急性呼吸窘迫综合征
医学
补体系统
免疫学
凝集素途径
弥漫性肺泡损伤
替代补体途径
肺
抗体
内科学
急性呼吸窘迫
作者
Youssif M Ali,George Carnell,Stefano Fumagalli,Domenico Mercurio,Serena Seminara,Nicholas J. Lynch,Priyanka Khatri,Chanuka H Arachchilage,Luca Mascheroni,Clemens F. Kaminski,Charlotte George,Hazel Stewart,Munehisa Yabuki,Gregory Demopulos,Jonathan L. Heeney,Wilhelm Schwaeble
标识
DOI:10.1093/infdis/jiad462
摘要
Most COVID-19 patients requiring ICU care develop an acute respiratory distress syndrome (ARDS), characterised by severe hypoxemia, decreased lung compliance, and high vascular permeability. Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins reported in inflamed tissue and on the endothelium during COVID-19. Using a transgenic mouse model of SARS-CoV-2 infection we assessed the therapeutic utility of an inhibitory antibody (HG4) targeting the lectin pathway key enzyme MASP-2. Treatment of infected mice with HG4 reduced the disease severity score and improved survival compared to mice that received an isotype control antibody. Administration of HG4 significantly reduced the lung injury score including alveolar inflammatory cell infiltration, alveolar oedema and alveolar haemorrhage. The overall ameliorating effect of MASP-2 inhibition on the severity of COVID-19 pathology is reflected by a significant reduction in the pro-inflammatory activation of brain microglia in HG4 treated mice.
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