From Clinical Trials to Communities: an observational study to evaluate the efficacy of Antiviral Therapies for Severe Acute Respiratory Syndrome Coronavirus 2 infections within Wales

Abstract

Background and Purpose. The COVID-19 pandemic of SARS-CoV-2 poses significant health risks, namely respiratory and immune-related symptoms, which can lead to hospitalisation or death. Several antiviral drugs have undergone clinical trials with mixed results, but ultimately Paxlovid, molnupiravir, and sotrovimab have been approved by the UK's medicines regulatory agency. This study aims to evaluate their effectiveness in the Welsh community, as their efficacy outside of clinical trials remains uncertain.

Experimental approach. Using a retrospective cohort design, this study was conducted in Wales to evaluate the efficacy of antiviral drugs in high-risk (see Appendix A) non-hospitalised COVID-19 patients. These patients were retrospectively monitored for 28 days examining for the primary endpoints of hospitalisation and mortality. Confirmation of antiviral prescription was obtained from the National Antiviral Service Cymru. From this, digital copies of patients’ notes were reviewed online for evidence of hospitalisation or death. Ethical approval was not required since no further clinical testing was involved. Data handling was congruous with the Cardiff and Vale University Health Board policies.

Key Results. The primary study included 820 total patients, with a male-to-female ratio of 41:59 and a median age of 60. Overall analysis identified that 6.2% of all patients (N=820) met the criteria for a primary endpoint within the 28-day window. The combined mean primary endpoint rates for all drugs between the primary study (6.2%) and pivotal trials (1.9%) did not differ, p = 0.24.

There was no statistical difference between the incidence in the Molnupiravir treatment group (8.2%) and its respective pivotal clinical trial (8.2%), p = 0.27. Sotrovimab displayed a significantly higher primary endpoint rate of 2.6% when compared to the pivotal trial result of 1.1%. This decrease in efficacy since market authorisation was statistically significant to p = 0.04.

Conclusion. COVID-19 antiviral treatment with Paxlovid, molnupiravir, or sotrovimab reduced the risk of hospitalisation or death in high-risk non-hospitalized patients. However, the efficacy of these drugs in the community setting appears lower than in pivotal clinical trials. The reasoning behind this is not clear, although it may be due to SARS-CoV-2 mutations or the UK vaccination program. Specifically, a higher incidence rate was found within the sotrovimab treatment group than the clinical trial. Further research across a larger UK-wide patient population is needed to confirm the true effect of COVID-19 antiviral drugs in the community.