ABSTRACT
Introduction: This living rapid review aims to systematically update evidence from randomised controlled trials (RCTs) on the efficacy and safety of any zinc formulation or dose compared to any control, for preventing or treating SARS-CoV-2 and other acute viral respiratory tract infections (RTIs) in adults. Methods: Protocol registration was 27-April-2020 (PROSPERO: CRD42020182044). Eight databases (one Chinese), four clinical trial registries (one Chinese) and two pre-print servers were then searched with no language or date restrictions. Post-protocol/pre-data extraction, the inclusion criteria was restricted to adults. Meta-analysis used weighted, random-effects models. Cochrane RoB 2.0 tool and GRADE were used to appraise evidence certainty. Searches for COVID-19 evidence are updated 6-monthly. Results: As of Oct-2020, 1,907 articles and protocols were screened, and 28 RCTs involving 5,403 participants (none with SARS-CoV-2 infections) were included. Compared to placebo, oral or intranasal zinc prevented 5 RTIs/100 person-months (95%CI: 1-9, NTT=20) in adults without zinc deficiency (moderate-certainty), but not pre/post exposure prevention following human rhinovirus inoculation (RR 0.96, 95%CI: 0.77-1.21, moderate-certainty). There was low-certainty evidence of clinically important RTI treatment outcomes. Compared to placebo, sublingual or intranasal zinc improved day-3 symptom severity (MD 1.2 points lower, 95%CI: 0.7-1.7) and reduced symptom duration (MD 2 days shorter, 95%CI: 0.2-3.5;HR 0.55 over 7-days, 95% CI: 0.32-0.91, NNT=5). There was an increased risk of non-serious adverse events (e.g. nausea, or mouth or nasal irritation) (ARR 14/100 adults, 95%CI: 4-16, NNH=7). In the 25 RCTs that reported adverse events, none were serious, including copper deficiency or anosmia. The April-2021 update search identified, four COVID-19 RCTs with 572 participants and 7 registered RCTs. These results will be included in the next update. Conclusion: Preliminary evidence suggests there may be a role for zinc in the COVID-19 pandemic. Further research and regular updating of the evidence is warranted. Keywords: Zinc, Complementary medicine, Common cold, Respiratory infections, Viral infections, COVID-19