The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

Abstract

During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.

Keywords: 2019-nCoV; COVID-19; SARS-CoV2; coronaviridae; impaired immune system; zinc; zinc deficiency.

Figure 1

Viral mechanism of COVID-19 and how they might be opposed by zinc data. (1) There is an impressive intersection of known risk factors for zinc deficiency (blue circle) and the predisposition for a severe COVID-19 infection (red circle). (2,3) Zinc (Zn) supplementation might already prevent the viral entry and also suppresses its replication, while it supports the anti-viral response of the host cells. (4) As zinc is known to increase ciliary length and movements and also sustains tissue integrity, entrance of the virus is impeded. (5−10) The importance of zinc on the development and function of the immune cells is manifold. It should be underlined, that zinc's effects should not generally be described as activating or inhibiting, as zinc in various cases normalizes overshooting immune reactions and balances the ratios of the various immune cell types. Zinc thus prevents for example that high levels of inflammatory mediators including reactive oxygen and nitrogen species destroy the host tissue. (11) On first view it appears contradicting, that zinc increases activation induced production of reactive oxygen species in platelets, while it is generally considered as anti-oxidative. However, in case of platelets, up to a certain threshold, ROS production is essential, as it can prevent the formation of platelet aggregates. In summary, zinc therefore might be able to prevent vascular complications observed in COVID-19 patients. Details for each point can be found in the text. ACE2, angiotensin converting enzyme 2; AG, antigen; IFN, interferon; IFNR, interferon receptor; ISRE, interferon-sensitive response element; APC, antigen presenting cell; IKK, IκB kinase; IL, interleukin; iNOS, inducible nitric oxide synthase; IRF3, IFN regulatory factor 3; MHC, major histocompatibility complex; MEK1/2, mitogen-activated protein kinase kinase 1/2; NADPH oxidase, nicotinamide adenine dinucleotide phosphate oxidase; NFAT, nuclear factor of activated T-cells; NF-κB, nuclear factor kappa B; PKR, protein kinase R; Akt, protein kinase B; PI3K, phosphatidylinositol-3 kinases; ROS, reactive oxygen species; RdRP, RNA-dependent RNA polymerase; RNase L, ribonuclease L; Sirt-, Sirtuin 1; STAT, signal transducer and activators of transcription; TCR, T cell receptor; Tc, cytotoxic T cell; TH, helper T cell; TGF, transforming growth factor; TRAM, TRIF-related adaptor molecule; TRIF, TIR-domain-containing adapter-inducing interferon-β; TLR, toll-like receptor; TNF, tumor necrosis factor; Zip, Zrt- and Irt-like protein; ZO-1, zona occludens.