Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing

Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understandin...

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Main Authors: Alexis Garduno, Gustavo Sganzerla Martinez, Ali Toloue Ostadgavahi, David Kelvin, Rachael Cusack, Ignacio Martin-Loeches
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/3/778
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author Alexis Garduno
Gustavo Sganzerla Martinez
Ali Toloue Ostadgavahi
David Kelvin
Rachael Cusack
Ignacio Martin-Loeches
author_facet Alexis Garduno
Gustavo Sganzerla Martinez
Ali Toloue Ostadgavahi
David Kelvin
Rachael Cusack
Ignacio Martin-Loeches
author_sort Alexis Garduno
collection DOAJ
description Critically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient’s clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide.
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spelling doaj.art-85312269d4254be5850092563299924b2023-11-17T09:45:28ZengMDPI AGBiomedicines2227-90592023-03-0111377810.3390/biomedicines11030778Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome SequencingAlexis Garduno0Gustavo Sganzerla Martinez1Ali Toloue Ostadgavahi2David Kelvin3Rachael Cusack4Ignacio Martin-Loeches5Department of Clinical Medicine, University of Dublin, Trinity College, D08 NHY1 Dublin, IrelandDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, CanadaDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, CanadaDepartment of Intensive Care Medicine, St. James’s Hospital, James’s Street, D08 NHY1 Dublin, IrelandDepartment of Clinical Medicine, University of Dublin, Trinity College, D08 NHY1 Dublin, IrelandCritically ill COVID-19 patients start developing single respiratory organ failure that often evolves into multiorgan failure. Understanding the immune mechanisms in severe forms of an infectious disease (either critical COVID-19 or bacterial septic shock) would help to achieve a better understanding of the patient’s clinical trajectories and the success of potential therapies. We hypothesized that a dysregulated immune response manifested by the abnormal activation of innate and adaptive immunity might be present depending on the severity of the clinical presentation in both COVID-19 and bacterial sepsis. We found that critically ill COVID-19 patients demonstrated a different clinical endotype that resulted in an inflammatory dysregulation in mild forms of the disease. Mild cases (COVID-19 and bacterial non severe sepsis) showed significant differences in the expression levels of CD8 naïve T cells, CD4 naïve T cells, and CD4 memory T cells. On the other hand, in the severe forms of infection (critical COVID-19 and bacterial septic shock), patients shared immune patterns with upregulated single-cell transcriptome sequencing at the following levels: B cells, monocyte classical, CD4 and CD8 naïve T cells, and natural killers. In conclusion, we identified significant gene expression differences according to the etiology of the infection (COVID-19 or bacterial sepsis) in the mild forms; however, in the severe forms (critical COVID-19 and bacterial septic shock), patients tended to share some of the same immune profiles related to adaptive and innate immune response. Severe forms of the infections were similar independent of the etiology. Our findings might promote the implementation of co-adjuvant therapies and interventions to avoid the development of severe forms of disease that are associated with high mortality rates worldwide.https://www.mdpi.com/2227-9059/11/3/778single cell transcriptomicscritically ill patientsSARS-CoV-2sepsisseptic shockimmune silence
spellingShingle Alexis Garduno
Gustavo Sganzerla Martinez
Ali Toloue Ostadgavahi
David Kelvin
Rachael Cusack
Ignacio Martin-Loeches
Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
Biomedicines
single cell transcriptomics
critically ill patients
SARS-CoV-2
sepsis
septic shock
immune silence
title Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
title_full Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
title_fullStr Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
title_full_unstemmed Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
title_short Parallel Dysregulated Immune Response in Severe Forms of COVID-19 and Bacterial Sepsis via Single-Cell Transcriptome Sequencing
title_sort parallel dysregulated immune response in severe forms of covid 19 and bacterial sepsis via single cell transcriptome sequencing
topic single cell transcriptomics
critically ill patients
SARS-CoV-2
sepsis
septic shock
immune silence
url https://www.mdpi.com/2227-9059/11/3/778
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