Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial

Abstract

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

Assessing the antiviral potential of melatonin: A comprehensive systematic review

“…36 There was no statistically significant difference in the number of SARS-CoV-2 infections between the melatonin and placebo arms. 36 It is worth noting that the melatonin group showed a higher incidence of subjectively reported adverse events, including somnolence, in comparison to the placebo group. However, no severe adverse events related to treatment were reported during the study.…”

“…However, no severe adverse events related to treatment were reported during the study. 36 This trial is one of the few published investigations into melatonin's potential as a prophylactic treatment for SARS-CoV-2 infection. In this trial it is important to consider the limitations outlined in the study, as they may have led to the non-significant results.…”

Melatonin as a complementary and prophylactic agent against COVID‐19 in high‐risk populations: A narrative review of recent findings from clinical and preclinical studies

“…They concluded that the use of melatonin supplements could help reduce thrombosis, sepsis, and mortality in COVID19 patients [71]. In another study by García‐García et al [72] in which they evaluated melatonin's effect as a preventative measure against SARS‐CoV‐2 infection among healthcare workers at high risk of exposure to the virus in a randomized, double‐blind clinical trial. A total of 308 received the study treatment (148 placebo; 160 melatonin).…”

Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment

“…Further favorable effects of melatonin receptors in the COVID-19 context are their synchronizing effect on biological rhythms and their sleep-initiating properties that might be beneficial for intensive care patients suffering from disrupted sleep patterns or sleep deprivation, which favors the production of inflammatory cytokines and predisposition to lung inflammation [ 30 ]. First results from clinical trials on the effect of melatonin in critically ill patients with SARS-CoV-2 infection report a significantly improved clinical status when given as an adjunctive agent in combination with basic treatments in some studies but not in others without any apparent adverse events (Ref) [ [31] , [32] , [33] , [34] ].…”