Figure 6.
A unique protein IFN signature characterizes the lower airways of COVID-19 patients compared to patients with other ARDS or noninfectious lung pathologies
(A–D) IFN-λ1 (A), IFN-λ2,3 (B), IFN-β (C), and IFN-α2 (D) protein levels were measured in the BALF of COVID-19 (BALF POS; 29, depicted with red dots), ARDS (BALF NEG ARDS; 5 were diagnosed H1N1 and are depicted with orange dots, and the remaining 4 are depicted with brown dots), non-microbially infected (BALF NEG CTRL; 10 affected by fibrosis are depicted with blue dots, 10 affected by sarcoidosis are depicted with green dots, and 10 transplant patients are depicted with purple dots). Each dot represents a patient. Median with range is depicted.
(E–J) IFN-λ1 (E), IFN-λ2,3 (F), IFN-β (G), IFN-α2 (H), IL-1β (I), and IL-6 (J) protein levels in the BALF of COVID-19 patients (17) are plotted against protein levels in the plasma of the same patient. Each dot represents a patient. Linear regression lines (continuous line) and 95% confidence interval (dashed line and shaded area) are depicted in red. Spearman correlation coefficients (r) and p value (p) are indicated.
(K) Heatmap comparison of IFN-α2, IFN-β, IFN-γ, IFN-λ1, IFN-λ2,3, IL-10, CXCL-10, IL-1β, IL-6, tumor necrosis factor (TNF), IL-8, and IL12p70 protein levels in the BALF of COVID-19 (29), ARDS (9), transplant (10), fibrosis (10), and sarcoidosis (10) patients. The color is proportional to the log10 transformed value of the amount of cytokine normalized for sample volume (picograms [pg]/lavage) of each cytokine. Rows in each group represent different patients. Unbiased K-means clustering was performed. Diagnosis, mortality, and age are annotated.
(L) Percentage of patients with the indicated diagnosis within clusters identified in (K).
(M–O) Odds ratio of containing COVID-19 patients in cluster 3 as compared to cluster 2 (M) and cluster 1 (N) and in cluster 2 as compared to cluster 1 (O) (clusters identified in J).
Statistics by Kruskal-Wallis test with Dunn’s post hoc test: ns, not significant (p > 0.05); ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001 (A–D) or chi-square test for odds ratio: ns, not significant (p > 0.05); ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001 (L–M). See also Figure S6 and Table S7.