Platelet-adenovirus aggregates are taken up by macrophages in the spleen. (A) Images of X649 endogenous platelet labeling mice 24 hours after IM and IV ChAdOx1 nCov-19 administration. Cut out of red pulp to follicle transition is shown on the upper left. Stars are next to GPIb + agglomerations that are morphologically reminiscent of platelet remnants. Scale bars for overview are 50 µm and for cut outs are 10 µm. Quantification of platelet (×649) area in the marginal and follicle zone as percent of marginal and follicular area. n = 4 per group, unpaired t test. (B) Quantification of platelet-F4/80 co-localization in the splenic red pulp. Colocalization is shown as percent of total platelet-F4/80 area. n = 4 per group, unpaired t test. (C) 3D reconstruction of in vivo microscopy of the spleen with transfused platelets pretreated with either ChAdOx1 nCov-19 (white) or PBS (green). ChAdOx1 nCov-19 pretreated platelets are taken up by F4/80⁺/CD169⁺ macrophages, whereas control treated platelets are not. Scale bar is 5 µm. (D) Platelet tracking parameters of intraviral imaging. n = 31 platelets tracked per group of 1 mouse. Ten exemplary tracked paths per group are shown on the left as x and y displacement; ticks signify 5-µm intervals. Unpaired t test with Welch’s correction. Error bars are mean ± SEM. **P < .01; ***P < .001.