FIGURE 1 COVID-19 patient lungs exhibit mucus plugs and pathological changes in the airway epithelium. Chest x-ray obtained on January 12, 2020 (A1), on January 17, 2020 (B1) and on January 22, 2020 (C1). Representative lung CT images on January 13, 2020 (D1) and (E1). Representative transverse lung CT images on January 23, 2020 (F1) and (G1). Chest x-ray obtained on January 30, 2020 (H1), on February 01, 2020 (I1) and on February 15, 2020 (J1). K1) Representative images of lung tissue sections stained with hematoxylin and eosin from the COVID-19 patient. Asterisks indicate airways. L1) Representative images of lung tissue sections stained with periodic acid-Schiff from the COVID-19 patient. The arrows point to goblet cells. Asterisks indicate mucus plugs in the airways. M1) Immunostaining for MUC5AC (green) and DAPI staining (blue) of sections of larger distal bronchioles from healthy controls (n=3) and the COVID-19 patient. The arrow points to the mucus plug. The arrow head points to the goblet cell. N1) Quantification of the number of larger distal bronchioles plugged by mucus in healthy controls (n=3) and the COVID-19 patient. O1) Quantification of the number of larger distal bronchioles with MCU5AC+ cells in healthy controls (n=3) and the COVID-19 patient. P1) Immunostaining for MUC5AC (green) and DAPI staining (blue) of sections of the smaller distal bronchioles from healthy controls (n=3) and the COVID-19 patient. The arrow points to the mucus plug. Q1) Quantification of the number of smaller distal bronchioles plugged by mucus in healthy controls (n=3) and the COVID-19 patient. R1) Quantification of the number of smaller distal bronchioles with MCU5AC+ cells in healthy controls (n=3) and the COVID-19 patient. A2) Relative MUC5AC mRNA levels in the lungs from healthy controls and the COVID-19 patient. B2) Immunostaining for MUC5B (red) and DAPI staining (blue) of sections of the airways from healthy controls (n=3) and the COVID-19 patient. C2) Quantification of mean fluorescence intensity of MUC5B immunostaining in the airways in healthy controls (n=3) and the COVID-19 patient. D2) Relative MUC5B mRNA levels in the lungs from healthy controls and the COVID-19 patient. E2) Immunostaining for acetylated alpha-tubulin (green) and DAPI staining (blue) of sections of small bronchioles from healthy controls (n=3) and the COVID-19 patient. F2) Quantification of the relative number of acetylated alpha-tubulin+ multiciliated cells in small bronchioles in healthy controls (n=3) and the COVID-19 patient. G2) Immunostaining for CC16 (red) and DAPI staining (blue) of sections of distal bronchioles from healthy controls (n=3) and the COVID-19 patient. H2) Quantification of the relative number of CC16+ cells in distal bronchioles in healthy controls (n=3) and the COVID-19 patient. I2) Relative CC16 mRNA levels in the lungs from healthy controls and the COVID-19 patient. J2) Quantification of CC16 levels in serum from healthy controls (n=7) and severe and critical COVID-19 patients (n=9). K2) Immunostaining for IL-13 (red) and DAPI staining (blue) of sections of the lungs from healthy controls (n=3) and the COVID-19 patient. L2) Quantification of mean fluorescence intensity of IL-13 immunostaining in the lungs in healthy controls (n=3) and the COVID-19 patient. M2) Representative images of cross sections of ALI cultures stained with hematoxylin and eosin. The arrow points to cilia. N2) Trans-epithelial electrical resistance measurements. O2) Immunostaining for MUC5AC (red), SARS-CoV-2 N (green) and DAPI staining (blue) in HBE cells at the ALI after a 14-day differentiation. Scale bars: 100 μm (K1, L1, M1, P1, O2), 20 μm (B2, E2, G2, K2, M2). SARS-CoV-2 N: SARS-CoV-2 nucleocapsid proteins. *: p<0.05; **: p<0.01; ***: p<0.001; ****: p <0.0001; Unpaired Student's t-test, mean±SD