Zinc has a role in immunity, preventing inflammation, hemostasis, ACE 2 activity, and tissue response to hypoxia, and it also possesses antiviral activity. However, its role in preventing upper respiratory tract infections (RTIs) has been limited by differences in administration route and formulations, outdated information, low-quality evidence, and the withdrawal of published systematic reviews.

To address these concerns, researchers conducted a rapid systematic review and meta-analysis of randomized, controlled trials to evaluate the benefits and risks of zinc formulations compared with controls for the prevention or treatment of acute viral RTIs in adults.

Investigators searched 17 English and Chinese databases in April/May 2020 for randomized, controlled trials on zinc for RTIs (i.e., adults at risk of contracting a viral RTI, those who had had a laboratory-confirmed RTI, or those who had had nonspecific respiratory tract illness mainly caused by viral infections). They also reviewed the literature from April/May 2020 to August 2020 for studies on the use of zinc for COVID-19. Systematic reviews, nonrandomized studies of interventions, studies without a current group, data on adults with bacterial or nonviral respiratory infections, and zinc cointerventions were excluded.

Outcomes included the incidence of RTIs, symptomatic survival, composite symptom severity scores, health-related quality of life, and adverse events.

Upon review, 29 randomized, controlled trials including 5,446 participants met the inclusion criteria. All of the studies involving SAR-CoV-2 and zinc utilization were in progress, and there were no completed trials. The most common zinc preparations used were lozenges, followed by nasal sprays and gels containing either zinc acetate or gluconate salts. Prophylactic dosages of oral zinc for community-acquired infections were either 15 mg or 45 mg for 7 to 12 months, whereas dosages of topical zinc to prevent or treat community-acquired infections were 0.9 mg/day to 2.6 mg/day.

Investigators rated the certainty and quality of the evidence and the risk of bias. The GRADE criteria scoring was downgraded when evidence of uncertainty or poor quality was observed.

Among the findings from the prevention studies, oral or topical nasal zinc had moderate certainty/quality evidence for a 32% reduction in developing mild-to-moderate symptoms consistent with a viral RTI. Five RTIs per 100 person-months of zinc use were prevented (number needed-to-treat [NNT] = 20). There was no evidence of serious adverse events in the prophylaxis studies, although the levels of certainty and quality were low.

In the treatment studies, a clinically important reduction of more than 1 point in Day 3 symptom severity scores was found for sublingual and topical nasal zinc, but there was no difference in average daily symptom severity scores. However, these findings were of low certainty and quality.

If zinc sublingual or topical therapy was initiated during the first week of symptoms, patients were 1.8 times more likely to recover sooner than those on placebo, but the evidence was of low quality and certainty. If patients were treated with zinc, 19 more adults per 100 were less likely to remain symptomatic at the end of the first week, with an NNT of 5. Very low certainty and quality evidence showed that zinc reduced the mean duration of symptoms by 2 days.

Although no serious adverse events were associated with zinc, zinc use increased the risk of nonserious adverse events compared with placebo. These included nausea, gastrointestinal discomfort, mouth irritation, soreness, and taste aversion, with the last three events being associated with the sublingual lozenge formulation. Zinc lozenges were more likely than nasal sprays and gels to cause any type of nonserious adverse event.

This comprehensive rapid systematic review and meta-analysis provides useful information for pharmacists who frequently encounter patients seeking advice on the use of zinc during cold and flu season. Although the findings are encouraging, they are often based on low certainty or quality of evidence, so pharmacists should use their professional judgment when recommending zinc products.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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