Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses

Hoepel, W.; Chen, H.-J.; Allahverdiyeva, S.; Manz, X.; Aman, J.; Bonta, P.; Brouwer, P.; de Taeye, S.; Caniels, T.; van der Straten, K.; Golebski, K.; Griffith, G.; Jonkers, R.; Larsen, M.; Linty, F.; Neele, A.; Nouta, J.; van Baarle, F.; van Drunen, C.; Vlaar, A.; de Bree, G.; Sanders, R.; Willemsen, L.; Wuhrer, M.; Bogaard, H. J.; van Gils, M.; Vidarsson, G.; de Winther, M. P. J.; den Dunnen, J.

doi:10.1101/2020.07.13.190140

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bioRxiv · 10.1101/2020.07.13.190140

Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses

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Abstract

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. One sentence summaryAnti-Spike IgG promotes hyper-inflammation.

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Hoepel, W., Chen, H.-J., Allahverdiyeva, S., Manz, X., Aman, J., Bonta, P., Brouwer, P., de Taeye, S., Caniels, T., van der Straten, K., Golebski, K., Griffith, G., Jonkers, R., Larsen, M., Linty, F., Neele, A., Nouta, J., van Baarle, F., van Drunen, C., Vlaar, A., de Bree, G., Sanders, R., Willemsen, L., Wuhrer, M., Bogaard, H. J., van Gils, M., Vidarsson, G., de Winther, M. P. J., den Dunnen, J.. 2020-07-13. Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses. https://doi.org/10.1101/2020.07.13.190140

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