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

Alexis Garduno; Gustavo Sganzerla Martinez; Ali Toloue Ostadgavahi; David Kelvin; Rachael Cusack; Ignacio Martin-Loeches

doi:10.3390/biomedicines11030778

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

Biomedicines. 2023 Mar 3;11(3):778. doi: 10.3390/biomedicines11030778.

Authors

Alexis Garduno¹, Gustavo Sganzerla Martinez², Ali Toloue Ostadgavahi², David Kelvin², Rachael Cusack³, Ignacio Martin-Loeches^{1

3

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Affiliations

¹ Department of Clinical Medicine, University of Dublin, Trinity College, D08 NHY1 Dublin, Ireland.
² Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada.
³ Department of Intensive Care Medicine, St. James's Hospital, James's Street, D08 NHY1 Dublin, Ireland.
⁴ Hospital Clinic, Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Ciberes, 08036 Barcelona, Spain.

Abstract

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.

Keywords: SARS-CoV-2; critically ill patients; immune silence; mild disease; monocyte dysregulation; peripheral blood mononuclear cells (PBMCs); secondary infection; sepsis; septic shock; single cell transcriptomics.

Abstract

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