Fig. 2.

Deficiency of C3 protects against severe COVID-19 in MA30-infected B6 mice. A–C and G–H: C3^−/− and C3^+/+ mice (n=9/group) aged 14 weeks and of mixed sex (5 males and 4 females per goup) were infected with a lethal dose of MA30 (5×10⁴ TCID₅₀) and sacrificed at 4–5 and 12 DPI. Percent body weight (A) and survival rate (B) after the infection were analyzed by Two-way ANOVA and survival by Log rank (Mantel-Cox) test. C Viral load was quantified by measuring subgenomic N RNA by qPCR in the mice at 4-5 DPI. D–F 9 C3^−/− and 9 C3^+/+ male mice were infected with MA30 5×10⁴ TCID₅₀ and were sacrificed at 3DPI for tissue collection. C3a (D) and C5a (E) serum levels as quantified by sandwich ELISA. Statistics show significance between groups using One-way ANOVA with Tukey’s multiple comparisons. Of note, there is a non-specific C3a signal in C3^-/- mice, which may be the result of sample hemolysis and non-specific binding. F Complement activity measured by hemolytic assay with exposure of serial dilution of sera from C3 sufficient and deficient mice at 3 DPI to antibody sensitized sheep erythrocytes. G–H Representative images (G) of edema from C3 sufficient and C3 deficient mice after infection at 4-5DPI, and quantification (H) by two-tailed student T-test. * p < 0.05, ** p < 0.01, ***p < 0.001, and **** p < 0.0001 by the respective statistical methods as detailed above