Cross-talk between the airway epithelium and activated immune cells defines severity in COVID-19
bioinformatics cell biology clinical diagnostics immunology/immunity inflammation molecular biology therapeutics
Authors: Chua et al.
Link to paper: https://doi.org/10.1101/2020.04.29.20084327
Journal/ Pre-Print: medRxiv
Tags: Immunology/Immunity, Bioinformatics, Cell Biology, Clinical/ Diagnostics, Inflammation, Molecular Biology, Therapeutics
1. More severe COVID-19 patients have different immune cell enrichment in airways than moderate patients
2. Chemokines and pro-inflammatory cytokines more highly expressed in severe than moderate patients
3. Correlation between CTL-epithelial cell interaction and ACE2 expression
Samples were taken from the respiratory tract of patients with moderate or severe COVID-19, and single-cell RNAseq performed to compare the two groups. Critical patients had a depletion of basal cells and enrichment for neutrophils compared with moderate patients. Predicted intercellular interactions based on expression of receptor-ligand pairs were higher in severe than in moderate patient samples, with increased immune-epithelial cell interaction positively correlating with higher immune cell activation status. Chemokine and pro-inflammatory cytokine genes were significantly more expressed in severe patients. CTLs from moderate cases displayed a typical anti-viral transcriptional profile whereas CTLs from severe cases had higher cytotoxic potential but lower cytokine expression.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Understand the virology and/or cell biology of SARS-CoV2/COVID19
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19
Treat of SARS-CoV2/COVID19 positive individuals
· In silico study / bioinformatics study
· Patient Case study
Strengths and limitations of the paper
Novelty: Comprehensive transcriptomics of immune and epithelial cells in COVID-19 patients
Standing in the field: In agreement with other recent studies showing hyperactivation of immune system in more severe cases
Appropriate statistics: Yes
Viral model used: patients with confirmed SARS-CoV-2 infection
Translatability: Suggests therapies to selectively block recruitment of certain immune cells might be beneficial
Main limitations: Small cohort (5 moderate patients and 9 critical patients); the authors make strong claims about their data and infer mechanisms beyond the scope of their results; predicted rather than actual intercellular interactions shown; correlations depicted as causal.