Amongst the above-mentioned factors, IFN-I and PAI-1 are dysregulated in older age, male gender, and preexisting diseases that are associated with increased risk to develop severe disease, and we propose the underexpression of IFN-I (and TLR7/TLR8) and the hypersecretion of PAI-1 as potential biomarkers to predict the susceptibility to severe COVID-19 (and maybe also other lung infections). This evidence concerns the gene SERPINE1 and COVID-19.