Cross-talk between the airway epithelium and activated immune cells defines severity in COVID-19

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

Research Highlights 

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

Summary 

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

Study Type

· 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.