- In a recent study published in Cell, IsoPlexis’ functional immune landscaping demonstrated 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 that peripheral CD8+ T cells in COVID-19 patients with moderate illness reflected the highest polyfunctionality and highest percentages of effector phenotypes.
- The Polyfunctional Strength Index (PSI) of peripheral monocytes increased with disease severity, suggesting the contribution of monocytes to the pro-inflammatory environment of moderate or severe COVID-19.
- IsoPlexis’ single-cell proteomics uniquely reveals the greatest polyfunctional upregulation of highly functional “supervillain” monocytes in severe illness of CD8+/CD4+ T cells in moderate illness, providing novel mechanistic insights for COVID-19 pathogenesis and progression.
- IsoPlexis functional immune landscaping precisely dissects 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.
IsoPlexis Improves Biomarker Characterization for Treatment, Monitoring, and Vaccine Development
COVID-19 presents with a wide range of symptoms, making it difficult to predict how infection will progress in each patient. With several potential COVID-19 therapeutics in clinical trials, biomarker detection allows clinicians to administer critical treatments at the early stages of the disease, and to tailor the therapy to the individual patient’s immune profile. IsoPlexis’ functional proteomics platform allows for complete functional immune landscaping with unique single-cell proteomics for biomarker detection. Researchers can use this technology to identify rare subsets of highly polyfunctional superpowered cells correlating with patient outcome and characterize the cytokines driving the immune response.
The severity of the inflammatory response caused by COVID-19 emphasizes the need for improved biomarkers. Infection begins when SARS-CoV-2 enters the body through the mouth, nose, or eyes and docs onto ACE2 receptors, found in various organ systems throughout the body. In the early stages of infection, cells release inflammatory signals that recruit macrophages, which release cytokines. If the infected person’s immune system is unable to overcome the infection, the virus can travel down to the lungs and attack the alveoli, the air sacs which regulate oxygen transfer throughout the body. Immune cells flock to the lungs to destroy the virus cells but leave behind fluid which can build up and cause pneumonia. Some patients develop acute respiratory distress syndrome (ARDS), a potentially fatal condition which requires external ventilation, or systemic inflammatory response syndrome (SIRS), leading to septic shock and organ failure. Identifying prognostic biomarkers of inflammation is critical to improving patient outcome.1
IsoPlexis Identifies Mechanisms of COVID-19 Infection and Disease Progression
Using IsoPlexis’ functional immune landscaping, researchers have identified immune biomarkers associated with COVID-19 infection or progression of disease severity from mild to moderate and severe. In a recent Cell publication, researchers Su, et al. used IsoPlexis’ unique single-cell proteomics to conduct deep functional immune profiling of COVID-19 patients ranging in disease severity compared to healthy samples. The researchers found that with increasing COVID-19 severity as measured by the WHO Ordinal Scale (WOS), CD4+ T cell, CD8+ T cell, and NK cell percentages dropped, while monocytes increased. Su, et al. noted a surprising similarity between healthy subjects and mild COVID-19 cases and between moderate and severe cases. The transition between mild and moderate disease was most significant and was marked by a significant drop in lymphocyte percentage and increase in monocyte percentage.2 IsoPlexis’ functional immune landscaping was able to shed insight into the functional mechanism behind this drop in lymphocyte percentage.
IsoPlexis’ functional immune landscaping was used to investigate the mechanism of COVID-19 inflammation within a variety of cell types. The severity of COVID-19 correlated with an increase of polyfunctionality in CD8+ T cells, followed by a significant drop in function at severe stages of the disease. Notably, the rare subsets of highly functional CD4+ T cells secreting IFN-γ, IL17-A, IL17-F, IL-4, and granzyme B are increased in COVID-19, and peak in moderate patients as well.2 “Unlike the case of CD8+ and CD4+ T cells, the PSI monotonically increases with disease severity, suggesting that monocytes contribute to the pro-inflammatory condition of moderate or severe COVID-19.”2
IsoPlexis Reveals Dysfunctional Monocyte Subset, Correlating with COVID-19 Severity
The marked increase of highly functional monocytes as COVID-19 severity increased suggests these cells play an important role. Researchers Su, et al. used IsoPlexis’ uniquely correlative metrics to assess the relationship between highly functional cell subsets and COVID-19 disease progression. Monocytes showed a sharp increase in function between the mild and moderate disease stages and the monocyte population and PSI continued to increase between moderate and severe cases.2 These findings suggest that monocytes may contribute to the pro-inflammatory environment that is characteristic of moderate and severe COVID-19 cases.
The successful treatment of infectious diseases such as COVID-19 requires a comprehensive understanding of the patient’s immune response to infection. Su, et al. studied a diverse cohort of COVID-19 patients and while mild cases were similar to healthy donors, there was a significant difference between mild and moderate cases.2 IsoPlexis’ functional phenotyping uniquely revealed the greatest polyfunctional upregulation of monocytes in severe illness and of CD8+/CD4+ T cells in moderate illness, providing novel mechanistic insights for COVID-19 pathogenesis and progression. In the Cell publication, Su, et al. suggested that the increase in polyfunctional inflammatory monocytes with disease severity was repressing T cell function in patients, explaining the decrease of T cell polyfunctionality between the moderate and severe stages and pointing to inflammatory monocytes as a potential therapeutic target for COVID-19 treatments.2 These unique insights facilitated the accelerated understanding of immune responses in COVID-19 patients, which is crucial to identifying the effectiveness of therapeutics.
The characterization of immune biomarkers at each stage of COVID-19 progression enables researchers to identify the most promising treatments and critical prognostic biomarkers. IsoPlexis’ technology helped detect a subset of functionally inflammatory monocytes that were driving disease progression and suppressing T cells, accelerating the comprehensive understanding of immune response. IsoPlexis’ unique single-cell proteomics is critical for the discovery of immune biomarkers which accelerate the fight against COVID-19, helping researchers and clinicians develop and identify promising treatments for patients. Watch a recent webinar from Dr. James Heath, the principal investigator of the study published in Cell, who discusses how IsoPlexis’ technology has helped identify prognostic biomarkers in the Seattle COVID Consortium.
- Wadman M. et al. How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes. Science Magazine, 2020
- Su Y et al. Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19. Cell, 2020.