None of them report reactivity against the S1 region or the receptor-binding domain (RBD), so the behavior of the pre-COVID-19 sera against the S protein could be due to cross-reactivity with the S2 region, in which shared epitopes have been found between SARS-CoV-2 and the known human coronavirus SARS-CoV, MERS-CoV, HCoV-HKU1, HCoV-OC43, HCoV-NL63, and HCoV-229E [22]. Here, PROS1 is linked to COVID-19.