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Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study

Sivakumar Oruganti Orcid Logo, Patrícia R S Rodrigues Orcid Logo, Daniel White, William John Watkins, Selyf Shapey, Anna Barrow, Rim al Samsam, Sara Ali, Malcolm Gajraj, Richard Skone, Michelle Jardine, Jennifer Evans, Siske Struik, Jong Eun Song, Lloyd Abood, Barbara Paquete, Sian Foulkes, Benjamin Saunders, Angela Strang, Sarah Joanne Kotecha, Bethan Phillips, Awen Evans, Iona Buchanan, Susan Bowes, Begum Ali, Maya Gore, Rhian Thomas-Turner, Robert Andrews, Summia Zaher, Simran Sharma Orcid Logo, Mallinath Chakraborty Orcid Logo, Edward Parkinson, Federico Liberatore, Thomas Woolley, Sarah Edkins, Luke Davies Orcid Logo, Linda Moet, James E McLaren, Gareth L Watson, Valerie O'Donnell, Kerry Hood, Peter Ghazal Orcid Logo

BMJ Open, Volume: 13, Issue: 3, Start page: e067002

Swansea University Author: Luke Davies Orcid Logo

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Abstract

Introduction Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system’s biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infe...

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Published in: BMJ Open
ISSN: 2044-6055 2044-6055
Published: BMJ 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa67960
first_indexed 2024-11-25T14:21:11Z
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A previous system&#x2019;s biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age.Methods and analysis We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 &#x3BC;L each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent.Ethics and dissemination The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites.</abstract><type>Journal Article</type><journal>BMJ Open</journal><volume>13</volume><journalNumber>3</journalNumber><paginationStart>e067002</paginationStart><paginationEnd/><publisher>BMJ</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>2044-6055</issnPrint><issnElectronic>2044-6055</issnElectronic><keywords/><publishedDay>27</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-03-27</publishedDate><doi>10.1136/bmjopen-2022-067002</doi><url/><notes>Protocol</notes><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Other</apcterm><funders>The study has received funding from the Welsh Government- EU ERDF for Ser Cymru II programme grant (East Wales ERDF Programme grant number 80762- CU- 106) for Project Sepsis (PG). PRSR was supported in part by MRC (R520481) to PG.</funders><projectreference/><lastEdited>2024-12-18T16:47:46.1337448</lastEdited><Created>2024-10-11T09:00:35.9872049</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Sivakumar</firstname><surname>Oruganti</surname><orcid>0000-0003-1384-2664</orcid><order>1</order></author><author><firstname>Patr&#xED;cia R S</firstname><surname>Rodrigues</surname><orcid>0000-0003-0768-0013</orcid><order>2</order></author><author><firstname>Daniel</firstname><surname>White</surname><order>3</order></author><author><firstname>William John</firstname><surname>Watkins</surname><order>4</order></author><author><firstname>Selyf</firstname><surname>Shapey</surname><order>5</order></author><author><firstname>Anna</firstname><surname>Barrow</surname><order>6</order></author><author><firstname>Rim al</firstname><surname>Samsam</surname><order>7</order></author><author><firstname>Sara</firstname><surname>Ali</surname><order>8</order></author><author><firstname>Malcolm</firstname><surname>Gajraj</surname><order>9</order></author><author><firstname>Richard</firstname><surname>Skone</surname><order>10</order></author><author><firstname>Michelle</firstname><surname>Jardine</surname><order>11</order></author><author><firstname>Jennifer</firstname><surname>Evans</surname><order>12</order></author><author><firstname>Siske</firstname><surname>Struik</surname><order>13</order></author><author><firstname>Jong Eun</firstname><surname>Song</surname><order>14</order></author><author><firstname>Lloyd</firstname><surname>Abood</surname><order>15</order></author><author><firstname>Barbara</firstname><surname>Paquete</surname><order>16</order></author><author><firstname>Sian</firstname><surname>Foulkes</surname><order>17</order></author><author><firstname>Benjamin</firstname><surname>Saunders</surname><order>18</order></author><author><firstname>Angela</firstname><surname>Strang</surname><order>19</order></author><author><firstname>Sarah Joanne</firstname><surname>Kotecha</surname><order>20</order></author><author><firstname>Bethan</firstname><surname>Phillips</surname><order>21</order></author><author><firstname>Awen</firstname><surname>Evans</surname><order>22</order></author><author><firstname>Iona</firstname><surname>Buchanan</surname><order>23</order></author><author><firstname>Susan</firstname><surname>Bowes</surname><order>24</order></author><author><firstname>Begum</firstname><surname>Ali</surname><order>25</order></author><author><firstname>Maya</firstname><surname>Gore</surname><order>26</order></author><author><firstname>Rhian</firstname><surname>Thomas-Turner</surname><order>27</order></author><author><firstname>Robert</firstname><surname>Andrews</surname><order>28</order></author><author><firstname>Summia</firstname><surname>Zaher</surname><order>29</order></author><author><firstname>Simran</firstname><surname>Sharma</surname><orcid>0000-0002-6647-9355</orcid><order>30</order></author><author><firstname>Mallinath</firstname><surname>Chakraborty</surname><orcid>0000-0002-1721-6532</orcid><order>31</order></author><author><firstname>Edward</firstname><surname>Parkinson</surname><order>32</order></author><author><firstname>Federico</firstname><surname>Liberatore</surname><order>33</order></author><author><firstname>Thomas</firstname><surname>Woolley</surname><order>34</order></author><author><firstname>Sarah</firstname><surname>Edkins</surname><order>35</order></author><author><firstname>Luke</firstname><surname>Davies</surname><orcid>0000-0001-7767-4060</orcid><order>36</order></author><author><firstname>Linda</firstname><surname>Moet</surname><order>37</order></author><author><firstname>James E</firstname><surname>McLaren</surname><order>38</order></author><author><firstname>Gareth L</firstname><surname>Watson</surname><order>39</order></author><author><firstname>Valerie</firstname><surname>O'Donnell</surname><order>40</order></author><author><firstname>Kerry</firstname><surname>Hood</surname><order>41</order></author><author><firstname>Peter</firstname><surname>Ghazal</surname><orcid>0000-0003-0035-2228</orcid><order>42</order></author></authors><documents/><OutputDurs/></rfc1807>
spelling 2024-12-18T16:47:46.1337448 v2 67960 2024-10-11 Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study ff080296775381560053d5e3a6e81745 0000-0001-7767-4060 Luke Davies Luke Davies true false 2024-10-11 MEDS Introduction Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system’s biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age.Methods and analysis We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 μL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent.Ethics and dissemination The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. Journal Article BMJ Open 13 3 e067002 BMJ 2044-6055 2044-6055 27 3 2023 2023-03-27 10.1136/bmjopen-2022-067002 Protocol COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Other The study has received funding from the Welsh Government- EU ERDF for Ser Cymru II programme grant (East Wales ERDF Programme grant number 80762- CU- 106) for Project Sepsis (PG). PRSR was supported in part by MRC (R520481) to PG. 2024-12-18T16:47:46.1337448 2024-10-11T09:00:35.9872049 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Sivakumar Oruganti 0000-0003-1384-2664 1 Patrícia R S Rodrigues 0000-0003-0768-0013 2 Daniel White 3 William John Watkins 4 Selyf Shapey 5 Anna Barrow 6 Rim al Samsam 7 Sara Ali 8 Malcolm Gajraj 9 Richard Skone 10 Michelle Jardine 11 Jennifer Evans 12 Siske Struik 13 Jong Eun Song 14 Lloyd Abood 15 Barbara Paquete 16 Sian Foulkes 17 Benjamin Saunders 18 Angela Strang 19 Sarah Joanne Kotecha 20 Bethan Phillips 21 Awen Evans 22 Iona Buchanan 23 Susan Bowes 24 Begum Ali 25 Maya Gore 26 Rhian Thomas-Turner 27 Robert Andrews 28 Summia Zaher 29 Simran Sharma 0000-0002-6647-9355 30 Mallinath Chakraborty 0000-0002-1721-6532 31 Edward Parkinson 32 Federico Liberatore 33 Thomas Woolley 34 Sarah Edkins 35 Luke Davies 0000-0001-7767-4060 36 Linda Moet 37 James E McLaren 38 Gareth L Watson 39 Valerie O'Donnell 40 Kerry Hood 41 Peter Ghazal 0000-0003-0035-2228 42
title Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
spellingShingle Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
Luke Davies
title_short Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
title_full Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
title_fullStr Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
title_full_unstemmed Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
title_sort Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study
author_id_str_mv ff080296775381560053d5e3a6e81745
author_id_fullname_str_mv ff080296775381560053d5e3a6e81745_***_Luke Davies
author Luke Davies
author2 Sivakumar Oruganti
Patrícia R S Rodrigues
Daniel White
William John Watkins
Selyf Shapey
Anna Barrow
Rim al Samsam
Sara Ali
Malcolm Gajraj
Richard Skone
Michelle Jardine
Jennifer Evans
Siske Struik
Jong Eun Song
Lloyd Abood
Barbara Paquete
Sian Foulkes
Benjamin Saunders
Angela Strang
Sarah Joanne Kotecha
Bethan Phillips
Awen Evans
Iona Buchanan
Susan Bowes
Begum Ali
Maya Gore
Rhian Thomas-Turner
Robert Andrews
Summia Zaher
Simran Sharma
Mallinath Chakraborty
Edward Parkinson
Federico Liberatore
Thomas Woolley
Sarah Edkins
Luke Davies
Linda Moet
James E McLaren
Gareth L Watson
Valerie O'Donnell
Kerry Hood
Peter Ghazal
format Journal article
container_title BMJ Open
container_volume 13
container_issue 3
container_start_page e067002
publishDate 2023
institution Swansea University
issn 2044-6055
2044-6055
doi_str_mv 10.1136/bmjopen-2022-067002
publisher BMJ
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Introduction Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system’s biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age.Methods and analysis We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 μL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent.Ethics and dissemination The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites.
published_date 2023-03-27T08:35:19Z
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