Fig. 12.

Scheme illustrating the effects of S protein on brain pericytes in absence of productive viral infection. Exposure of ACE2⁺ human brain vascular pericytes to SARS-CoV-2 S protein active trimer induces NF-κB signaling pathway and modulates intracellular Ca²⁺ activity. The intracellular signaling changes in brain pericytes upon S protein exposure are accompanied by an increased expression of contractile and myofibrogenic markers as well as secretion of inflammatory cytokines and chemokines. S protein effects are potentiated under hypoxic conditions, which are associated to vascular comorbidities that have been demonstrated to exacerbate COVID-19 pathogenesis. We postulate that SARS-CoV-2 could impair neurovascular functions by deregulating the functions of ACE2⁺ pericytes via S protein active trimer.