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Organ-specific immune response in lethal SARS-CoV-2 infection by deep spatial phenotyping
Akhila Balachander1, Bernett Lee1, Subhra K Biswas1
1Singapore Immunology Network Agency for Science, Technology and Research (ASTAR) Singapore City Singapore.
Clinical & Translational Immunology
|May 23, 2022
Summary
COVID-19 causes multi-organ complications, even in young adults. This study used a novel technique to analyze immune responses in lung, heart, and intestine tissues, revealing significant inflammation and tissue damage.
Area of Science:
- Immunology
- Pathology
- Virology
Background:
- COVID-19 pathology extends beyond the lungs, affecting multiple organs.
- Mechanisms of multi-organ complications in COVID-19, particularly in younger adults without comorbidities, are not well understood.
Purpose of the Study:
- To investigate the spatial and functional patterns of immune response in lethal COVID-19 infection.
- To characterize immune, cytokine, and stromal cell status in pulmonary and extrapulmonary tissues of young adults with COVID-19.
Main Methods:
- Profiling of lung, heart, and intestinal autopsy samples from five SARS-CoV-2-infected cases.
- Utilized a novel IHC-based deep-phenotyping technique (immunoSpatial histoPhenOmics using TSA-IHC - iSPOT) for subcellular resolution analysis.
- Assessed 18-20 targets to detect immune, cytokine, and stromal cell status.
Main Results:
- SARS-CoV-2 infection led to skewed immune cell counts and organ-specific dysfunctions across all profiled tissues.
- Lung and ileal tissues showed architectural alterations and loss of tissue integrity.
- Lung and heart tissues exhibited severe hyperinflammation, with elevated TNF-α in the heart and elevated IL-6, IFN-γ, and IL-10 in the lungs.
Conclusions:
- Single-cell cytokine localization in immune and stromal structures offers mechanistic insights into organ-specific immunopathology.
- Findings are crucial for understanding naïve SARS-CoV-2 infection in younger populations without comorbidities.
- Highlights the importance of studying immune responses in extrapulmonary tissues during COVID-19.
