Study Utilizing Imaging Mass Cytometry Details Changes in Lung Tissue Architecture at the Single-Cell Level in Patients with COVID-19
Weill Cornell Medicine Researchers Utilize Fluidigm Hyperion Imaging System to Identify a Phenotype of Immune Cell Activity Distinct from Other Lung Infections
A Framework for Data-Driven Spatial Understanding of Lung Pathology to Inform New Treatment Approaches for COVID-19
Results of the study, which have not yet been peer-reviewed, are available online through the medRxiv pre-print service.
“The unique spatial aspects of Imaging Mass Cytometry enabled us to view not only the structure of the tissue but also the interplay between infected cells and the immune system in COVID-19 patients,” said
This study utilized the
Samples from COVID-19 patients were categorized as early or late depending on whether death occurred 16–30 days or 31–44 days after the onset of respiratory symptoms, respectively. The Hyperion Imaging System analysis generated 237 highly multiplexed images identified across all specimens.
Among key findings of the study:
- A significant reduction in alveolar lacunar space, increased immune infiltration, and apoptosis-mediated cell death were observed in all diseased samples compared with those from healthy lungs.
- Neutrophil infiltration was increased in ARDS and early COVID-19 compared with normal lung, but appeared to be a hallmark of bacterial pneumonia, while a high degree of inflammation, infiltration of interstitial macrophages, complement activation, and fibrosis was characteristic of COVID-19.
- While late COVID-19 disease specifically displays hallmarks of tissue healing, the high COVID-19 mortality rate suggests that complement-activation-induced damage to the lung in concert with other immunological factors may lead to abnormal blood clotting in the lungs, which can lead to death.
Study findings agree with other recent studies suggesting that a type of pathophysiological response found in patients with ARDS due to influenza or bacterial pneumonia is similar to that found in those with COVID-19. However, in contrast with those studies, the Weill Cornell Medicine findings suggest that the hyperinflammatory phenotype as assessed by cytokine levels in peripheral blood is specific to COVID-19.
These findings suggest that early interventions that reduce off-target immune response or activators of the complement cascade could improve outcomes for COVID-19 patients.
“Understanding the pathology of COVID-19 lung disease is essential for developing interventions and treatment regimens that can improve patient outcomes and reduce mortality,” said
“Our robust IMC platform is uniquely suited to exploring these interactions with single-cell resolution. Significantly, in this study, IMC analyses uncovered novel interactions and cellular phenotypes that add important new insights into mechanisms of COVID-19 pathology, and these insights may help drive clinical practices that can improve patient outcomes.”
About Imaging Mass Cytometry
Imaging Mass Cytometry is setting a new standard in tissue imaging, significantly simplifying high-multiplex panel design and eliminating the impact of tissue autofluorescence by using highly pure metal tags for which signals are separated by mass instead of by wavelength. Incorporating an easy-to-use immunohistochemistry workflow that simultaneously detects many proteins in a single scan, IMC is ideal for uncovering new insights in health and disease and empowering the development of better diagnostics and more effective therapies.
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