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Nicolai, Leo; Leunig, Alexander; Brambs, Sophia; Kaiser, Rainer; Joppich, Markus; Hoffknecht, Marie-Louise; Gold, Christoph; Engel, Anouk; Polewka, Vivien; Muenchhoff, Maximilian; Hellmuth, Johannes C.; Ruhle, Adrian; Ledderose, Stephan; Weinberger, Tobias; Schulz, Heiko; Scherer, Clemens; Rudelius, Martina; Zoller, Michael; Keppler, Oliver T.; Zwissler, Bernhard; Bergwelt-Baildon, Michael von; Kääb, Stefan; Zimmer, Ralf; Buelow, Roman D.; Stillfried, Saskia von; Boor, Peter; Massberg, Steffen; Pekayvaz, Kami; Stark, Konstantin (2020): Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia. In: Journal of Thrombosis and Haemostasis, Vol. 19, No. 2: pp. 574-581
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Objective: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of coronavirus disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation. Approach and results By comparing histopathological specimens of SARS-CoV-2 with influenza-affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID-19, but less prominent in influenza pneumonia. Activated neutrophils were typically found in physical association with monocytes. To explore this further, we combined clinical data of COVID-19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA-seq data. We show that a HLADR(low) CD9(low) monocyte population expands in severe COVID-19, which releases neutrophil chemokines in the lungs, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID-19. Conclusions: Our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS-CoV-2 infection.