Fig. 6: Accurate timing of corticosteroids is necessary to balance viral clearance and prevent immunopathology.

a, Weight change in dexamethasone-treated or control untreated mice during SARS-CoV-2 infection plotted as percent change compared to original weight before viral inoculation. Mice were treated with dexamethasone at 7, 8 and 9 dpi. Untreated n = 8 and treated n = 6 biologically independent mice examined over three independent experiments. Unpaired, two-tailed t-test determined comparing 14-dpi values (P = 0.0041). Means with s.d. are plotted. b, Human immune cells in 14-dpi lungs and BAL of MISTRG6-hACE2 mice treated with dexamethasone at 7, 8 and 9 dpi or left untreated. Untreated n = 8 and treated n = 6 biologically independent mice examined over three independent experiments. Unpaired, two-tailed t-test. Individual values for each mouse and means are plotted. c, Human immune lineages in 14 dpi-lungs of dexamethasone-treated or untreated mice within the human CD45⁺ population. Classical monocytes (CD14⁺), intermediate monocytes (CD14⁺CD16), non-classical monocytes (CD16⁺CD14⁻), macrophages (CD68⁺), NK cells (NKP46⁺), T cells (CD3⁺) and B cells (CD19⁺ and/or CD20⁺). MISTRG6-hACE2 mice were treated with dexamethasone at 7, 8 and 9 dpi. Unpaired, two-tailed t-test. Untreated n = 6 and treated n = 5 biologically independent mice examined over three independent experiments. Means with s.d. are plotted. d, Number of human macrophages in lungs of dexamethasone-treated and untreated mice at 14 dpi. Unpaired, two-tailed t-test. Untreated n = 8 and treated n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are plotted. e, Frequencies of alveolar or inflammatory macrophages in the lungs of MISTRG6-hACE2 mice that were treated with dexamethasone or left untreated. Unpaired, two-tailed t-test. Untreated n = 7 and treated n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are plotted. f, Numbers of alveolar or inflammatory macrophages in the lungs of MISTRG6-hACE2 mice that were treated with dexamethasone or left untreated. Unpaired, two-tailed t-test. Untreated n = 6 and treated n = 5 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are plotted. g, Frequencies (left) and numbers (right) of pDCs at 14 dpi in the lungs of dexamethasone-treated or control mice. Unpaired, two-tailed t-test. Untreated n = 5 and treated n = 4 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are plotted. h, Representative histograms for HLA-DR expression in lung T cells at 14 dpi in dexamethasone-treated or control mice. Unpaired, two-tailed t-test. Representative of n = 4 mice examined over two independent experiments. All attempts resulted in similar findings. i, Frequencies of HLA-DR⁺ or ICOS⁺ T cells at 14 dpi in the lungs and BAL of dexamethasone-treated or control mice. Unpaired, two-tailed t-test. Lung: untreated n = 5 and treated n = 4 biologically independent mice examined over three independent experiments. BAL: untreated n = 4 and treated n = 3 biologically independent mice examined over three independent experiments. Individual values for each mouse and means are plotted. j, Weight change in dexamethasone-treated or control mice during SARS-CoV-2 infection plotted as percent change compared to original weight before viral inoculation. Mice were treated with dexamethasone at 3, 4 and 5 dpi. Untreated n = 6 and treated n = 4 biologically independent mice examined over two independent experiments. Unpaired, two-tailed t-test. Means with s.d. are plotted. k, Human immune cells in lungs of MISTRG6-hACE2 mice treated with dexamethasone at 3, 4 and 5 dpi or left untreated (ctrl). n = 4 biologically independent mice examined over two independent experiments. Unpaired, two-tailed t-test. Individual values for each mouse and means are plotted. l, Viral RNA and viral titers measured by PFU in homogenized lung tissue at 7 dpi in dexamethasone-treated or control mice. n = 4 biologically independent mice examined over two independent experiments. Unpaired, two-tailed t-test. Individual values for each mouse and means are plotted. Mann–Whitney test, two-tailed. MISTRG6 mice were engrafted with CD34⁺ cells neonatally isolated from at least two donors. Pooled or infection matched representative results of at least two independent experiments are presented. Only P values <0.05 are plotted. Mean with s.d. or individual values are plotted. Dex, dexamethasone; Ctrl, control; NS, not significant.