Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study

Background: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laborator...

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Autores: Sánchez-Montalvá, Adrián, Álvarez-Sierra, Daniel, Martínez-Gallo, Mónica, Perurena-Prieto, Janire, Arrese-Muñoz, Iria, Ruiz-Rodríguez, Juan Carlos, Espinosa-Pereiro, Juan, Bosch-Nicolau, Pau, Martínez-Gómez, Xavier, Antón, Andrés, Martínez-Valle, Ferran, Riveiro-Barciela, Mar, Blanco-Grau, Albert, Rodríguez-Frías, Francisco, Castellano-Escuder, Pol, Poyatos-Canton, Elisabet, Bas-Minguet, Jordi, Martínez-Cáceres, Eva, Sànchez, Àlex (Sànchez Pla), Zurera-Egea, Coral, Teniente-Serra, Aina, Hernández-González, Manuel, Pujol-Borrell, Ricardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/195201
Acceso en línea:https://hdl.handle.net/2445/195201
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
COVID-19
Citoquines
Quimiocines
Citometria de fluxe
Cytokines
Chemokines
Flow cytometry
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spelling Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot studySánchez-Montalvá, AdriánÁlvarez-Sierra, DanielMartínez-Gallo, MónicaPerurena-Prieto, JanireArrese-Muñoz, IriaRuiz-Rodríguez, Juan CarlosEspinosa-Pereiro, JuanBosch-Nicolau, PauMartínez-Gómez, XavierAntón, AndrésMartínez-Valle, FerranRiveiro-Barciela, MarBlanco-Grau, AlbertRodríguez-Frías, FranciscoCastellano-Escuder, PolPoyatos-Canton, ElisabetBas-Minguet, JordiMartínez-Cáceres, EvaSànchez, Àlex (Sànchez Pla)Zurera-Egea, CoralTeniente-Serra, AinaHernández-González, ManuelPujol-Borrell, RicardoSARS-CoV-2COVID-19CitoquinesQuimiocinesCitometria de fluxeSARS-CoV-2COVID-19CytokinesChemokinesFlow cytometryBackground: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings: 1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. Conclusions: Laboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.Frontiers Media2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/195201Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.902837Frontiers in Immunology, 2022, num. 13https://doi.org/10.3389/fimmu.2022.902837cc-by (c) Sánchez-Montalvá, Adrián et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1952012026-05-27T06:46:51Z
dc.title.none.fl_str_mv Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
title Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
spellingShingle Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
Sánchez-Montalvá, Adrián
SARS-CoV-2
COVID-19
Citoquines
Quimiocines
Citometria de fluxe
SARS-CoV-2
COVID-19
Cytokines
Chemokines
Flow cytometry
title_short Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
title_full Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
title_fullStr Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
title_full_unstemmed Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
title_sort Exposing and Overcoming Limitations of clinical laboratory tests in COVID-19 by adding immunological parameters; A Retrospective cohort analysis and pilot study
dc.creator.none.fl_str_mv Sánchez-Montalvá, Adrián
Álvarez-Sierra, Daniel
Martínez-Gallo, Mónica
Perurena-Prieto, Janire
Arrese-Muñoz, Iria
Ruiz-Rodríguez, Juan Carlos
Espinosa-Pereiro, Juan
Bosch-Nicolau, Pau
Martínez-Gómez, Xavier
Antón, Andrés
Martínez-Valle, Ferran
Riveiro-Barciela, Mar
Blanco-Grau, Albert
Rodríguez-Frías, Francisco
Castellano-Escuder, Pol
Poyatos-Canton, Elisabet
Bas-Minguet, Jordi
Martínez-Cáceres, Eva
Sànchez, Àlex (Sànchez Pla)
Zurera-Egea, Coral
Teniente-Serra, Aina
Hernández-González, Manuel
Pujol-Borrell, Ricardo
author Sánchez-Montalvá, Adrián
author_facet Sánchez-Montalvá, Adrián
Álvarez-Sierra, Daniel
Martínez-Gallo, Mónica
Perurena-Prieto, Janire
Arrese-Muñoz, Iria
Ruiz-Rodríguez, Juan Carlos
Espinosa-Pereiro, Juan
Bosch-Nicolau, Pau
Martínez-Gómez, Xavier
Antón, Andrés
Martínez-Valle, Ferran
Riveiro-Barciela, Mar
Blanco-Grau, Albert
Rodríguez-Frías, Francisco
Castellano-Escuder, Pol
Poyatos-Canton, Elisabet
Bas-Minguet, Jordi
Martínez-Cáceres, Eva
Sànchez, Àlex (Sànchez Pla)
Zurera-Egea, Coral
Teniente-Serra, Aina
Hernández-González, Manuel
Pujol-Borrell, Ricardo
author_role author
author2 Álvarez-Sierra, Daniel
Martínez-Gallo, Mónica
Perurena-Prieto, Janire
Arrese-Muñoz, Iria
Ruiz-Rodríguez, Juan Carlos
Espinosa-Pereiro, Juan
Bosch-Nicolau, Pau
Martínez-Gómez, Xavier
Antón, Andrés
Martínez-Valle, Ferran
Riveiro-Barciela, Mar
Blanco-Grau, Albert
Rodríguez-Frías, Francisco
Castellano-Escuder, Pol
Poyatos-Canton, Elisabet
Bas-Minguet, Jordi
Martínez-Cáceres, Eva
Sànchez, Àlex (Sànchez Pla)
Zurera-Egea, Coral
Teniente-Serra, Aina
Hernández-González, Manuel
Pujol-Borrell, Ricardo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SARS-CoV-2
COVID-19
Citoquines
Quimiocines
Citometria de fluxe
SARS-CoV-2
COVID-19
Cytokines
Chemokines
Flow cytometry
topic SARS-CoV-2
COVID-19
Citoquines
Quimiocines
Citometria de fluxe
SARS-CoV-2
COVID-19
Cytokines
Chemokines
Flow cytometry
description Background: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings: 1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. Conclusions: Laboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/195201
url https://hdl.handle.net/2445/195201
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.902837
Frontiers in Immunology, 2022, num. 13
https://doi.org/10.3389/fimmu.2022.902837
dc.rights.none.fl_str_mv cc-by (c) Sánchez-Montalvá, Adrián et al., 2022
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Sánchez-Montalvá, Adrián et al., 2022
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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