Proteomics identifies a type I IFN, prothrombotic hyperinflammatory circulating COVID-19 neutrophil signature distinct from non-COVID-19 ARDS

10.1101/2020.09.15.20195305

medRxiv

8th 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This research has not been peer-reviewed, and has been posted on pre-print repository medRxiv.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

Understanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress syndrome (ARDS) is of significant clinical interest given the mortality associated with severe and critical coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS, but a relative paucity of these cells is observed at post-mortem in lung tissue of patients who succumb to infection with SARS-CoV-2. With emerging evidence of a dysregulated innate immune response in COVID-19, we undertook a functional proteomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS, non-COVID-19 ARDS, moderate COVID-19, and healthy controls. We observe that expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in both COVID-19 and non-COVID-19 ARDS. In contrast, release of neutrophil granule proteins, neutrophil activation of the clotting cascade and formation of neutrophil platelet aggregates is significantly increased in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I IFN responses is specific to infection with SARS-CoV-2 and linked to metabolic rewiring. Together this work highlights how differential activation of circulating neutrophil populations may contribute to the pathogenesis of ARDS, identifying processes that are specific to COVID-19 ARDS.

Author list:

Leila Reyes, Manuel Alejandro Sanchez-Garcia, Tyler Morrison, Andrew JM Howden, Emily R Watts, Simone Arienti, Pranvera Sadiku, Patricia Coelho, Ananda S Mirchandani, 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, Gio Rodriguez Blanco, Alex Von Kriegsheim, Bart Ghesquiere, Wesley Vermaelen, Camila T Cologna, Kevin Dhaliwal, Nik Hirani, David Dockrell, Moira KB Whyte, David M Griffith, Doreen A Cantrell, Sarah R Walmsley