Zinc adjuvant treatment in SARS-CoV-2: a randomized clinical trial

Abstract

Introduction: Zinc is a trace element with a key role in immune function and has demonstrated antiviral and anti-inflammatory properties. Low plasma zinc levels have been associated with poor outcomes in COVID-19. This study aims to evaluate the efficacy and safety of zinc supplementation as an adjuvant therapy in hospitalized patients with COVID-19. Methods: A single-center, randomized, open-label clinical trial between May and December 2021. Adults hospitalized with confirmed COVID-19 requiring hospitalization were randomized 1:1 to receive standard of care (SoC) with or without oral zinc acetate (90 mg/day) for 14 days. The primary endpoint was disease progression, defined as critical care requirement (ICU admission) or death. Secondary outcomes included time to clinical recovery, hospital length of stay, WHO clinical scale improvement, inflammatory markers, antibody response, and safety. Results: Seventy-one patients were randomized (35 zinc versus 34 SoC). Disease progression occurred in 5.7 % of the zinc group versus 23.5 % in the SoC group (OR 0.21, 95 %CI = 0.03-0.96,). Mean recovery time was significantly shorter in the zinc group (7.4 ± 6.1 versus 13.1 ± 9.7 days, p = 0.006) and a trend to a faster recovery was observed in the Cox proportional hazards model in the intervention group HR of 1.670 (95 % CI: 0.948-2.942), p = 0.076. WHO scale improvement attaining a < 1 points at day 14 was greater in the zinc group (74.3 % versus 42.4 %, p = 0.009). Antibody levels were higher in the SoC group at days 14 and 28. No adverse events were attributed to zinc. Conclusions: Adjunctive zinc supplementation to standard of care reduced disease progression and showed a trend to accelerated clinical recovery in hospitalized COVID-19 patients, supporting the potential role of zinc in managing viral respiratory infections. Trial registration: ClinicalTrials.gov identifier, NCT05778383.

RV: Grant PID2022-136511OB-I00 funded by MICIU/AEI/10.13039/501100011033 and ERDF/EU; "Unidad de Excelencia María de Maeztu" CEX2024-001431-M, funded by MICIU/AEI/10.13039/501100011033. SG-Z: Grant FIS PI21/00509, funded by Instituto de Salud Carlos III (ISCIII), co-funded by the European Union and research grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). RGF: FIS PI23/00456 funded by Instituto de Salud Carlos III (ISCIII), co-funded by the European Union.