Although the lowering of circulating LDL-cholesterol levels may reduce cholesterol levels of peripheral cells and monocyte inflammation (Stiekema et al, 2021; Xie et al, 2022), the PCSK9 blockade improving COVID-19 outcomes cannot be easily explained by up-regulation of LDL receptor–mediated endocytosis and cellular cholesterol levels, a setting that would rather support COVID-19 infectivity. This evidence concerns the gene PCSK9 and COVID-19.