Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

Authors: Jan Cato Holter, Søren Erik Pischke, Eline de Boer, Andreas Lind, Synne Jenum, Aleksander Rygh Holten, Kristian Tonby, Andreas Barratt‐Due, Marina Sokolova, Camilla Schjalm, Viktoriia Chaban, Anette Kolderup, Trung Tran, Torleif Tollefsrud Gjølberg, Linda Gail Skeie, Liv Hesstvedt, Vidar Ormåsen, Børre Fevang, Cathrine Austad, Karl Erik Müller, Cathrine Fladeby, Mona Holberg‐Petersen, Bente Halvorsen, Fredrik Müller, Pål Aukrust, Susanne Dudman, Thor Ueland, Jan Terje Andersen, Fridtjof Lund‐Johansen, Lars Heggelund, Anne Ma Dyrhol‐Riise, Tom Eirik Mollnes - Proceedings of the National Academy of Sciences, PNAS 2020 cited by 419

Significance The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement activation occurs early in COVID-19 patients, and whether this is associated with respiratory failure. This study shows that a number of complement activation products are systemically, consistently, and long-lastingly increased from admission and during the hospital stay. Notably, the terminal sC5b-9 complement complex was associated with respiratory failure. Thus, complement inhibition is an attractive therapeutic approach for treatment of COVD-19.