Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients
Objectives:. Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 pa...
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Wolters Kluwer
2020
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oai:doaj.org-article:cccc0cb28a5d481eb92f663806d7c95a2021-11-25T07:52:09ZNovel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients2639-802810.1097/CCE.0000000000000189https://doaj.org/article/cccc0cb28a5d481eb92f663806d7c95a2020-09-01T00:00:00Zhttp://journals.lww.com/10.1097/CCE.0000000000000189https://doaj.org/toc/2639-8028Objectives:. Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers. Design:. Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins. Setting:. Tertiary care ICU and academic laboratory. Subjects:. All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive). Interventions:. None. Measurements and Main Results:. Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 [CD83], family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0; p = 0.007). Conclusions:. Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality.Douglas D. Fraser, MD, PhDGediminas Cepinskas, DVM, PhDEric K. Patterson, PhDMarat Slessarev, MD, MScClaudio Martin, MD, MScMark Daley, PhDMaitray A. Patel, BScMichael R. Miller, PhDDavid B. O’Gorman, PhDSean E. Gill, PhDGuillaume Pare, MD, MScIoannis Prassas, PhDEleftherios Diamandis, MD, PhDon behalf of the Lawson COVID19 Study TeamRobert ArntfieldIan BallGordon BarkwellTracey BentallKaren BosmaSaoirse CameronEileen CampbellDavid CarterCarolina Gillio-MeinaRobert HegeleNatalya OdoardiRam SinghKelly SummersSue TereschynWolters KluwerarticleMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENCritical Care Explorations, Vol 2, Iss 9, p e0189 (2020) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 |
| spellingShingle |
Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Douglas D. Fraser, MD, PhD Gediminas Cepinskas, DVM, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Claudio Martin, MD, MSc Mark Daley, PhD Maitray A. Patel, BSc Michael R. Miller, PhD David B. O’Gorman, PhD Sean E. Gill, PhD Guillaume Pare, MD, MSc Ioannis Prassas, PhD Eleftherios Diamandis, MD, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| description |
Objectives:. Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers.
Design:. Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins.
Setting:. Tertiary care ICU and academic laboratory.
Subjects:. All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive).
Interventions:. None.
Measurements and Main Results:. Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 [CD83], family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0; p = 0.007).
Conclusions:. Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality. |
| format |
article |
| author |
Douglas D. Fraser, MD, PhD Gediminas Cepinskas, DVM, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Claudio Martin, MD, MSc Mark Daley, PhD Maitray A. Patel, BSc Michael R. Miller, PhD David B. O’Gorman, PhD Sean E. Gill, PhD Guillaume Pare, MD, MSc Ioannis Prassas, PhD Eleftherios Diamandis, MD, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn |
| author_facet |
Douglas D. Fraser, MD, PhD Gediminas Cepinskas, DVM, PhD Eric K. Patterson, PhD Marat Slessarev, MD, MSc Claudio Martin, MD, MSc Mark Daley, PhD Maitray A. Patel, BSc Michael R. Miller, PhD David B. O’Gorman, PhD Sean E. Gill, PhD Guillaume Pare, MD, MSc Ioannis Prassas, PhD Eleftherios Diamandis, MD, PhD on behalf of the Lawson COVID19 Study Team Robert Arntfield Ian Ball Gordon Barkwell Tracey Bentall Karen Bosma Saoirse Cameron Eileen Campbell David Carter Carolina Gillio-Meina Robert Hegele Natalya Odoardi Ram Singh Kelly Summers Sue Tereschyn |
| author_sort |
Douglas D. Fraser, MD, PhD |
| title |
Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| title_short |
Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| title_full |
Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| title_fullStr |
Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| title_full_unstemmed |
Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses of Plasma From Critically Ill Coronavirus Disease 2019 Patients |
| title_sort |
novel outcome biomarkers identified with targeted proteomic analyses of plasma from critically ill coronavirus disease 2019 patients |
| publisher |
Wolters Kluwer |
| publishDate |
2020 |
| url |
https://doaj.org/article/cccc0cb28a5d481eb92f663806d7c95a |
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