IsoPlexis’ Single-Cell Functional Proteomics Enables Identification of Key Immune Biomarkers of COVID-19

  • Researchers Su, et al. utilized IsoPlexis’ single-cell proteomics technology to identify a marked upregulation of polyfunctional cells with a variety of inflammatory cytokine secretions in both CD4+ and CD8+ T cells as well as in monocytes from patients with COVID-19 infection compared to healthy subjects.
  • IsoPlexis’ single-cell proteomics identified decreased polyfunctional strength index (PSI) of CD4+ and CD8+ T cells in ICU patients with increased proliferation and clonal expansion that positively correlated with COVID-19 disease severity when compared to non-ICU patients. Enhanced PSI of monocytes was also discovered in ICU patients with decreased antigen presentation and increased extravasation that was also associated with COVID-19 disease severity.
  • IsoPlexis’ functional proteomics uniquely revealed the upstream drivers of enhanced polyfunctional inflammatory monocytes in severe inflammation and marked downregulation of polyfunctional CD4+ T cells, particularly in ICU patients, providing novel mechanistic insights for COVID-19 pathogenesis and progression. The use of IsoPlexis’ functional proteomics platform precisely dissected polyfunctional heterogeneity and kinetics of peripheral immune cells, providing unique metrics and potential biomarkers for better understanding of COVID-19 infection and effective therapeutics development for early diagnosis and intervention.

 Single-Cell Analyses Identify Predictors of COVID-19 Disease Progression

A recent study published by Su, et al. used data from the Seattle COVID Consortium to demonstrate a significant association between several immune biomarkers and COVID-19 diagnosis and severity, including polyfunctionality of CD8+ T cells, CD4+ T cells, and monocytes, as defined by IsoPlexis’ single-cell functional proteomics. Researchers collected and analyzed peripheral blood mononuclear cells (PBMC) and plasma from 35 healthy and 50 COVID-19 patients, measuring the transcriptome, surface proteins, and T and B cell receptor sequences. The study, led by Dr. James Heath, president of the Institute for Systems Biology (ISB) examined immune markers of COVID-19 and disease progression, using IsoPlexis’ technology to assess the levels of 32 multiplexed chemokines and cytokines secreted from single CD4+ T cells, CD8+ T cells, and monocytes in COVID-19-diagnosed (ICU & non-ICU) and healthy samples. The results highlight key immune markers of COVID-19 infection and severe disease, and the significant heterogeneity of immune profiles among COVID-19 patients.

“Single-cell analytic methods have just begun to unravel the heterogeneous nature of immune dysregulation in COVID-19 patients. These have included analyses of airway epithelium-immune cell interactions where evidence for stronger interactions between epithelial cells and immune cells as disease severity increased, potentially providing insights into lung injury and respiratory failure seen in those patients.”1

IsoPlexis’ Single-Cell Proteomics Bridges COVID-19 Gaps

Researchers Su, et al. used IsoPlexis’ Single-Cell Secretome solution to identify a unique cytokine signature in COVID-19 patients who had been admitted to the ICU. These patients had upregulated functionally inflammatory monocytes that were unique and predictive sources of inflammation. These cells suppressed the CD4+ T cell function, leading to disease progression. It was determined that monocyte activation positively correlated with disease severity.1 Monocytes collected from healthy donors were also analyzed using IsoPlexis’ technology. When compared, the monocytes from patients diagnosed with COVID-19 demonstrated elevated functionality, and those who were in the ICU experienced a dramatic increase in polyfunctionality. These polyfunctional cell subsets were mostly effector, stimulatory, and inflammatory cytokines, which increased according to disease severity.1

Su, et al. also analyzed CD4+ and CD8+ T cells of healthy donors with IsoPlexis’ single-cell proteomics. Researchers noted CD4+ T cells from non-ICU COVID-19 patients (n = 34) were highly polyfunctional compared to healthy donors (n = 35), however the COVID-19 patients who were in the ICU (n= 16) demonstrated a loss in polyfunctionality, especially in the effector, stimulatory, and inflammatory cytokines. The CD8+ T cells from ICU patients also showed a decrease in polyfunctionality. The decrease in polyfunctionality suggests that severe disease may be associated with T cell exhaustion and dysregulated immune function affected by the polyfunctional suppressive monocytes.

IsoPlexis Reveals Unique Relationship Between Monocytes and T Cells in COVID-19 Patients in the ICU

In a recent webinar, Dr. James Heath, corresponding author of this paper, discusses his study a bit further. COVID-19 patients in the ICU were treated with Tocilizumab, which dramatically reduced the functionally inflammatory monocytes and in turn restored the functionality of the CD4+ T cells, and the patients recovered from COVID-19 infection. The functionally inflammatory monocyte cells are upstream drivers of inflammation in these ICU COVID-19 patients, suppressing the CD4+ T cells. These functionally inflammatory monocytes and suppressed T cells are determinants of COVID-19 reaction, and this relationship was uniquely revealed by IsoPlexis’ functional phenotyping.

IsoPlexis’ single-cell proteomics filled the functional gap of left by transcriptomics and flow cytometry, allowing researchers to obtain a comprehensive picture of the diverse immune profile of COVID-19 infection. IsoPlexis’ single-cell predictive profiling platform enabled the collection of data which advances researchers’ understanding of the immune profile of COVID-19 and key prognostic markers which have the potential to facilitate the development of effective therapeutic and preventative treatments.

IsoPlexis’ IsoLight proteomics hub uniquely provides an integrated solution for deep functional profiling of single-cells and highly-multiplexed ultra-small sample volumes. The IsoSpeak informatics software enables researchers to generate a precise, functional patient profile from this data to better understand and predict disease progression in infectious diseases such as COVID-19. To watch our recent webinar with Dr. James Heath on the use of single-cell proteomics in COVID-19 treatment and vaccine development, click here.

Reference:

  1. Su Y et al. Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories. Pre-Print, 2020.
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