Extended Data Fig. 5: SARS-CoV-2 pneumonia is characterized by a persistent interferon-response signature in alveolar macrophages.
From: Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia
a, k-means clustering of the 2,323 significantly variable genes (q < 0.05, likelihood-ratio test) across diagnosis, columns represent each individual patient, grouped by diagnosis and ordered by day from first intubation. ‘Infection status’ refers only to the COVID-19 and ‘other viral pneumonia’ groups; blanks in these groups refer to samples for which microbiology data were incomplete and infectious status could not be determined. ‘Viral infection only’ refers to viral pathogens as the only detected pathogen in a sample and ‘viral infection with bacterial/fungal superinfection’ refers to detection of a viral pathogen with one or more bacterial or fungal co-pathogens. Representative genes and GO biological processes are shown for each cluster. Column headers are colour-coded by diagnosis and duration of mechanical ventilation (white indicates chronically ventilated patients). b, Expression of selected genes between the groups. Expression of IL6 is not increased in any group. All significant comparisons are shown (q < 0.05, Wald test with FDR correction in DESeq2). c, WGCNA. d–f, Interferon-response signatures in alveolar macrophages from patients with COVID-19 gradually decrease over the course of disease. Correlation between average expression of genes from GO:0060337 type I interferon signalling pathway (R = −0.51, P = 5.7 × 10−6, Pearson correlation) (d), GO:0060333 interferon-γ-mediated signalling pathway (R = −0.22, P = 0.06, Pearson correlation) (e), module 15 of WGCNA (R = −0.40, P = 5.5 × 10−4, Pearson correlation) (f) and time on mechanical ventilation. Grey boundaries represent 95% confidence intervals. g, UMAP projections of all bulk RNA-seq samples. Average expression of WGCNA module 15 (left) and percent of CD3+ T cells in BAL (right) are shown by point area. h, Heat map demonstrating time-dependent changes in gene expression of the canonical interferon-response genes from module 15 from patients with positive outcomes (discharged home or inpatient facility), poor outcomes (discharged to a LTAC or deceased). i, Correlation between detection of SARS-CoV-2 reads and disease progression (ρ = −0.49, P = 8.3 × 10−4, Spearman correlation).
