Fig. 1: SARS-CoV-2 RNA and histopathology in rhesus macaques, baboons and marmosets.

a–d, vRNA in BAL fluid (a), NS (b) and RS (c) collected longitudinally, and lung tissue homogenates (d) collected at the end point (14–17 d.p.i.) from rhesus macaques infected with SARS-CoV-2. e–h, vRNA in BAL fluid (e), NS (f) and RS (g) collected longitudinally, and lung tissue homogenates (h) at the end point (14–17 d.p.i.) from baboons infected with SARS-CoV-2. n = 12. i–l, Comparison of vRNA in BAL fluid (i), NS (j), RS (k) and lungs (l) of rhesus macaques and baboons infected with SARS-CoV-2. m,n, To estimate the persistence of replicative virus, we performed subgenomic RNA estimation on end-point lung samples of rhesus macaques (m) and baboons (n). n = 12. o,p, vRNA in nasal wash (o) and oral (p) longitudinal swabs. n = 6 (0–3 d.p.i.) and n = 4 (6–14 d.p.i.). q, vRNA was also measured in lung homogenates of marmosets at the end point. n = 2 (3 d.p.i.) and n = 4 (14 d.p.i.). Statistical analysis was performed using one-way (a–c and e–g) and two-way (i–k) repeated-measures analysis of variance (ANOVA) with Geisser–Greenhouse correction for sphericity and Tukey post hoc correction for multiple testing (GraphPad Prism 8). r, Histopathological analysis in infected rhesus macaques revealed regionally extensive interstitial lymphocytes, plasma cells, lesser macrophages and eosinophils expanding the alveolar septa (bracket) and alveolar spaces filled with macrophages (asterisks). The normal alveolar wall is indicated (arrow) for comparison (top). Bottom, alveolar spaces with extensive interstitial alveolar wall thickening by deposits of collagen (asterisks) and scattered alveolar macrophages (arrow). s, Histopathological analysis in infected baboons also revealed regionally extensive interstitial lymphocytes, plasma cells, lesser macrophages and eosinophils expanding the alveolar septa (bracket) and alveolar spaces filled with macrophages (asterisk) (top). Bottom, alveolar wall thickening by interstitial deposits of collagen (asterisk), alveoli lined by occasional type-II pneumocytes (arrowheads) and alveolar spaces containing syncytial cells (arrows) and alveolar macrophages. t, Histopathological analysis in marmosets revealed a milder form of interstitial lymphocytes, and macrophages recruited to the alveolar space. Scale bars, 100 μm (r, s (top), t (top)) and 50 μm (s (bottom) and t (bottom)). u,v, Comparison of the lung inflammation score (u) and end-point viral titre (v) of infected rhesus macaques and baboons. n = 12. Statistical analysis was performed using one-tailed Mann–Whitney U-tests (m, n, u and v). For a–q, u and v, the shapes indicate old (triangles) and young (diamonds) rhesus macaques; old (inverted triangles) and young (squares) baboons; and old marmosets (hexagons). The different colours represent individual animals (Supplementary Table 1). For a, b, e–g, i–k, m–o, u and v, P values are indicated above the plots. Data are mean (i, k and q) or mean ± s.e.m. (a–h, m–o, u and v).