of SARS-CoV-2 infected patients has an unusual long course of disease with late complications, also called long COVID-19, a phenotype where sustained inflammation and complement activation are involved. We are interested to explore why only a few among the infected suffer from effects of this 'cytokine storm'. Are dysregulated inflammation and complement activation playing a role here? 

The past year brought together several researchers, pharmaceutical companies, and institutions to conduct high-quality multitudinous research resulting in exceptional interest in COVID-19 related projects. Quickly after the recognition of the potential role of complement activation in the immune pathogenesis of COVID-19, the use of complement inhibitors was implemented to decrease excess mortality, finally leading to the organization of formal clinical trials. Although the hopeful expectations of the positive outcome of these drug-repurposing studies seem to be supported by initial data, our current understanding of basic mechanisms about the role of complement in COVID-19 is limited. 

In this Research Topic we aim to bring together researchers from the complement field to build up a wide and comprehensive landscape of the various aspects of this system in COVID-19. We welcome the submission of Review, Original Research, Perspective, Clinical Trial and Case Report covering, but not limited to, the following sub-topics: 

(1) Our current understanding of the various causes and mechanisms leading to complement activation in COVID-19 disease

(2) The consequences of complement activation, and dysregulation of the complement system during COVID-19 disease

(3) The complex relationships between complement and coagulation-, fibrinolysis-, contact systems and how these systems are affected during COVID-19 infection

(4) Educative or exceptional case histories or small case-series studies focused on the complement activation and clinical outcome that may help to improve clinical care–and may support the planning of further research in this field.