Melatonin, vitamins and minerals supplements for the treatment of Covid-19 and Covid-like illness: A prospective, randomized, double-blind multicenter study

•Melatonin, zinc and multivitamins were ones of the most recommended supplements for coronavirus disease 2019.•Melatonin only may be not enough to treat patients infected with Sars-Cov2, in a multicenter retrospective observational study involving 58 562 adult patients hospitalized for COVID-19, melatonin use (N = 272) at a mean daily dose of 2.6 mg was not associated with reduced mortality.•This is a multicenter prospective, randomized, double-blind, controlled trial to examine the efficacy and safety of the association. Melatonin, zinc, and multivitamins are among most recommended supplements in the fight against coronavirus disease 2019 (COVID-19). We aimed to examine the efficacy and safety of this association in the treatment of COVID-19 and COVID-like illnesses. We conducted a multicenter prospective, randomized, double-blind, controlled trial. Patients with no medical history consulting the emergency department for covid and covid-like illness and who were not hospitalized were included. Patients were assigned in a 1:1 ratio to the treatment or the placebo group. The primary outcome was studying the effectiveness of zinc multivitamin supplement and melatonin in the treatment of COVID and -like illnesses symptoms’ according to the time from randomization to clinical improvement. The pre-specified secondary outcomes were date of disappearance of symptoms present on admission, appearance of an adverse effect due to the administration of the treatment, number of patients developing complications, requiring hospitalization, requiring respiratory support. One hundred sixty four patients were eligible for the study and were randomized to either the treatment group or the placebo group. Overall, 128 of the 164 patients had a PCR for SARS-CoV-2, yielding a positive PCR result in 49.1% of them. Regarding the disappearance of all initial presenting symptoms: on the 5th day of the follow-up, there was a significant difference between the two groups with a p value 0.04;On the 10th day, there was a significant difference too with p value of 0.038. There were no significant differences between the two groups in recovery during the 15th day of follow-up p>0.5. Finally, 100% of patients fully recovered in the treatment group vs 98.8% in the placebo group. No severe adverse events were reported throughout the trial. Our results showed that daily doses of Melatonin, zinc and vitamins did significantly reduce the duration of symptoms accelerating its disappearance amon