DOI QR코드

DOI QR Code

Clinical Effects of Zinc Supplementation in Patients Hospitalized with COVID-19: A Systematic Review and Meta-analysis

코로나바이러스감염증-19로 입원한 환자들에 대한 아연의 임상적 효과: 체계적 문헌고찰 및 메타분석

  • Received : 2021.05.13
  • Accepted : 2021.06.17
  • Published : 2021.06.30

Abstract

Background: Zinc is known for modulating antiviral and antibacterial immunity and regulating inflammatory response. This study aimed to examine the effect of zinc supplementation on clinical outcomes of hospitalized COVID-19 patients through systematic literature review and meta-analysis. Methods: PubMed/Medline, Embase, and Cochrane library databases were searched for studies comparing zinc supplement group versus control group for clinical outcomes of COVID-19 up to November 3, 2020. The search results were updated on February 9, 2021. The meta-analysis was performed by RevMan 5.4 software. Results: Total 4 studies were included in this systematic review. The zinc administered group had a significantly lower mortality rate compared with the control group (odds ratio [OR] 0.63, 95% confidence interval [95% CI] 0.53-0.75, p<0.001), with significantly higher discharge rate (OR 1.32, 95% Cl 1.15-1.52, p<0.001). However, there were no significant differences in the intensive care unit admission rate (OR 1.07, 95% Cl 0.26-4.48, p=0.92), mechanical ventilation rate (OR 0.80, 95% Cl 0.45-1.41, p=0.44), and length of hospital stay (mean difference 0.75, 95% Cl -0.64 to 2.13, p=0.29) between the two groups. Conclusion: The meta-analysis of zinc administration showed positive clinical effects on the discharge rate and mortality of COVID-19 hospitalized patients. However, large-scale randomized controlled trial should be conducted for zinc to be considered as one of the adjuvant treatments.

Keywords

References

  1. World Health Organization. Coronavirus disease (COVID-19) pandemic. Available from https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed November 24, 2020.
  2. Bimonte S, Crispo A, Amore A, Celentano E, Cuomo A, Cascella M. Potential antiviral drugs for SARS-Cov-2 treatment: Preclinical findings and ongoing clinical research. In Vivo 2020;34(3 Suppl):1597-1602. https://doi.org/10.21873/invivo.11949
  3. Prasad AS. Discovery of zinc for human health and biomarkers of zinc deficiency. Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals 2017;241-260.
  4. Gammoh NZ, Rink L. Zinc in infection and inflammation. Nutrients 2017;9(6):624. https://doi.org/10.3390/nu9060624
  5. Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients 2017;9(12):1286. https://doi.org/10.3390/nu9121286
  6. Acevedo-Murillo JA, Garcia Leon ML, Firo-Reyes V, Santiago-Cordova JL, Gonzalez-Rodriguez AP, Wong-Chew RM. Zinc supplementation promotes a Th1 response and improves clinical symptoms in fewer hours in children with pneumonia younger than 5 years old. a randomized controlled clinical trial. Front Pediatr 2019;7:431. https://doi.org/10.3389/fped.2019.00431
  7. Barnett JB, Hamer DH, Meydani SN. Low zinc status: a new risk factor for pneumonia in the elderly? Nutr Rev 2010;68(1):30-7. https://doi.org/10.1111/j.1753-4887.2009.00253.x
  8. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One 2014;9(10):e109180. https://doi.org/10.1371/journal.pone.0109180
  9. Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Adv Nutr 2019;10(4):696-710. https://doi.org/10.1093/advances/nmz013
  10. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 2010;6(11):e1001176. https://doi.org/10.1371/journal.ppat.1001176
  11. Awotiwon AA, Oduwole O, Sinha A, Okwundu CI. Zinc supplementation for the treatment of measles in children. Cochrane Database Syst Rev 2017;6(6):CD011177.
  12. Bobat R, Coovadia H, Stephen C, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial. Lancet 2005; 366(9500):1862-7. https://doi.org/10.1016/S0140-6736(05)67756-2
  13. Zeng L, Zhang L. Efficacy and safety of zinc supplementation for adults, children and pregnant women with HIV infection: systematic review. Trop Med Int Health 2011;16(12):1474-82. https://doi.org/10.1111/j.1365-3156.2011.02871.x
  14. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA GROUP. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535. https://doi.org/10.1136/bmj.b2535
  15. Higgins JP, Altman DG, Gotzsche PC, et al. The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. https://doi.org/10.1136/bmj.d5928
  16. Wells GA, Shea B, O'Connell Da, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.2011. Available from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed February 14, 2021.
  17. Lim SM, Shin ES, Lee SH, et al. Tools for assessing quality and risk of bias by levels of evidence. J Korean Med Assoc 2011; 54(4): 419-29. https://doi.org/10.5124/jkma.2011.54.4.419
  18. Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 2018;27(6):1785-1805. https://doi.org/10.1177/0962280216669183
  19. Higgins JPT TJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions version 6.1.0 [updated September 2020]. Available from www.training.cochrane.org/handbook. Accessed January 8, 2021.
  20. Yao JS, Paguio JA, Dee EC, et al. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest 2021;159(1):108-11. https://doi.org/10.1016/j.chest.2020.06.082
  21. Frontera JA, Rahimian JO, Yaghi S, et al. Treatment with zinc is associated with reduced in-hospital mortality among COVID-19 patients: a multi-center cohort study. Res Sq [Preprint] 2020:rs.3.rs-94509.
  22. Carlucci PM, Ahuja T, Petrilli C, Rajagopalan H, Jones S, Rahimian J. Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients. J Med Microbiol 2020;69(10):1228-34. https://doi.org/10.1099/jmm.0.001250
  23. Abd-Elsalam S, Soliman S, Esmail ES, et al. Do zinc supplements enhance the clinical efficacy of Hydroxychloroquine?: a randomized, multicenter trial. Biol Trace Elem Res 2020:1-5.
  24. Lassi ZS, Moin A, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 2016;12(12):CD005978.
  25. Gao YD, Ding M, Dong X, et al. Risk factors for severe and critically ill COVID-19 patients:a review. Allergy 2021;76(2):428-55. https://doi.org/10.1111/all.14657
  26. Shittu MO, Afolami OI. Improving the efficacy of chloroquine and hydroxychloroquine against SARS-CoV-2 may require zinc additives - a better synergy for future COVID-19 clinical trials. Infez Med 2020;28(2):192-97.
  27. Wang L, Song Y. Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: a meta-analysis of randomized, double-blind and placebo-controlled trials. Clin Respir J 2018;12(3):857-64. https://doi.org/10.1111/crj.12646
  28. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev 2013;(6):CD001364.
  29. Hemila H. Zinc lozenges may shorten the duration of colds: a systematic review. Open Respir Med J 2011;5:51-58. https://doi.org/10.2174/1874306401105010051

Cited by

  1. Rebalancing the unbalanced aged immune system – A special focus on zinc vol.74, 2022, https://doi.org/10.1016/j.arr.2021.101541