Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial

Abstract

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.

The effect of zinc on the outcome of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials

“… 6 Overall, the findings of this RCT suggest the promising role of zinc in the treatment of patients with COVID-19. 6 However, previous RCT by Thomas et al reported that zinc could not significantly decrease the duration of symptoms and was early terminated for futility. 7 Similar, the RCT by Abd-Elsalam et al did not find the additional clinical benefit of zinc supplement.…”

“…Recently, one randomized controlled trial (RCT), which investigated the clinical efficacy of zinc supplement for patients with COVID-19. 6 Ben Abdallash et al found that compared with placebo, treatment with oral zinc was associated with a lower 30-day mortality, ICU admission rate and shorter duration of symptoms and length of hospital stay. 6 Overall, the findings of this RCT suggest the promising role of zinc in the treatment of patients with COVID-19.…”

“… 6 Ben Abdallash et al found that compared with placebo, treatment with oral zinc was associated with a lower 30-day mortality, ICU admission rate and shorter duration of symptoms and length of hospital stay. 6 Overall, the findings of this RCT suggest the promising role of zinc in the treatment of patients with COVID-19. 6 However, previous RCT by Thomas et al reported that zinc could not significantly decrease the duration of symptoms and was early terminated for futility.…”

“…Four RCTs 6 , 7 , 8 , 9 were identified ( Table 1 ). Except one was a single-center phase 2 study, 9 all the other three were multicenter trials.…”

A Potential Role for Zinc to Enhance Treatment for Coronavirus Disease 2019 (COVID-19)?

“…For these reasons, the well-designed and executed study published in this issue of Clinical Infectious Diseases by Abdallah et al [8] represents an important methodological advancement. This carefully designed trial with recruitment of a much larger population compared with the few previous trials was therefore able to achieve a considerably higher statistical precision of the effect estimates, in addition to performing a careful randomization of the participants and blinding of both study subjects and investigators.…”