A refinement of this observation suggested that COVID-19 patients with plasma levels of SPP1 ≥ 108 ng/mL and S100A12 ≥ 59 ng/mL (cut-off values based on their medians in all COVID-19 patients) were predictive of those more likely to have severe respiratory distress (PaO2/FiO2 ≤ 200) compared with those with lower SPP1 and S100A12 levels (Figure 3E and Supplemental Figure 4B). This evidence concerns the gene SPP1 and COVID-19.