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. 2021 Sep 17;65(10):e01117-21. doi: 10.1128/AAC.01117-21

FIG 4.

FIG 4

Human equivalent dose of RDV in rhesus macaque models of COVID-19 or EBOV does not yield robust reductions in viral titers. (A and B) SARS-CoV-2-infected rhesus macaques (2.6 × 106 50% tissue culture infective doses [TCID50] of nCoV-WA1-2020) treated with the allometrically scaled dose of 10 mg/kg 1 dpi followed by 5 mg/kg 2 to 6 dpi yields a modest global reduction in SARS-CoV-2 viral titers. Data are adapted from the supplemental information in reference 11. (A) Heat map of organs profiled for the presence of SARS-CoV-2 RNA in RDV-treated (n = 6) and control (CT) (n = 6) animals. LN, lymph node; UL, upper lobe; ML, middle lobe; LL, lower lobe. (B) Viral loads in nose swabs and throat swabs between RDV-treated and CT animals. (C) No significant decrease in viral loads in the upper and lower respiratory tracts in patients treated with RDV (200 mg on day 1, 100 mg on days 2 to 10) was seen compared to placebo. Data are adapted from reference 2 and are presented as means (n = 107 [RDV] and 52 [placebo]). (D) Rhesus macaques were infected with EBOV (1,000 PFU; EBOV H. sapiens-tc/COD/1995/Kikwit) and treated i.v. with either 10 mg/kg RDV at 2 dpi for 12 days (light blue), a 10-mg/kg loading dose at 3 dpi and then 3 mg/kg for 11 days (dark purple), a 10-mg/kg loading dose at 3 dpi and then 3 mg/kg for 11 days (light purple), or vehicle (black). Animals (6 per group) were monitored for a total of 28 days. The most distinct reductions in viral titers occurred for NHPs in the 10-mg/kg treatment group (light blue). (E) Survival curves for NHPs at 28 dpi for treatment groups indicated. Though viral titers dropped to the limit of detection (LOD) for the 10/3-mg/kg D2 group (D, dark purple D) by day 12, only 2/6 NHPs in this group survived (E, dark purple), skewing viral titer data. At the same time, this reinforces the close relationship between stark reductions in viral titers and improved disease outcomes, as the remaining 2/6 animals in the 10/3-mg/kg D2 (2 days postinfection) group survived at 28 dpi. Data are adapted from reference 8.