TY - JOUR
AU - Reyes, Leila
AU - Sanchez-Garcia, Manuel A.
AU - Morrison, Tyler
AU - Howden, Andy J. M.
AU - Watts, Emily R.
AU - Arienti, Simone
AU - Sadiku, Pranvera
AU - Coelho, Patricia
AU - Mirchandani, Ananda S.
AU - Zhang, Ailiang
AU - Hope, David
AU - Clark, Sarah K.
AU - Singleton, Jo
AU - Johnston, Shonna
AU - Grecian, Robert
AU - Poon, Azin
AU - McNamara, Sarah
AU - Harper, Isla
AU - Fourman, Max Head
AU - Brenes Murillo, Alejandro
AU - Pathak, Shalini
AU - Lloyd, Amy
AU - Rodriguez Blanco, Giovanny
AU - von Kriegsheim, Alexander
AU - Ghesquiere, Bart
AU - Vermaelen, Wesley
AU - Cologna, Camila T.
AU - Dhaliwal, Kevin
AU - Hirani, Nikhil
AU - Dockrell, David H.
AU - Whyte, Moira K. B.
AU - Griffith, David
AU - Cantrell, Doreen A.
AU - Walmsley, Sarah R.
PY - 2021
DA - February
TI - A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­
JO - Wellcome Open Research
VL - 6
DO - https://doi.org/10.12688/wellcomeopenres.16584.1
AB - Background: 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 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: 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. Results: 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. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.
PB - Wellcome Open Research
UR - https://discovery.dundee.ac.uk/en/publications/e510d9cf-8011-47ee-9e1e-ad902be80b8f
KW - Coronavirus (COVID-19)
ER