BACKGROUND Zinc supplementation has been considered one of the potential therapies for coronavirus disease-19 (COVID-19). We aimed to examine zinc efficacy in adult patients with COVID-19 infection. METHODS We conducted a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Patients tested positive for COVID-19 without end organ failure were randomized to oral zinc (n = 231) or matching placebo (n = 239) for 15 days. The primary combined outcome was death due to COVID-19 or ICU admission within 30 days after randomization. Secondary outcomes included length of hospital stay for inpatients and duration of COVID-19 symptoms with COVID-19 related hospitalization for outpatients. FINDINGS One hundred ninety patients (40.4%) were ambulatory and 280 patients (59.6%) were hospitalized. Mortality at 30-day was 6.5% in Zinc group and 9.2% in Placebo group [odds ratio (OR) 0.70 (0.37-1.32)]; ICU admission rate was respectively 5.2% and 11.3% [OR 0.46 (0.23-0.88)]. Combined outcome was lower in zinc group compared to placebo group [OR 0.62 (0.38-0.99)]. Consistent results were observed in prespecified subgroups of patients with age < 65 years, those with comorbidity, and those who needed oxygen therapy at baseline. Length of hospital stay was shorter in zinc group compared to placebo group [difference 3.5 days, 95% CI (2.76-4.23)] in inpatients group; duration of COVID-19 symptoms decreased with zinc treatment compared to placebo in outpatients [difference 1.9 days, 95% CI (0.62-2.6)]. No severe adverse events were observed during the study. INTERPRETATION Our results showed that in COVID-19 patients, oral zinc can decrease 30-day death and ICU admission rate and can shorten symptoms duration.

Intravenous MgSO appears to have a synergistic effect when combined with other AV nodal blockers resulting in improved rate control. Similar efficacy was observed with 4.5 and 9 g of MgSO but a dose of 9 g was associated with more side effects.

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