4. Discussion
ill, SARS-CoV-2 infections
ADVERSE EVENTS, SARS-COV-2 INFECTION, INFLUENZA
In this phase 2 dose-range finding study, probenecid was associated with a potent, dose-dependent antiviral effect and a significant reduction in COVID-19-related symptoms in non-hospitalized patients who were mildly to moderately symptomatic with COVID-19. Considerable antiviral activity was observed, with a significant reduction in the time required to reach an undetectable SARS-CoV-2 viral load and a significant difference in the change from baseline in SARS-CoV-2 viral RNA concentrations. There was a significant reduction in all COVID-19-related symptoms associated with probenecid versus placebo treatment.Treatment with probenecid was generally safe and well tolerated, with only mild adverse events noted. Probenecid has been marketed since 1951 and has been used safely by millions of patients across the globe [The significance of OAT3 in viral replication was previously shown by the probenecid treatment of influenza, RSV, and SARS-CoV-2 infections [Probenecid is relatively easy to manufacture and transport and has a long shelf-life [There are limitations to this clinical study. Specifically, the study participants were all enrolled in a single center in India, and viral genetic assessments were not performed. However, published reports indicated that the prevalent circulating SARS-CoV-2 variant at the time of enrollment in the area was the Omicron variant BA.2.75 (23.03%), followed by BA.2.38 (21.01%), BA.5 (9.70%), BA.2 (9.09%), BA.2.74 (8.89%), and BA.2.76 (5.56%) [In conclusion, treatment with probenecid was associated with a significant, dose-related decrease in the time to viral clearance and a significant increase in the proportion of patients with complete symptom resolution by day 10. Both dose levels of probenecid which were tested were generally safe and well tolerated. Based on these results, probenecid 1000 mg b.i.d. for five days will be further evaluated to characterize its efficacy in patients with COVID-19. Future studies will explore the efficacy of probenecid in more severely ill patients as well as those > 65 years of age.