Figure 5.
PASC-related cytokine triad in acute COVID-19 and profiling of IL1B, IL6, and TNF signatures in different tissues from hospitalized COVID-19 patients or individuals with mild to moderate COVID-19 courses
(A) Median plasma levels of IL-1β, IL6, and TNF in acute COVID-19 (n = 20) and in post-acute disease phases (n = 471) as compared with patients with bacterial pneumonia (n = 5) or individuals without prior COVID-19 (n = 96). Samples from patients with bacterial pneumonia and acute COVID-19 derived from the HACO trial; follow-up blood samples derived from DigiHero and the HACO trial. Bars indicate 95% confidence interval.
(B) Profiling of IL1B, IL6, and TNF transcripts in lung autopsy tissue from deceased COVID-19 patients. Single-cell transcriptome dataset from Delorey et al.39
(C) Macrophage subsets from bronchoalveolar (BAL) fluid in active COVID-19. Integrated single-cell dataset from Zhao et al.,40 Wendisch et al.,41 and Liao et al.42 encompassing 19,089 cells. Uniform Manifold Approximation and Projection (UMAP) plot showing expression of IL1B, IL6, and TNF in macrophage subpopulations.
(D) Analysis of gene set associated with response to cytokine triad in macrophage subsets from bronchoalveolar fluid in active COVID-19.
(E) Generation of an integrated peripheral blood mononuclear cell (PBMC) dataset encompassing 39 healthy individuals (140,472 cells), 50 COVID-19 patients with mild (167,160 cells) and 19 with severe (81,754 cells) courses with data derived from Stephenson et al.,43 Schulte-Schrepping et al.,44 and Su et al.45
(F) Expression of IL1B, IL6, TNF, and their receptors IL1R1, IL1R2, IL6R, TNFRSF1A, and TNFRSF1B in monocytes relative to the remaining cells in the integrated datasets from (E) shown as a dotplot.