Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia #MMPMID33217134
Nicolai L; Leunig A; Brambs S; Kaiser R; Joppich M; Hoffknecht ML; Gold C; Engel A; Polewka V; Muenchhoff M; Hellmuth JC; Ruhle A; Ledderose S; Weinberger T; Schulz H; Scherer C; Rudelius M; Zoller M; Keppler OT; Zwissler B; von Bergwelt-Baildon M; Kaab S; Zimmer R; Bulow RD; von Stillfried S; Boor P; Massberg S; Pekayvaz K; Stark K
J Thromb Haemost 2021[Feb]; 19 (2): 574-581 PMID33217134show ga
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.
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J+Thromb+Haemost 2021 ; 19 (2): 574-581
