Although Lee et al. [7] showed that oral inoculation of SARS-CoV-2 can induce a milder pneumonia in hamsters, and lower viral load in the lungs than IN inoculation, we saw limited impact of the challenge routes in our study, possibly because the variant delivered to hamsters carried mutations in Spike (D614G and F367V), in ORF8 (S84L) and in ORF1ab (T5020I). This evidence concerns the gene CHMP5 and pneumonia.