We evaluated the presence of specific antibodies (Abs) response against Human coronavirus NL63 (HCoV-NL63) S protein epitopes (NL63-RBM1, NL63-RBM2_1, NL63-RBM2_2, NL63-RBM3, NL63-SPIKE541–554, and NL63-DISC-like) and SARS-CoV-2 epitopes (COV2-SPIKE421–434 and COV2-SPIKE742–759) in plasma samples of pre-pandemic, mid-pandemic, and COVID-19 cohorts by indirect ELISA. This evidence concerns the gene PROS1 and COVID-19.