Scheme 1.

Schematic illustration of nanovesicles derived from bispecific CAR-T cells targeting the spike protein of SARS-CoV-2 for treating COVID-19. A, B Lentiviruses encoding CR3022/B38 CAR were obtained using a triplasmid lentivirus packaging system. C Lentiviruses infected T cells and CR3022/B38 CAR-T cells were collected. D Nanovesicles expressing CR3022/B38 scFv were prepared by extrusion. E CR3022/B38 NVs loaded with remdesivir by electroporation. F–G CR3022/B38 NVs prevented SARS-CoV-2 from entering cells expressing ACE2 at high levels by recognizing and binding specifically to the spike protein of SARS-CoV-2. H Remdesivir was released from CR3022/B38 NVs in the major sites of viral infection, and synergistically eliminated SARS-CoV-2 by inhibiting intracellular virus replication