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Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.
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; von Bergwelt-Baildon, Michael; Kääb, Stefan; Zimmer, Ralf; Bülow, Roman D; von Stillfried, Saskia; Boor, Peter; Massberg, Steffen; Pekayvaz, Kami; Stark, Konstantin.
  • Nicolai L; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Leunig A; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Brambs S; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Kaiser R; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Joppich M; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Hoffknecht ML; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Gold C; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Engel A; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Polewka V; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Muenchhoff M; Department of Informatics, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Hellmuth JC; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Ruhle A; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Ledderose S; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Weinberger T; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Schulz H; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Scherer C; Virology, Max von Pettenkofer Institute, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Rudelius M; German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
  • Zoller M; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Keppler OT; Medizinische Klinik und Poliklinik III, University Hospital LMU Munich, Munich, Germany.
  • Zwißler B; German Cancer Consortium (DKTK), Munich, Germany.
  • von Bergwelt-Baildon M; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Kääb S; Virology, Max von Pettenkofer Institute, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Zimmer R; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Bülow RD; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • von Stillfried S; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
  • Boor P; COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU, Munich, Germany.
  • Massberg S; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Pekayvaz K; Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
  • Stark K; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
J Thromb Haemost ; 19(2): 574-581, 2021 02.
Article in English | MEDLINE | ID: covidwho-939789
ABSTRACT

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 HLADRlow CD9low 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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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Thrombosis / Vasculitis / Influenza, Human / COVID-19 / Immunity, Innate / Lung / Neutrophils Subject: Thrombosis / Vasculitis / Influenza, Human / COVID-19 / Immunity, Innate / Lung / Neutrophils Language: English Journal: J Thromb Haemost Clinical aspect: Diagnosis / Prediction / Prognosis Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Main subject: Thrombosis / Vasculitis / Influenza, Human / COVID-19 / Immunity, Innate / Lung / Neutrophils Subject: Thrombosis / Vasculitis / Influenza, Human / COVID-19 / Immunity, Innate / Lung / Neutrophils Language: English Journal: J Thromb Haemost Clinical aspect: Diagnosis / Prediction / Prognosis Year: 2021
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