High generation of reactive oxygen species from neutrophils in patients with severe COVID-19

Abstract Neutrophilia and an elevated neutrophil:lymphocyte ratio are both characteristic features of severe COVID-19 infection. However, functional neutrophil responses have been poorly investigated in this setting. We utilised a novel PMA-based stimulation assay to determine neutrophil-derived rea...

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Main Authors: Tonny Veenith, Helena Martin, Martin Le Breuilly, Tony Whitehouse, Fang Gao-Smith, Niharika Duggal, Janet M. Lord, Rubina Mian, David Sarphie, Paul Moss
Format: Article
Language:English
Published: Nature Portfolio 2022-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-13825-7
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author Tonny Veenith
Helena Martin
Martin Le Breuilly
Tony Whitehouse
Fang Gao-Smith
Niharika Duggal
Janet M. Lord
Rubina Mian
David Sarphie
Paul Moss
author_facet Tonny Veenith
Helena Martin
Martin Le Breuilly
Tony Whitehouse
Fang Gao-Smith
Niharika Duggal
Janet M. Lord
Rubina Mian
David Sarphie
Paul Moss
author_sort Tonny Veenith
collection DOAJ
description Abstract Neutrophilia and an elevated neutrophil:lymphocyte ratio are both characteristic features of severe COVID-19 infection. However, functional neutrophil responses have been poorly investigated in this setting. We utilised a novel PMA-based stimulation assay to determine neutrophil-derived reactive oxygen species (ROS) generation in patients with severe COVID-19 infection, non-COVID related sepsis and healthy study participants. ROS production was markedly elevated in COVID-19 patients with median values ninefold higher than in healthy controls and was particularly high in patients on mechanical ventilation. ROS generation correlated strongly with neutrophil count and elevated levels were also seen in patients with non-COVID related sepsis. Relative values, adjusted for neutrophil count, were high in both groups but extreme low or high values were seen in two patients who died shortly after testing, potentially indicating a predictive value for neutrophil function. Our results show that the high levels of neutrophils observed in patients with COVID-19 and sepsis exhibit functional capacity for ROS generation. This may contribute to the clinical features of acute disease and represents a potential novel target for therapeutic intervention.
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spelling doaj.art-2cd7f35aea034eb6a1e1caa21fcb1c9f2022-12-22T02:38:28ZengNature PortfolioScientific Reports2045-23222022-06-011211910.1038/s41598-022-13825-7High generation of reactive oxygen species from neutrophils in patients with severe COVID-19Tonny Veenith0Helena Martin1Martin Le Breuilly2Tony Whitehouse3Fang Gao-Smith4Niharika Duggal5Janet M. Lord6Rubina Mian7David Sarphie8Paul Moss9Institute of Inflammation and Ageing, University of BirminghamUniversity Hospitals Birmingham NHS Foundation TrustUniversity Hospitals Birmingham NHS Foundation TrustUniversity Hospitals Birmingham NHS Foundation TrustInstitute of Inflammation and Ageing, University of BirminghamInstitute of Inflammation and Ageing, University of BirminghamInstitute of Inflammation and Ageing, University of BirminghamSeroxo LimitedSeroxo LimitedInstitute of Immunology and Immunotherapy, University of BirminghamAbstract Neutrophilia and an elevated neutrophil:lymphocyte ratio are both characteristic features of severe COVID-19 infection. However, functional neutrophil responses have been poorly investigated in this setting. We utilised a novel PMA-based stimulation assay to determine neutrophil-derived reactive oxygen species (ROS) generation in patients with severe COVID-19 infection, non-COVID related sepsis and healthy study participants. ROS production was markedly elevated in COVID-19 patients with median values ninefold higher than in healthy controls and was particularly high in patients on mechanical ventilation. ROS generation correlated strongly with neutrophil count and elevated levels were also seen in patients with non-COVID related sepsis. Relative values, adjusted for neutrophil count, were high in both groups but extreme low or high values were seen in two patients who died shortly after testing, potentially indicating a predictive value for neutrophil function. Our results show that the high levels of neutrophils observed in patients with COVID-19 and sepsis exhibit functional capacity for ROS generation. This may contribute to the clinical features of acute disease and represents a potential novel target for therapeutic intervention.https://doi.org/10.1038/s41598-022-13825-7
spellingShingle Tonny Veenith
Helena Martin
Martin Le Breuilly
Tony Whitehouse
Fang Gao-Smith
Niharika Duggal
Janet M. Lord
Rubina Mian
David Sarphie
Paul Moss
High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
Scientific Reports
title High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
title_full High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
title_fullStr High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
title_full_unstemmed High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
title_short High generation of reactive oxygen species from neutrophils in patients with severe COVID-19
title_sort high generation of reactive oxygen species from neutrophils in patients with severe covid 19
url https://doi.org/10.1038/s41598-022-13825-7
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