(A) In influenza virus infection, abundant airway and alveolar epithelial cell expression of ɑ2,6-linked sialic acid residues, the receptors for influenza viruses, enables a rapid spread across the lung and a short clinical course. Injury, viral clearance, and alveolar fibrosis or repair occur synchronously over the course of the illness. (B and C) In SARS-CoV-2 infection, sparse ACE2 expression results in spatially restricted areas of normal lung, ongoing injury, viral clearance, and alveolar fibrosis or repair in different lung regions.