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[Preprint]. 2020 Dec 19:2020.12.10.20247205. [Version 4] doi: 10.1101/2020.12.10.20247205

Figure 3: Immune-targeting autoantibodies exacerbate disease in a mouse model of SARS-CoV-2 infection.

Figure 3:

K18-hACE2 mice were intranasally infected with 103 PFU (a,b) or 104 (c-g, h-l) PFU SARS-CoV-2. a, Body weight of PBS− (n = 10) or αIFNAR-treated (n = 8) K18-hACE2 mice from day 1 to 14 post infection measured as percent of body weight at day 0. b, Survival, defined as 10% weight loss, of PBS- (n = 10) or αIFNAR-treated (n = 8) K18-ACE2 from day 1 to 14. c,d, Relative frequency (c) and absolute number (d) of lung Ly6C+CD11b+CD64+ macrophages from mock-infected (n = 5), SARS-CoV-2-infected PBS-treated (n = 4), and SARS-CoV-2-infected αIFNAR-treated (n = 5) K18-ACE2 mice, e, Expression of CD64 on lung-infiltrating CD11b+Ly6Chigh monocytes from mock-infected (n = 5), SARS-CoV-2-infected PBS-treated (n = 4), and SARS-CoV-2-infected αIFNAR-treated (n = 5) K18-ACE2 mice. f-g, Relative frequency (f) and absolute number (g) of CD44+CD69+ lymphocytes (CD4+ T cells, CD8+ T cells, NK1.1+ cells, and γδ T cells) measured by flow cytometry. h, Body weight of PBS- (n = 5) or αIL-18-treated (n = 4) K18-hACE2 mice from day 1 to 14 post infection measured as percent of body weight at day 0. i, Survival, defined as 20% weight loss, of PBS- (n = 5) or αIL-18-treated (n = 4) K18-ACE2 from day 1 to 14. j, Viral burden from lung tissue homogenates measured 4 days post infection using RT-qPCR primer/probe sets against N or E genes from mock-infected (n = 5), SARS-CoV-2-infected PBS-treated (n = 5), and SARS-CoV-2-infected αIL-18-treated (n = 5) K18-ACE2 mice. k,l, Relative frequency (k) or absolute number (I) of CD11b+ and KLRG1+ NK1.1+ cells in lung tissues from mock-infected (n = 5), SARS-CoV-2-infected PBS-treated (n = 5), and SARS-CoV-2-infected αIL-18-treated (n = 5) K18-ACE2 mice. Significance was determined using two-way ANOVA followed by Sidak correction (a), Log-rank (Mantel-Cox) test (b), one-way ANOVA followed by Tukey correction (c-g, j), and unpaired two-tailed t test (k,l); *P < 0.05, **P < 0.01, ***P < 0.001, ****p < 0.0001. All error bars in this figure represent standard error of the mean.