Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

Abstract The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-mean...

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Main Authors: Eunyoung Emily Lee, Kyoung-Ho Song, Woochang Hwang, Sin Young Ham, Hyeonju Jeong, Jeong-Han Kim, Hong Sang Oh, Yu Min Kang, Eun Bong Lee, Nam Joong Kim, Bum Sik Chin, Jin Kyun Park
Format: Article
Language:English
Published: Nature Portfolio 2021-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-87668-z
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author Eunyoung Emily Lee
Kyoung-Ho Song
Woochang Hwang
Sin Young Ham
Hyeonju Jeong
Jeong-Han Kim
Hong Sang Oh
Yu Min Kang
Eun Bong Lee
Nam Joong Kim
Bum Sik Chin
Jin Kyun Park
author_facet Eunyoung Emily Lee
Kyoung-Ho Song
Woochang Hwang
Sin Young Ham
Hyeonju Jeong
Jeong-Han Kim
Hong Sang Oh
Yu Min Kang
Eun Bong Lee
Nam Joong Kim
Bum Sik Chin
Jin Kyun Park
author_sort Eunyoung Emily Lee
collection DOAJ
description Abstract The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.
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spelling doaj.art-45194ea1576e47ceb5940ef1dd612e282022-12-21T22:55:08ZengNature PortfolioScientific Reports2045-23222021-04-011111810.1038/s41598-021-87668-zPattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysisEunyoung Emily Lee0Kyoung-Ho Song1Woochang Hwang2Sin Young Ham3Hyeonju Jeong4Jeong-Han Kim5Hong Sang Oh6Yu Min Kang7Eun Bong Lee8Nam Joong Kim9Bum Sik Chin10Jin Kyun Park11Division of Rheumatology, Department of Internal Medicine, Uijeongbu Eulji Medical CenterDivision of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang HospitalData Science for Knowledge Creation Research Center, Seoul National UniversityDivision of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang HospitalDivision of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang HospitalDivision of Infectious Diseases, Department of Internal Medicine, Armed Forces Capital HospitalDivision of Infectious Diseases, Department of Internal Medicine, Armed Forces Capital HospitalDepartment of Infectious Diseases, Myongji HospitalDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Infectious Diseases, Department of Internal Medicine, Seoul National University HospitalDivision of Infectious Diseases, Department of Internal Medicine, National Medical CenterDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineAbstract The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.https://doi.org/10.1038/s41598-021-87668-z
spellingShingle Eunyoung Emily Lee
Kyoung-Ho Song
Woochang Hwang
Sin Young Ham
Hyeonju Jeong
Jeong-Han Kim
Hong Sang Oh
Yu Min Kang
Eun Bong Lee
Nam Joong Kim
Bum Sik Chin
Jin Kyun Park
Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
Scientific Reports
title Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
title_full Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
title_fullStr Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
title_full_unstemmed Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
title_short Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis
title_sort pattern of inflammatory immune response determines the clinical course and outcome of covid 19 unbiased clustering analysis
url https://doi.org/10.1038/s41598-021-87668-z
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