Fig. 5: Correlation of ISGhigh and ISGlow lung immunoprofiles with morphological changes.
From: Two distinct immunopathological profiles in autopsy lungs of COVID-19
a Expression of a cytokine signature (TNF, IL-1B, IL6, IFNA17, IFNB1, CCL2, CXCL9, CXCL10, CXCL11) in ISGhigh and ISGlow COVID-19 lung samples. This pro-inflammatory cytokine signature was significantly enriched in the ISGhigh subset (n = 31 independent samples). b Inverse correlation of viral load and activated CD8+ T cell signature (CD38, GZMA, GZMB, CCR5). Solid lines connect sample points from the same patient. The dotted line shows a regression for all the samples, and the gray area delimits the 95% Confidence Intervals around it (Pearson’s correlation = −0.5, adjusted R-squared = 0.22, p-value = 0.005). c Association of DAD stage with ISG expression (n = 31 independent samples). d Association of the pro-inflammatory cytokine signature with intra-alveolar hemorrhage (IAH) (n = 31 independent samples). e Pearson’s correlation of pro-inflammatory cytokines in the cytokine signature indicates the presence of co-regulated cytokines. f–i Association of cytokine signatures in ISGhigh and ISGlow COVID-19 lung samples with IAH. Association of: f Median IL6, TNF, IL1B expression. g Median IFNA17, IFNB1 expression. h Median CCL2 expression. i Median CXCL9/10/11 expression in ISGhigh and ISGlow COVID-19 lung samples versus IAH. Only the CXCL9/10/11 sub-signature was positively associated with IAH (n = 31 independent samples). j Association of CD68+ macrophage infiltrates with DAD (n = 27 independent samples). k Association of DAD stage with activated CD8+ T cell signature (n = 31 independent samples), l with CD8+ T cell counts (n = 29). m–p Association of cytokine signatures in ISGhigh and ISGlow COVID-19 lung samples with DAD stage. Association of: m Median IL6, TNF, IL1B expression. n Median IFNA17, IFNB1 expression. o Median CCL2 expression. p Median CXCL9/10/11 expression in ISGhigh and ISGlow COVID-19 lung tissue with DAD stage (n = 31 independent samples). ISGhigh samples, red; ISGlow samples, blue. All box-plots elements indicate the median (center line), upper and lower quartiles (box limits). Whiskers extend to the most extreme value included in 1.5× interquartile range. Groups were compared using a two-sided Wilcoxon rank-sum test.
