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

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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.
Funding Information
  • Science Foundation Ireland (20/COV/0038, CIHR OV2—170357)
  • Trinity College Dublin (20/COV/0038, CIHR OV2—170357)
  • the Canadian Institutes of Health Research (20/COV/0038, CIHR OV2—170357)
  • the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (20/COV/0038, CIHR OV2—170357)
  • Research Nova Scotia (20/COV/0038, CIHR OV2—170357)
  • Atlantic Genome/Genome Canada (20/COV/0038, CIHR OV2—170357)
  • Li-Ka Shing Foundation (20/COV/0038, CIHR OV2—170357)
  • Dalhousie Medical Research Foundation (20/COV/0038, CIHR OV2—170357)

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