Discussion
SARS, COVID-19 infection
VIRUS, ASYMPTOMATIC COVID-19, OTHER VIRAL INFECTION, COVID-19 INFECTION, INFLUENZA
These first data from the PLATCOV adaptive platform study show that ivermectin does not have a measurable antiviral effect in early symptomatic COVID-19 under our study methodology. In contrast, the preliminary results with casirivimab/imdevimab in patients infected with the SARS-CoV-2 Delta variant showed an approximate 50% acceleration in the viral clearance rate. This confirmed that the study methodology identifies efficiently those treatments which have clinically relevant antiviral effects in vivo. It remains uncertain whether any of the proposed, and often recommended, repurposed potential antiviral treatments have significant in vivo antiviral activity in COVID-19. This continued uncertainty, after 3 years of the pandemic, highlights the limitations of the tools currently used to assess antiviral activity in vivo. Clinically effective monoclonal antibodies and specific antiviral drugs have been developed. It is increasingly accepted that they are most effective early in the course of COVID-19 infection (The method of assessing antiviral activity in early COVID-19 reported here builds on extensive experience of antiviral pharmacodynamic assessments in other viral infections. It has the advantage of simplicity. It also avoids many of the limitations of unvalidated in vivo animal models (The quantitative relationship between the antiviral effect and clinical response varies, as host factors and viral virulence are both important determinants of outcome. However, many of the studies showing improved clinical outcomes did so in high-risk, unvaccinated, and previously uninfected adult patients with SARS CoV-2 virus variants which are no longer prevalent. The magnitude of the effects measured is sensitive to study design and to temporal and epidemiological influences (This trial has several limitations. It set a futility threshold of <12.5% acceleration of viral clearance, as currently available specific antiviral therapies provide approximately 30–50% acceleration (In summary, high-dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. This study provides no support for the continued use of ivermectin in COVID-19. Efficient characterization and comparison of potential antiviral therapeutics in COVID-19 will be important for policy recommendations, particularly while cost and availability limit access. Use of the rate of oropharyngeal viral clearance as a metric for antiviral efficacy has applicability beyond COVID-19 including other respiratory illnesses, notably influenza (