Two different dual antibody treatments each reduce SARS-CoV-2 viral load by >0.5 log
Simon Collins, HIV i-Base
In one, early results were reported in JAMA from a randomised, placebo-controlled dose-ranging phase 2/3 study using bamlanivimab both as monotherapy and in combination with etesevimab. 
Both these monoclonal antibodies (also called LY-CoV555 and LT-CoV016 respectively) were derived from two patients with COVID-19 (in China and the US) and are in development with Eli Lilly.
The findings included a significant but small difference in the primary endpoint of reduction in viral load at day 11 for the combination arm compared to placebo, but no effect for the monotherapy arms.
The BLAZE-1 study included 577 participants with mild to moderate COVID-19 (with at least one symptom) at 49 trial sites in the US who received at least one randomised dose. In the initial stage, from 17 June to 21 August 2020, participants were randomised to one of three doses of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]) or placebo, with results already reported. 
From 22 August to 3 September participants were randomised to dual therapy (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]) vs placebo.
The final results (until 6 October), included a change in log viral load from baseline at day 11 was –3.72 for 700 mg, –4.08 for 2800 mg, –3.49 for 7000 mg, –4.37 for combination treatment, and –3.80 for placebo.
Only the combination therapy arm was significantly different compared to placebo: –0.57 (95%CI: –1.00 to –0.14], p=0.01.
Significant differences were also reported for 10 of the 84 secondary endpoints. These do not appear to follow a dose-related pattern, or even mono vs dual therapy trend and it is unclear whether the multiple comparisons were adjusted for.
An interim analyses of a second study published in NEJM, with a combination of two neutralising IgG1 antibodies, also reported a similar impact on SARS-CoV-2 viral load: –0.56 log copies/mL at day 7 (in participants who were antibody negative at baseline). 
Although the dual combination significantly reduced SARS-CoV-2 viral load, it is unclear whether an approximate half log reduction in viral load will have clinical significance.
Some clinical benefits were reported for the pooled active vs placebo analysis in the first phase of the study, although these were in post hoc analyses. 
However, it is interesting that a similar viral load effect was associated with reduced hospital visits and admission with the Regn-CoV-2 dual antibody.
An editorial in NEJM from Mike Cohen commented on the higher risk of serious hospitalisation correlated with very high viral load and this might be limited by early antibody treatment or by a rapid autologous immune responses. 
Also, that combination monoclonal antibodies might have a protective role in people who need more rapid protection than offered by a vaccine.
No benefits are seen with these compounds in later infecftion perhaps because inflammation and coagulopathy play a greater role than viral replication.
A recent useful webinar sponsored by multiple organisations (including the Indian government, Wellcome and IAVI) is now online about global access to monoclonal antibodies. 
- Gottlieb RL et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA. DOI:10.1001/jama.2021.0202. (21 January 2021).
- Chen P et al; for the BLAZE-1 Investigators. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med. DOI:10.1056/NEJMoa2029849. (28 October 2020).
- Weinreich DM et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med 2021; 384:238-251. DOI: 10.1056/NEJMoa2035002. (21 January 2021).
Cohen MS et al. Monoclonal antibodies to disrupt progression of early Covid-19 infection. Editorial comment. NEJM 2021; 384:289-291. DOI: 10.1056/NEJMe2034495. (21 January 2021).
- Global access pathways for monoclonal antibodies: Can Covid-19 pave the way? (19 January 2021).