Fig. 5: Senolytic targeting mitigates disease features of COVID-19 in animal models and patients.

a, H3K9me3 IHA in nasopharyngeal (top) and lung (middle) specimens, and lipofuscin-based detection (bottom) of senescent cells in the lungs of golden hamsters infected with SARS-CoV-2 and treated with navitoclax or solvent-only (n = 5 animals each), or mock-infected and untreated (n = 3 animals) at day 7 after infection. b, H3K9me3 IHA and lipofuscin staining in nasopharyngeal sections of Roborovski dwarf hamsters infected with SARS-CoV-2 or mock at day 4 after infection and treatment as indicated. c, Lung tissue of dwarf hamsters as in b on day 4 after infection stained with haematoxylin and eosin. Uninfected healthy hamsters (mock) are shown for comparison ((xiv)–(xvii)). (i), (v) and (x) are overviews of lung sections. Signs of COVID-19-like pneumonia and haemorrhage are indicated: hyperplasia of the bronchial epithelium (double-headed arrows), haemorrhage (asterisks) and necrosis (black arrowheads) of alveolar epithelial cells with neutrophil infiltration (white arrowheads), and endothelialitis (black arrows). d, Quantification of the findings in c. *P < 0.05 by unpaired t-test (one-tailed). e, Multiplex bead-based protein analysis of dwarf hamster serum samples on day 4 after infection (as in b–d). n = 5 each (b–d; n = 4 each in e) for SARS-CoV-2-infected and treated (with solvent (Sol.) or navitoclax (Navito.) animals. n = 2 for healthy (mock) control. f, Constellation plots of patients with COVID-19 (ref. ⁵²) before (day 0) and after 7 days of standard care (SC) only or quercetin plus SC. Variables (Extended Data Table 2) were simultaneously analysed by agglomerative hierarchical clustering to visualize similarity (distance) between patients and separation of the cohorts after treatment. Multi-dimensional analysis of individual patient data, with each red or green dot indicating a patient, the line length represents the distance between patients, and axes showing arbitrary units. n = 21 for each group. All quantifications are mean ± s.d. Scale bars, 20 µm (c, middle two columns), 50 µm (a, b, c (right column)) or 1 mm (c, left column).