Fig. 7: Therapeutic efficacy of C5 Trimer in Syrian hamster model.

a Golden Syrian hamsters (n = 6 biologically independent animals per group) were infected intranasally with SARS-CoV-2 strain LIV (PANGO lineage B; 10⁴ pfu). Individual cohorts were treated either 2 h pre-infection or 24 h post-infection (hpi) with 100 μl of C5 either intranasally (IN) or intraperitoneally (IP) as indicated or sham-infected with PBS. b Animals were monitored for weight loss at indicated time-points. Data are the mean value (n = 6) ± SEM. Comparisons were made using a repeated-measures two-way ANOVA with Geisser-Greenhouse’s correction and Šídák’s multiple comparisons test; at day 7: PBS vs. 4 mg/kg 2 h pre-inf i/n; ****P < 0.0001, PBS vs. 4 mg/kg 24 hpi i/n; ***P = 0.0005, PBS vs. 4 mg/kg 24 hpi i/p; ***P = 0.0002, PBS vs. 0.4 mg/kg 24 hpi i/n; ***P = 0.0003. c RNA extracted from lungs was analysed for SARS-CoV-2 viral load using qRT-PCR for the N gene levels by qRT-PCR. Assays were normalised relative to levels of 18S RNA. Data for individual animals are shown with the median value represented by a horizontal line. Data are mean value (n = 6) ±SEM and were analysed using a Kruskal–Wallis one-way ANOVA with Dunn’s multiple comparisons test; PBS vs. 4 mg/kg 2 h pre-inf i/n; P = 0.1682 (ns), PBS vs. 4 mg/kg 24 hpi i/n; P > 0.9999 (ns), PBS vs. 4 mg/kg 24 hpi i/p; *P = 0.0287, PBS vs. 0.4 mg/kg 24 hpi i/n; P = 0.4044 (ns). d Morphometric analysis of HE-stained sections scanned and analysed using the software programme Visiopharm to quantify the area of non-aerated parenchyma and aerated parenchyma in relation to the total area. Results are expressed as the mean free airspace in lung sections. Data are mean value (n = 6) ±SEM and were analysed using a one-way ANOVA with Dunnett’s multiple comparisons test; PBS vs. 4 mg/kg 2 h pre-inf i/n; *P = 0.0109, PBS vs. 4 mg/kg 24 hpi i/n; *P = 0.0406, PBS vs. 4 mg/kg 24 hpi i/p; *P = 0.0270, PBS vs. 0.4 mg/kg 24 hpi i/n; *P = 0.0110. e Lung sections of hamsters, infected intranasally with 10⁴ PFU/100 μl SARS-CoV-2 and euthanized at day 7 post infection. Animals had been untreated prior to infection (PBS) or treated with 4 mg/kg C5 IN 2 h prae infection (h prae inf) or 24 h post infection (h post inf) or IP at 24 h post inf, or had received 0.4 mg/kg C5 IN at 24 h post inf. In the untreated animal (PBS) the lung parenchyma exhibits a large consolidated area (arrow) and multifocal patches with extensive viral antigen expression in particular by pneumocytes. In treated animals there are only a few small areas of consolidation (arrows). The animal treated with 4 mg/kg C5 intranasally at 2 h prae inf exhibits a few small patches with viral antigen expression mainly in degenerate cells, all other treated animals show viral antigen expression in occasional individual macrophages within small infiltrates or in pneumocytes in individual alveoli. Top: HE stain, bottom: immunohistology for SARS-CoV-2 N, hematoxylin counterstain. Bars = 20 µm (PBS) or 10 µm (all others). Images are representative n = 6 biologically independent samples.