(A) C57BL/6J wild-type (WT) and rag−/− mice were intranasally infected with 1 × 105 PFU/mouse SARS-CoV-2 MA10 and weighed daily. Animals were euthanized at day 3, 7, or 14 after infection and lungs were collected for histology, qPCR, and flow cytometry analysis. (B) Weight change of 3-month-old WT and rag−/− mice following infection. n = 6 for each strain; the experiment was performed once. Two-way ANOVA with Bonferroni’s multiple comparisons test. (C) Weight change of 6-month-old WT and rag−/− mice following infection with 104 and 105 PFU SARS-CoV-2 MA10. WT: n = 6, rag−/−: n = 3 (104 PFU), WT: n = 7, rag−/−: n = 2 (105 PFU); the experiment was performed once. Two-way ANOVA with Tukey’s multiple comparisons test. (D) Weight change of 6-month-old WT and rag−/− mice following infection with 105 PFU SARS-CoV-2 MA10. WT: n = 19, rag−/−: n = 24; the experiment was performed three times. Two-way ANOVA with Bonferroni’s multiple comparisons test. (E) Lung viral RNA levels at days 3, 7, and 14 after infection in WT and rag−/− mice. Day 3 WT: n = 7, rag−/−: n = 10; day 7 WT: n = 8, rag−/−: n = 7; day 14 WT: n = 4, rag−/−: n = 5; the experiment was performed three times. Two-way ANOVA with Tukey’s multiple comparisons test. (F) H&E staining (top row) of WT and rag−/− mice and immunohistochemistry staining (brown stain, bottom row) against the SARS-CoV-2 MA10 nucleoprotein at day 3 after infection. Experiment was performed once. (G) Histological scoring of WT and rag−/− mice lungs at day 3 after infection. WT: n = 3, rag−/−: n = 7; the experiment was performed once. Mann-Whitney U test.