N-dihydrogalactochitosan reduces histopathology associated with SARS-CoV-2 infection in lungs.

Lungs from hACE2 transgenic mice were collected at the time of death, thin sectioned, and hematoxylin and eosin stained for histopathological scoring. Images show representative lungs. (a) Normal lung from a PBS-treated, mock inoculated mouse at day 14. Bronchioles lined by epithelial cells, alveolar septa containing pulmonary capillaries lined by pneumocytes, and a small arteriole are visible (inset). (b) Lung from a GC + 103 PFU SARS-CoV-2 mouse at day 7 with patchy inflammation (black arrows) distributed around airways and affecting approximately 15% of the section. Peribronchiolar alveolar septal inflammation composed primarily of lymphocytes and macrophages (asterisk, inset) with scattered multinucleated cells. (c) Lung from a PBS + 103 PFU SARS-CoV-2 inoculated mouse at day 7 showing widespread, multifocal to coalescing inflammation affecting all lung lobes and approximately 60% of the section. The inset shows lymphohistiocytic bronchoalveolar inflammation (asterisk) with multinucleated syncytial cells (circled), endotheliitis (black arrowheads) and bronchiolar epithelial hyperplasia characterized by disorganization and piling-up of bronchiolar epithelium with increased mitotic figures (black arrows). (d) Total affected lung area was estimated using image analysis software. (e-f) Lung lesion severity was scored according to criteria defined in S2 Table in S1 File. Scale bars are 2 mm (subgross) and 50 μm (insets). As = alveolar septa, B = bronchioles, Br = bronchus, BV = blood vessel. ** p p p F = 35.86, pF = 10.32, p<0.0001, 4 degrees of freedom (e). Symbols are individual animals, bars show the mean, and error bars show the standard deviation, n = 8–16 per group, 2 combined experiments.