Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses
Amsterdam UMC COVID-19 Biobank,
Steven de Taeye,
Karlijn van der Straten,
Frank van Baarle,
Cornelis van Drunen,
Godelieve de Bree,
Harm Jan Bogaard,
Marit van Gils,
Menno de Winther,
Jeroen den Dunnen
Posted 13 Jul 2020
bioRxiv DOI: 10.1101/2020.07.13.190140
Posted 13 Jul 2020
For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk. ### Competing Interest Statement The authors have declared no competing interest.
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