Fig. 5
Spike protein-CD147-CyPA axis contributes to COVID-19 cytokine storm. a SARS-CoV-2-infected VeroE6 cells with different titers were incubated for 48 h, and RNA was collected for CyPA detection by RT-qPCR (n = 3, Two-tailed student t test). b CD147 or ACE2 in VeroE6 cells was knocked out by CRISPR-Cas9, and the cells were then infected with SARS-CoV-2 for 48 h. The expression level of CyPA was detected by RT-qPCR (n = 3, Two-tailed student t test). c CD147 in VeroE6 cells was ectopically expressed by lentivirus, the cells were then infected with SARS-CoV-2 for 48 h with or without JAK inhibitor. The expression level of CyPA was detected by RT-qPCR (n = 3, Two-tailed student t test). d Heatmap of significantly upregulated genes based on RNA-seq. BEAS-2B cells were stimulated with or without CyPA for 48 h. Columns represent samples and rows represent genes. Gene expression levels in the heat maps are z score–normalized values determined by log2[CPM] values. e KEGG enrichment analysis of pathways enriched in upregulated genes from the CyPA-stimulated group compared with the control group. f Western blot analysis of p-p38, p-38, and c-FOS expression (n = 3, Two-tailed student t test, *p < 0.05). g IL-6 and CCL2 expression detected by RT-qPCR. h The heatmap of 32 differential cytokines. Fourty human cytokines were detected in plasma from healthy individuals (n = 100) and COVID-19 patients (n = 200, including 41 severe/critical and 159 mild) using cytokine chips. i CyPA protein detected in the plasma of healthy donors (n = 100), COVID-19 patients with mild symptoms (n = 159) and COVID-19 patients with severe/critical symptoms (n = 106) by ELISA (Two-tailed student t test). j Correlation analysis between CyPA and cytokines according to the Pearson correlation coefficient. Data were collected from the 41 severe/critical cases
