Figure 4. The strong relationship between the genes upregulated by vaccination and those downregulated during severe COVID-19.

(A) Overview of scRNA-Seq experiment on PBMCs from patients with COVID-19 with and without ARDS (n = 8 per group) and from healthy donors (n = 5). No participants were vaccinated against SARS-CoV-2 infection. (B) DEGs in monocytes identified by scRNA-Seq analysis of patients with COVID-19 with and without ARDS. Selected ISGs are annotated. (C) Circos plot of the overlapping genes among DEGs in monocytes detected for the BNT162b2 mRNA vaccine cohort and the unvaccinated COVID-19 cohort (P_adj < 0.05). In the vaccine cohort, DEGs detected at D1 and D22 relative to D0 and D20, respectively, were analyzed. In the COVID-19 cohort, DEGs detected in monocytes of ARDS patients compared with non-ARDS patients were analyzed. Each segment of the outer circle represents a monocyte subclass (Pan Mono, pan monocytes; cMono, classical monocytes; intMono, intermediate monocytes; or ncMono, nonclassical monocytes) and gene expression pattern (upregulated or downregulated). The inner circle colored in red (upregulated genes) and blue (downregulated genes) represents the genes that are shared by multiple segments, and the gray circle represents genes that are unique to that segment. On the inside, each arc represents a gene list. The arcs linking the Pan Mono segment with the cMono, intMono, or ncMono segment are colored. (D, E, and F) Scatter plots showing the overlapping genes identified by Circos plot. The y axis represents DEGs in cMono (D), intMono (E), and ncMono (F) in the COVID-19 cohort (non-ARDS versus ARDS). The x axis represents DEGs in pan monocytes in the vaccine cohort (D20 versus D22). Genes with significantly changed expression are marked in red (|log₂ fold change| > 1 and P_adj < 0.05 in both analyses). ARDS, acute respiratory distress syndrome; cMono, classical monocytes; intMono, intermediate monocytes; ncMono, nonclassical monocytes.