Antiviral Clinical Trials
A large number of clinical trials using experimental antiviral drugs are currently underway. A small proportion of them are aimed at repurposing existing antivirals, including arbidol (umifenovir), a broad-spectrum antiviral that blocks viral fusion; lopinavir/ritonavir (LPV/r), a combination of anti-HIV protease inhibitors; favipiravir, an RdRp inhibitor used to treat severe influenza infections (Hayden and Shindo, 2019); and remdesivir (Figure 6A). Chen et al. conducted a multicenter, randomized priority trial on 240 patients with confirmed COVID-19 infection to test favipiravir or arbidol (Chen et al., 2020b). Favipiravir was suggested to significantly improve symptom relief. However, the interpretation of this study is limited by a short clinical recovery window of 7 days, only 100 of 236 patients with confirmed COVID-19, and the lack of a control group.
LPV/r has previously shown efficacy in treating SARS-Cov-1 (Chu et al., 2004), prompting an early SARS-Cov-2 clinical trial (Li et al., 2020c). 44 patients were enrolled in a trial investigating the efficacy and safety of LPV/r (n = 21 patients), arbidol (n = 16), or control (n = 7) as treatment for mild to moderate COVID-19. At day 14 of treatment, 76.2%, 62.4%, and 71.4% of patients had a positive to negative conversion in the LPV/r, arbidol, and control groups, respectively, with no statistical significance between groups. A randomized controlled trial (RCT) with 200 severe COVID-19 patients did not observe a significant benefit of LPV/r either (Cao et al., 2020a). However, a study that looked at the impact of earlier administration of LPV/r treatment showed that when treatment of LPV/r was started within 10 days of symptom onset, a shorter duration of virus shedding was observed. Thus, timing of LPV/r administration may be critical to its efficacy (Yan et al., 2020a).
In a multicenter clinical study assessing the compassionate use of remdesivir in severe COVID-19 patients, 53 patients across several countries were treated with remdesivir for 10 days (Grein et al., 2020). 68% of the 53 patients who received remdesivir showed clinical improvement assessed through improved oxygen support or extubations. Without a proper control group, limited conclusions can be drawn with regards to the efficacy of remdesivir from this study. The measured 68% clinical improvement may be in line with average clinical improvement across patients treated with standard of care (Li et al., 2020c). A small RCT in China with 237 severe COVID-19 patients randomized 2:1 to remdesivir versus placebo demonstrated no significant benefit in time to clinical improvement (Wang et al., 2020g). Almost simultaneously, preliminary results from a larger National Institute of Allergy and Infectious Diseases (NIAID) RCT with more than 1,000 patients were announced with remdesevir to be associated with quicker time to recovery: 11 days compared with 15 days (Ledford, 2020). A non-significant benefit in mortality was also noted, and the trial was stopped early to allow access to remdesivir in the placebo arm. Complete safety data and full publication are awaited, but this study offers encouraging results and has resulted in an FDA emergency use authorization for remdesivir in hospitalized COVID-19 patients.