Fig. 3: Immunohistochemistry-, in situ hybridization- and electron microscopy-based detection of SARS-CoV within the olfactory mucosa.

a, CoV antigen detected by anti-SARS-CoV S protein antibodies (brown, individual P30) exhibits a cytoplasmic, often perinuclear, signal for CoV-positive cells resembling epithelial cells and cells harboring dendrite-like projections (arrowhead) with tips (arrows), which morphologically qualify as OSNs. b, SARS-CoV-2 RNA ISH showing intense signals in the mucus layer and cells (arrows) of the epithelium (asterisk) (brown, individual P15). c–f, Ultrastructural images of re-embedded FFPE material showing numerous extracellular CoV particles (c, arrows) attached to kinocilia (c, white asterisks) and intracellular CoV particles (d–f, increasing magnification) in a ciliated cell (individual P15, punch biopsy from the area in b). In e and f, intracellular CoV particles are located within cellular compartments of different sizes and are similar in their size and substructure. In f, at high magnification, five particles in this region show a particularly well-recognizable substructure (black arrows) that includes characteristic surface projections (black arrowhead), a heterogeneous and partly granular electron-dense interior, most likely representing RNP (white arrowheads), and a membrane envelope (white arrows). Scale bars: 20 µm (a), 50 µm (b), 1 µm (c), 2 µm (d), 500 nm (e) and 200 nm (f).