Multivariate indicators of disease severity in COVID-19

Abstract The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying su...

Full description

Bibliographic Details
Main Authors: Joe Bean, Leticia Kuri-Cervantes, Michael Pennella, Michael R. Betts, Nuala J. Meyer, Wail M. Hassan
Format: Article
Language:English
Published: Nature Portfolio 2023-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-31683-9
_version_ 1827974603872403456
author Joe Bean
Leticia Kuri-Cervantes
Michael Pennella
Michael R. Betts
Nuala J. Meyer
Wail M. Hassan
author_facet Joe Bean
Leticia Kuri-Cervantes
Michael Pennella
Michael R. Betts
Nuala J. Meyer
Wail M. Hassan
author_sort Joe Bean
collection DOAJ
description Abstract The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying such divergent disease outcomes. Multivariate modeling was used here to define the most distinctive features that separate COVID-19 from healthy controls and severe from moderate disease. Using discriminant analysis and binary logistic regression models we could distinguish between severe disease, moderate disease, and control with rates of correct classifications ranging from 71 to 100%. The distinction of severe and moderate disease was most reliant on the depletion of natural killer cells and activated class-switched memory B cells, increased frequency of neutrophils, and decreased expression of the activation marker HLA-DR on monocytes in patients with severe disease. An increased frequency of activated class-switched memory B cells and activated neutrophils was seen in moderate compared to severe disease and control. Our results suggest that natural killer cells, activated class-switched memory B cells, and activated neutrophils are important for protection against severe disease. We show that binary logistic regression was superior to discriminant analysis by attaining higher rates of correct classification based on immune profiles. We discuss the utility of these multivariate techniques in biomedical sciences, contrast their mathematical basis and limitations, and propose strategies to overcome such limitations.
first_indexed 2024-04-09T19:57:03Z
format Article
id doaj.art-f88aa008d52d4790bc0be4aace6049b5
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-09T19:57:03Z
publishDate 2023-03-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-f88aa008d52d4790bc0be4aace6049b52023-04-03T05:25:55ZengNature PortfolioScientific Reports2045-23222023-03-0113112810.1038/s41598-023-31683-9Multivariate indicators of disease severity in COVID-19Joe Bean0Leticia Kuri-Cervantes1Michael Pennella2Michael R. Betts3Nuala J. Meyer4Wail M. Hassan5Department of Biomedical Sciences, School of Medicine, University of Missouri – Kansas CityDepartment of Microbiology, Perelman School of Medicine, University of PennsylvaniaDepartment of Biomedical Sciences, School of Medicine, University of Missouri – Kansas CityDepartment of Microbiology, Perelman School of Medicine, University of PennsylvaniaDivision of Pulmonary, Allergy and Critical Care, Department of Medicine, Center for Translational Lung Biology, Lung Biology Institute, Perelman School of Medicine, University of PennsylvaniaDepartment of Biomedical Sciences, School of Medicine, University of Missouri – Kansas CityAbstract The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying such divergent disease outcomes. Multivariate modeling was used here to define the most distinctive features that separate COVID-19 from healthy controls and severe from moderate disease. Using discriminant analysis and binary logistic regression models we could distinguish between severe disease, moderate disease, and control with rates of correct classifications ranging from 71 to 100%. The distinction of severe and moderate disease was most reliant on the depletion of natural killer cells and activated class-switched memory B cells, increased frequency of neutrophils, and decreased expression of the activation marker HLA-DR on monocytes in patients with severe disease. An increased frequency of activated class-switched memory B cells and activated neutrophils was seen in moderate compared to severe disease and control. Our results suggest that natural killer cells, activated class-switched memory B cells, and activated neutrophils are important for protection against severe disease. We show that binary logistic regression was superior to discriminant analysis by attaining higher rates of correct classification based on immune profiles. We discuss the utility of these multivariate techniques in biomedical sciences, contrast their mathematical basis and limitations, and propose strategies to overcome such limitations.https://doi.org/10.1038/s41598-023-31683-9
spellingShingle Joe Bean
Leticia Kuri-Cervantes
Michael Pennella
Michael R. Betts
Nuala J. Meyer
Wail M. Hassan
Multivariate indicators of disease severity in COVID-19
Scientific Reports
title Multivariate indicators of disease severity in COVID-19
title_full Multivariate indicators of disease severity in COVID-19
title_fullStr Multivariate indicators of disease severity in COVID-19
title_full_unstemmed Multivariate indicators of disease severity in COVID-19
title_short Multivariate indicators of disease severity in COVID-19
title_sort multivariate indicators of disease severity in covid 19
url https://doi.org/10.1038/s41598-023-31683-9
work_keys_str_mv AT joebean multivariateindicatorsofdiseaseseverityincovid19
AT leticiakuricervantes multivariateindicatorsofdiseaseseverityincovid19
AT michaelpennella multivariateindicatorsofdiseaseseverityincovid19
AT michaelrbetts multivariateindicatorsofdiseaseseverityincovid19
AT nualajmeyer multivariateindicatorsofdiseaseseverityincovid19
AT wailmhassan multivariateindicatorsofdiseaseseverityincovid19