We evaluated the transcriptional changes induced in the lungs of K18-hACE2 mice following infection with the ancestral B.1 lineage (Wuhan), B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.529 (Omicron) variants or mouse-adapted SARS-CoV-2 (MA10). Here, KRT18 is linked to infection.