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Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning

OBJECTIVE: Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce. METHOD: Measures of Complement Activ...

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Autores principales: Wiffen, Laura, D’Cruz, Leon Gerard, Brown, Thomas, Higenbottam, Tim W., Bernstein, Jonathan A., Campbell, Courtney, Moellman, Joseph, Ghosh, Debajyoti, Richardson, Clive, Weston-Davies, Wynne, Chauhan, Anoop J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508987/
https://www.ncbi.nlm.nih.gov/pubmed/37731491
http://dx.doi.org/10.3389/fimmu.2023.1192765
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author Wiffen, Laura
D’Cruz, Leon Gerard
Brown, Thomas
Higenbottam, Tim W.
Bernstein, Jonathan A.
Campbell, Courtney
Moellman, Joseph
Ghosh, Debajyoti
Richardson, Clive
Weston-Davies, Wynne
Chauhan, Anoop J.
author_facet Wiffen, Laura
D’Cruz, Leon Gerard
Brown, Thomas
Higenbottam, Tim W.
Bernstein, Jonathan A.
Campbell, Courtney
Moellman, Joseph
Ghosh, Debajyoti
Richardson, Clive
Weston-Davies, Wynne
Chauhan, Anoop J.
author_sort Wiffen, Laura
collection PubMed
description OBJECTIVE: Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce. METHOD: Measures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO(2) > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan. RESULTS: The LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the “moderate” and “severe” categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study). CONCLUSION: Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery.
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spelling pubmed-105089872023-09-20 Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning Wiffen, Laura D’Cruz, Leon Gerard Brown, Thomas Higenbottam, Tim W. Bernstein, Jonathan A. Campbell, Courtney Moellman, Joseph Ghosh, Debajyoti Richardson, Clive Weston-Davies, Wynne Chauhan, Anoop J. Front Immunol Immunology OBJECTIVE: Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce. METHOD: Measures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO(2) > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan. RESULTS: The LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the “moderate” and “severe” categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study). CONCLUSION: Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery. Frontiers Media S.A. 2023-09-05 /pmc/articles/PMC10508987/ /pubmed/37731491 http://dx.doi.org/10.3389/fimmu.2023.1192765 Text en Copyright © 2023 Wiffen, D’Cruz, Brown, Higenbottam, Bernstein, Campbell, Moellman, Ghosh, Richardson, Weston-Davies and Chauhan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wiffen, Laura
D’Cruz, Leon Gerard
Brown, Thomas
Higenbottam, Tim W.
Bernstein, Jonathan A.
Campbell, Courtney
Moellman, Joseph
Ghosh, Debajyoti
Richardson, Clive
Weston-Davies, Wynne
Chauhan, Anoop J.
Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title_full Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title_fullStr Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title_full_unstemmed Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title_short Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
title_sort clinical severity classes in covid-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508987/
https://www.ncbi.nlm.nih.gov/pubmed/37731491
http://dx.doi.org/10.3389/fimmu.2023.1192765
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