A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS

10.1101/2020.09.15.20195305

medRxiv

15th February 2021

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This research has not been peer-reviewed, and has been posted on pre-print repository medRxiv. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.


Abstract

Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with SARS-CoV-2. We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.

Author list:

Leila Reyes, Manuel A. Sanchez-Garcia, Tyler Morrison, Andrew J.M. Howden, Emily R. Watts, Simone Arienti, Pranvera Sadiku, Patricia Coelho, Ananda S. Mirchandani, Ailiang Zhang, David Hope, Sarah K. Clark, Jo Singleton, Shonna Johnston, Robert Grecian, Azin Poon, Sarah McNamara, Isla Harper, Max Head Fourman, Alejandro J. Brenes, Shalini Pathak, Amy Lloyd, Giovanny Rodriguez Blanco, Alex von Kriegsheim, Bart Ghesquiere, Wesley Vermaelen, Camila T. Cologna, Kevin Dhaliwal, Nik Hirani, David H. Dockrell, Moira K. B. Whyte, David Griffith, Doreen A. Cantrell, Sarah R. Walmsley.