Evaluation of the Efficacy of Methylene Blue Administration in SARS-CoV-2-Affected Patients: A Proof-of-Concept Phase 2, Randomized, Placebo-Controlled, Single-Blind Clinical Trial

Abstract

The SARS-CoV-2 pandemic has revolutionized the scientific and medical world in recent years. Methylene blue (MB) is a well-known molecule. The aim of our study was to assess the efficacy of MB against early-phase SARS-CoV-2 infections. All patients with a positive swab for SARS-CoV-2 were eligible for the trial. The intervention was a starting dose of 200 mg MB or placebo in the morning and 100 mg in the evening on the first day and afterwards the standard daily dose of 200 mg. Patients were followed up for safety and efficacy until day 84. We analyzed 21 patients for the safety profile and 19 for the efficacy objective: of these, there were 11 in the MB group and 8 in the placebo one. In both groups, patients had undetectable RNA from day 3 and 10 out of 11 subjects in the MB group were virus free by day 12 vs. 6 out of 8 in the placebo one. None of the patients experienced serious adverse events. MB has proved to be a safe and well-tolerated drug. We did not find superiority of efficacy or viral clearance of MB compared to the placebo. Given the good in vitro efficacy, larger studies are needed to assess MB efficacy against COVID-19 in vivo.