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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , |
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| 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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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 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/195201 |
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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 |
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cc-by (c) Sánchez-Montalvá, Adrián et al., 2022 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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Frontiers Media |
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Frontiers Media |
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Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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