Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases

Nazlıhan Boyacı Dündar; David Sarphie; Kenan Yüce; Ümmügülsüm Gaygısız; O Tolga Kaskatı; Melda Türkoğlu; Gülbin Aygencel Bıkmaz; Lale Karabıyık; Kayhan Çağlar; Gülendam Bozdayı; Rubina Mian; Paul Moss; Mustafa Necmi İlhan

doi:10.1186/s40635-023-00554-y

Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases

Nazlıhan Boyacı Dündar^*, David Sarphie, Kenan Yüce, Ümmügülsüm Gaygısız, O Tolga Kaskatı, Melda Türkoğlu, Gülbin Aygencel Bıkmaz, Lale Karabıyık, Kayhan Çağlar, Gülendam Bozdayı, Rubina Mian, Paul Moss, Mustafa Necmi İlhan

^*Corresponding author for this work

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

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Abstract

Purpose: A prompt and effective immune response is required for clearance of pathogens but exaggerated states of inflammation can cause extensive collateral damage to the host. We have previously used a rapid near-patient assay that measures the functional capacity of neutrophils to produce reactive oxygen species (ROS) to show that values are elevated in patients with severe COVID-19 or sepsis. Here, we assess the utility of longitudinal ROS measurements to monitor and predict mortality outcome for patients with COVID-19 infection being treated in an ICU setting.

Methods: We used the Leukocyte ImmunoTest™ (LIT™) to quantify neutrophil ROS release using a small volume (10 µL) of capillary blood in a portable, rapid (10-min) format.

Results: ROS values (LIT score) and ROS levels assessed in relation to neutrophil count (LIT/N) were both markedly elevated in the patient group. Furthermore, these correlated strongly with peripheral neutrophil count and CRP value. Serial measurement of neutrophil or CRP values were not able to reliably predict mortality within the study. In contrast, LIT and LIT/N values started to decline at 7 and 5 days, respectively, in patients who survived ICU admission and this increment increased further thereafter.

Conclusions: This study raises the possibility of LIT and LIT/N to be used as a predictive clinical tool for patients with severe COVID-19 and argues for its assessment to inform on prognosis, and potentially guide treatment pathways, in other disorders associated with neutrophil activation.

Take-home message: A longitudinal study of 44 severe COVID-19 patients in the ICU of a leading teaching hospital has demonstrated the prognostic potential of a rapid bedside assay of neutrophil-derived reactive oxygen species (ROS). Assessment of changes in ROS production, as measured using the Leukocyte ImmunoTest™, shows that ROS production generally declined back to normal levels for patients who survived, but remained elevated for those patients who did not survive.

Original language	English
Article number	69
Number of pages	12
Journal	Intensive Care Medicine Experimental
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/s40635-023-00554-y
Publication status	Published - 6 Oct 2023

Bibliographical note

Funding:
The research was funded in part by Innovate UK, Project No. 56969, Project title: COVID-19: Development of novel algorithm-driven digital platform for assessing the Leukocyte ImmunoTest(TM) as a clinical parameter in monitoring vulnerability to coronavirus. In addition, this project has indirectly received funding from the European Union’s Horizon 2020 research and innovation programme under project INNO4COV-19 (Grant agreement No 101016203).

Copyright:
© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.

Keywords

Reactive oxygen species (ROS)
COVID-19
Leukocyte ImmunoTest
Neutrophil

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Dündar, N. B., Sarphie, D., Yüce, K., Gaygısız, Ü., Kaskatı, O. T., Türkoğlu, M., Bıkmaz, G. A., Karabıyık, L., Çağlar, K., Bozdayı, G., Mian, R., Moss, P., & İlhan, M. N. (2023). Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases. Intensive Care Medicine Experimental, 11(1), Article 69. https://doi.org/10.1186/s40635-023-00554-y

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abstract = "Purpose: A prompt and effective immune response is required for clearance of pathogens but exaggerated states of inflammation can cause extensive collateral damage to the host. We have previously used a rapid near-patient assay that measures the functional capacity of neutrophils to produce reactive oxygen species (ROS) to show that values are elevated in patients with severe COVID-19 or sepsis. Here, we assess the utility of longitudinal ROS measurements to monitor and predict mortality outcome for patients with COVID-19 infection being treated in an ICU setting. Methods: We used the Leukocyte ImmunoTest{\texttrademark} (LIT{\texttrademark}) to quantify neutrophil ROS release using a small volume (10 µL) of capillary blood in a portable, rapid (10-min) format. Results: ROS values (LIT score) and ROS levels assessed in relation to neutrophil count (LIT/N) were both markedly elevated in the patient group. Furthermore, these correlated strongly with peripheral neutrophil count and CRP value. Serial measurement of neutrophil or CRP values were not able to reliably predict mortality within the study. In contrast, LIT and LIT/N values started to decline at 7 and 5 days, respectively, in patients who survived ICU admission and this increment increased further thereafter. Conclusions: This study raises the possibility of LIT and LIT/N to be used as a predictive clinical tool for patients with severe COVID-19 and argues for its assessment to inform on prognosis, and potentially guide treatment pathways, in other disorders associated with neutrophil activation. Take-home message: A longitudinal study of 44 severe COVID-19 patients in the ICU of a leading teaching hospital has demonstrated the prognostic potential of a rapid bedside assay of neutrophil-derived reactive oxygen species (ROS). Assessment of changes in ROS production, as measured using the Leukocyte ImmunoTest{\texttrademark}, shows that ROS production generally declined back to normal levels for patients who survived, but remained elevated for those patients who did not survive.",

keywords = "Reactive oxygen species (ROS), COVID-19, Leukocyte ImmunoTest, Neutrophil",

author = "D{\"u}ndar, {Nazlıhan Boyacı} and David Sarphie and Kenan Y{\"u}ce and {\"U}mm{\"u}g{\"u}ls{\"u}m Gaygısız and Kaskatı, {O Tolga} and Melda T{\"u}rkoğlu and Bıkmaz, {G{\"u}lbin Aygencel} and Lale Karabıyık and Kayhan {\c C}ağlar and G{\"u}lendam Bozdayı and Rubina Mian and Paul Moss and İlhan, {Mustafa Necmi}",

note = "Funding: The research was funded in part by Innovate UK, Project No. 56969, Project title: COVID-19: Development of novel algorithm-driven digital platform for assessing the Leukocyte ImmunoTest(TM) as a clinical parameter in monitoring vulnerability to coronavirus. In addition, this project has indirectly received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under project INNO4COV-19 (Grant agreement No 101016203). Copyright: {\textcopyright} 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.",

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Dündar, NB, Sarphie, D, Yüce, K, Gaygısız, Ü, Kaskatı, OT, Türkoğlu, M, Bıkmaz, GA, Karabıyık, L, Çağlar, K, Bozdayı, G, Mian, R, Moss, P & İlhan, MN 2023, 'Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases', Intensive Care Medicine Experimental, vol. 11, no. 1, 69. https://doi.org/10.1186/s40635-023-00554-y

TY - JOUR

T1 - Assessing neutrophil-derived ROS production at the bedside

T2 - a potential prognostic tool in severe COVID-19 cases

AU - Dündar, Nazlıhan Boyacı

AU - Sarphie, David

AU - Yüce, Kenan

AU - Gaygısız, Ümmügülsüm

AU - Kaskatı, O Tolga

AU - Türkoğlu, Melda

AU - Bıkmaz, Gülbin Aygencel

AU - Karabıyık, Lale

AU - Çağlar, Kayhan

AU - Bozdayı, Gülendam

AU - Mian, Rubina

AU - Moss, Paul

AU - İlhan, Mustafa Necmi

N1 - Funding: The research was funded in part by Innovate UK, Project No. 56969, Project title: COVID-19: Development of novel algorithm-driven digital platform for assessing the Leukocyte ImmunoTest(TM) as a clinical parameter in monitoring vulnerability to coronavirus. In addition, this project has indirectly received funding from the European Union’s Horizon 2020 research and innovation programme under project INNO4COV-19 (Grant agreement No 101016203). Copyright: © 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.

PY - 2023/10/6

Y1 - 2023/10/6

N2 - Purpose: A prompt and effective immune response is required for clearance of pathogens but exaggerated states of inflammation can cause extensive collateral damage to the host. We have previously used a rapid near-patient assay that measures the functional capacity of neutrophils to produce reactive oxygen species (ROS) to show that values are elevated in patients with severe COVID-19 or sepsis. Here, we assess the utility of longitudinal ROS measurements to monitor and predict mortality outcome for patients with COVID-19 infection being treated in an ICU setting. Methods: We used the Leukocyte ImmunoTest™ (LIT™) to quantify neutrophil ROS release using a small volume (10 µL) of capillary blood in a portable, rapid (10-min) format. Results: ROS values (LIT score) and ROS levels assessed in relation to neutrophil count (LIT/N) were both markedly elevated in the patient group. Furthermore, these correlated strongly with peripheral neutrophil count and CRP value. Serial measurement of neutrophil or CRP values were not able to reliably predict mortality within the study. In contrast, LIT and LIT/N values started to decline at 7 and 5 days, respectively, in patients who survived ICU admission and this increment increased further thereafter. Conclusions: This study raises the possibility of LIT and LIT/N to be used as a predictive clinical tool for patients with severe COVID-19 and argues for its assessment to inform on prognosis, and potentially guide treatment pathways, in other disorders associated with neutrophil activation. Take-home message: A longitudinal study of 44 severe COVID-19 patients in the ICU of a leading teaching hospital has demonstrated the prognostic potential of a rapid bedside assay of neutrophil-derived reactive oxygen species (ROS). Assessment of changes in ROS production, as measured using the Leukocyte ImmunoTest™, shows that ROS production generally declined back to normal levels for patients who survived, but remained elevated for those patients who did not survive.

AB - Purpose: A prompt and effective immune response is required for clearance of pathogens but exaggerated states of inflammation can cause extensive collateral damage to the host. We have previously used a rapid near-patient assay that measures the functional capacity of neutrophils to produce reactive oxygen species (ROS) to show that values are elevated in patients with severe COVID-19 or sepsis. Here, we assess the utility of longitudinal ROS measurements to monitor and predict mortality outcome for patients with COVID-19 infection being treated in an ICU setting. Methods: We used the Leukocyte ImmunoTest™ (LIT™) to quantify neutrophil ROS release using a small volume (10 µL) of capillary blood in a portable, rapid (10-min) format. Results: ROS values (LIT score) and ROS levels assessed in relation to neutrophil count (LIT/N) were both markedly elevated in the patient group. Furthermore, these correlated strongly with peripheral neutrophil count and CRP value. Serial measurement of neutrophil or CRP values were not able to reliably predict mortality within the study. In contrast, LIT and LIT/N values started to decline at 7 and 5 days, respectively, in patients who survived ICU admission and this increment increased further thereafter. Conclusions: This study raises the possibility of LIT and LIT/N to be used as a predictive clinical tool for patients with severe COVID-19 and argues for its assessment to inform on prognosis, and potentially guide treatment pathways, in other disorders associated with neutrophil activation. Take-home message: A longitudinal study of 44 severe COVID-19 patients in the ICU of a leading teaching hospital has demonstrated the prognostic potential of a rapid bedside assay of neutrophil-derived reactive oxygen species (ROS). Assessment of changes in ROS production, as measured using the Leukocyte ImmunoTest™, shows that ROS production generally declined back to normal levels for patients who survived, but remained elevated for those patients who did not survive.

KW - Reactive oxygen species (ROS)

KW - COVID-19

KW - Leukocyte ImmunoTest

KW - Neutrophil

U2 - 10.1186/s40635-023-00554-y

DO - 10.1186/s40635-023-00554-y

M3 - Article

C2 - 37801184

SN - 2197-425X

VL - 11

JO - Intensive Care Medicine Experimental

JF - Intensive Care Medicine Experimental

IS - 1

M1 - 69

ER -

Assessing neutrophil-derived ROS production at the bedside: a potential prognostic tool in severe COVID-19 cases

Abstract

Bibliographical note

Keywords

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