SARS-CoV-2 neural infection depends on ACE2 and can be neutralized by anti-spike antibodies found in CSF of COVID-19 patients. (A) Immunofluorescence staining of ACE2 in brain organoids. Scale bar = 200 µm for zoomed-out images and 50 µm for zoomed-in images. (B) Immunofluorescence staining of organoids preincubated with isotype antibodies (top row) or anti-ACE2 antibodies (bottom row) and infected with SARS-CoV-2. Scale bar = 100 µm. (C) Schematic showing collection of clinical lumbar puncture from patients with and without COVID-19 for assays shown in D–F. (D) Quantification of anti–SARS-CoV-2 spike antibodies present in CSF of healthy versus COVID-19 patient in limiting dilution using ELISA. (E) Immunofluorescence staining of organoids infected with SARS-CoV-2 preincubated with CSF from health patients (top row) or CSF from COVID-19 patients (bottom row). Scale bar = 100 µm. (F) Quantification of figures from C and E. All experiments were performed with unique organoid, n = 4 per condition, from the same culturing batch, with images from n = 12 cortical regions with two IPSC lines, and Student’s t test was performed (****, P < 0.0001). Experiments were performed twice for reproducibility.