Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients Open Access

Abstract

COVID-19 has rapidly emerged as a pandemic infection that has caused significant mortality and economic losses. Potential therapies and prophylaxis against COVID-19 are urgently needed to combat this novel infection. As a result of evidence suggesting zinc sulphate may be efficacious against COVID-19, our hospitals began using zinc sulphate as add-on therapy to hydroxychloroquine and azithromycin.

To compare outcomes among hospitalized COVID-19 patients ordered to receive hydroxychloroquine and azithromycin plus zinc sulphate versus hydroxychloroquine and azithromycin alone.

This was a retrospective observational study. Data was collected from medical records for all patients with admission dates ranging from 2 March 2020 through to 11 April 2020. Initial clinical characteristics on presentation, medications given during the hospitalization, and hospital outcomes were recorded. The study included patients admitted to any of four acute care NYU Langone Health Hospitals in New York City. Patients included were admitted to the hospital with at least one positive COVID-19 test and had completed their hospitalization. Patients were excluded from the study if they were never admitted to the hospital or if there was an order for other investigational therapies for COVID-19.

Patients taking zinc sulphate in addition to hydroxychloroquine and azithromycin (=411) and patients taking hydroxychloroquine and azithromycin alone (=521) did not differ in age, race, sex, tobacco use or relevant comorbidities. The addition of zinc sulphate did not impact the length of hospitalization, duration of ventilation or intensive care unit (ICU) duration. In univariate analyses, zinc sulphate increased the frequency of patients being discharged home, and decreased the need for ventilation, admission to the ICU and mortality or transfer to hospice for patients who were never admitted to the ICU. After adjusting for the time at which zinc sulphate was added to our protocol, an increased frequency of being discharged home (OR 1.53, 95 % CI 1.12–2.09) and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant (OR 0.449, 95 % CI 0.271–0.744).

This study provides the first evidence that zinc sulphate may play a role in therapeutic management for COVID-19.

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2020-09-15
2024-03-28
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References

  1. WHO Coronavirus disease 2019 (COVID-19) situation report; 2020; 46
  2. Huang C, Wang Y, Li X, Ren L, Zhao J et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395:497–506 [View Article]
    [Google Scholar]
  3. Yao X, Ye F, Zhang M et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020ciaa237
    [Google Scholar]
  4. Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 56:105949 [View Article]
    [Google Scholar]
  5. Magagnoli J, Narendran S, Pereira F, Cummings T, Hardin JW et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv 2020 [View Article][PubMed]
    [Google Scholar]
  6. Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect 2020; 50:384 [View Article][PubMed]
    [Google Scholar]
  7. Geleris J, Sun Y, Platt J, Zucker J, Baldwin M et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med 2020; 382:2411–2418 [View Article][PubMed]
    [Google Scholar]
  8. Maares M, Haase H. Zinc and immunity: an essential interrelation. Arch Biochem Biophys 2016; 611:58–65 [View Article][PubMed]
    [Google Scholar]
  9. Skalny AV, Rink L, Ajsuvakova OP, Aschner M, Gritsenko VA et al. Zinc and respiratory tract infections: perspectives for COVID‑19 (review). Int J Mol Med 2020; 46:17-26 [View Article][PubMed]
    [Google Scholar]
  10. Krenn BM, Gaudernak E, Holzer B, Lanke K, Van Kuppeveld FJM et al. Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections. J Virol 2009; 83:58–64 [View Article][PubMed]
    [Google Scholar]
  11. Hemilä H. Zinc lozenges may shorten the duration of colds: a systematic review. Open Respir Med J 2011; 5:51–58 [View Article][PubMed]
    [Google Scholar]
  12. Acevedo-Murillo JA, García León ML, Firo-Reyes V, Santiago-Cordova JL, Gonzalez-Rodriguez AP et al. 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 [View Article][PubMed]
    [Google Scholar]
  13. Barnett JB, Hamer DH, Meydani SN. Low zinc status: a new risk factor for pneumonia in the elderly?. Nutr Rev 2010; 68:30–37 [View Article][PubMed]
    [Google Scholar]
  14. te Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ et al. 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:e1001176 [View Article][PubMed]
    [Google Scholar]
  15. Xue J, Moyer A, Peng B, Wu J, Hannafon BN et al. Chloroquine is a zinc ionophore. PLoS One 2014; 9:e109180 [View Article][PubMed]
    [Google Scholar]
  16. Cao B, Wang Y, Wen D, Liu W, Wang J et al. A trial of Lopinavir-Ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; 382:1787–1799 [View Article][PubMed]
    [Google Scholar]
  17. Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe P. Enhancing immunity in viral infections, with special emphasis on COVID-19: a review. Diabetes Metab Syndr 2020; 14:367–382 [View Article][PubMed]
    [Google Scholar]
  18. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J Med Virol 2020; 92:479–490 [View Article][PubMed]
    [Google Scholar]
  19. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal 2020; 10:102–108 [View Article][PubMed]
    [Google Scholar]
  20. Science M, Johnstone J, Roth DE, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012; 184:E551–E561 [View Article][PubMed]
    [Google Scholar]
  21. Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in antiviral immunity. Adv Nutr 2019; 10:696–710 [View Article][PubMed]
    [Google Scholar]
  22. Faber C, Gabriel P, Ibs K-H, Rink L. Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response. Bone Marrow Transplant 2004; 33:1241–1246 [View Article][PubMed]
    [Google Scholar]
  23. Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med 2008; 14:353–357 [View Article][PubMed]
    [Google Scholar]
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