Overall, in our model, luminal BBB expression of ACE2 appears to operate as a molecular sponge, which can sequester a circulating virus and increase the proportion of luminal infection to and luminal viral secretion, which can then ultimately be managed and neutralized by the systemic immune response and counterintuitively play a role in protecting from SARS-CoV-2 transcytosis into the brain. Here, ACE2 is linked to infection.