Figure 6.
TF expression is associated with SARS-CoV-2 infection in vitro, in a murine infection model, and COVID-19 patients. TF expression (mRNA) or TF activity was assessed in vitro, in mice, and in plasma from human donors. (A) human TF (F3) mRNA expression quantified in SARS-CoV-2–infected A549 (ACE2) cells compared with uninfected (control) A549 (ACE2) cells. mRNA expression levels were normalized to RPP30. (B) Mouse TF (F3) gene expression determined by RNAseq in K18-ACE2tgn mouse lungs infected with SARS-CoV-2 on days 1, 3, 5, and 7 postinfection compared with uninfected K18-ACE2tgn mouse. To consider a differential gene expression statistically significant, thresholds of 0.01 and |log2(3)| were applied for the adjusted P value (P adj) and the minimum fold-change, respectively. N = 4 per group. (C) Human TF activity assessed in plasma from healthy donors (n = 15), COVID-19 patients with nonsevere (n = 25) or severe (n = 25) disease. TF activity was assessed by TF/FVII-mediated conversion of FX to FXa and subsequent conversion of FXa substrate. The specific TF activity indicated is calculated as total TF activity measured in the presence of control Ig minus the total TF activity measured in the presence of anti-TF antibody HTF-1. The numbers above the bars indicate the estimated TF activity in pM. Data are represented as mean ± SD. Statistical analysis: (A) Mann-Whitney test. (C) Kruskal-Wallis test followed by Dunn’s multiple comparison test. **P < .01. ns, not significant.