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

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.

ICU-Acquired Colonization and Infection Related to Multidrug-Resistant Bacteria in COVID-19 Patients: A Narrative Review

“…Notably, there is a high incidence of lymphopenia affecting both B and T cell populations, with subsequent impacts on cellular and humoral responses. Furthermore, studies have also indicated the presence of monocyte dysfunction, whose intensity seemingly correlates with disease severity [ 42 , 43 , 44 , 45 ]. These immune alterations collectively contribute to the development of an immunodeficient state intrinsically linked to COVID-19, thereby rendering severe COVID-19 patients more susceptible to MDR infections.…”

Obesity in Severe COVID-19 Patients Has a Distinct Innate Immune Phenotype

“…The innate immune system has the crucial role of recognizing the virus and activate inflammatory pathways in order to mount an effective antiviral response and viral clearance [ 3 ]. However, evidence has shown the heterogeneity of the immune response in severe COVID-19, which can exhibit hyperinflammatory and/or immunosuppressive phenotypes in effector cells [ 2 , 4 , 5 , 6 , 7 ]. Limited studies have suggested that this altered innate immune response seems to be patient-dependent [ 2 ] and the different outcomes of SARS-CoV-2 infection may be influenced by preexisting comorbidities [ 8 , 9 , 10 ].…”