Zinc supplementation as an adjunct therapy for COVID‐19: Challenges and opportunities

Abstract

An outbreak of a novel coronavirus (COVID-19 or 2019-CoV) infection has posed significant threats to international health and the economy. Patients with COVID-19 are at risk of cytokine storm, acute respiratory distress syndrome (ARDS), reduced blood oxygenation, mechanical ventilation, and a high death rate. Although recent studies have shown remdesivir and dexamethasone as treatment options, there is an urgent need to find a treatment to inhibit virus replication and to control the progression of the disease. Essential biometal zinc has generated a lot of excitement as one of the promising candidates to reduce the severity of COVID-19 infection. Several published observations outlined in the review are the reasons why there is a global enthusiasm that zinc therapy could be a possible therapeutic option. However, the biggest challenge in realising the therapeutic value of zinc is lack of optimal treatment modalities such as dose, duration of zinc supplementation and the mode of delivery.In this review, we discuss the regulatory mechanism that hinges upon the bioavailability of zinc. Finally, we propose that intravenous zinc could circumvent the confounding factors affecting the bioavailability of zinc and allow zinc to achieve its therapeutic potential. If successful, due to advantages such as lack of toxicity, low cost and ease of availability, intravenous zinc could be rapidly implemented clinically.

The effect of circulating zinc, selenium, copper and vitamin K1on COVID-19 outcomes: a Mendelian randomization study

“…Zinc's many antiviral, immunomodulatory and anti-inflammatory functions have generated a lot of interest for its potential use in COVID-19 management (8,13,49,50,77). Consequently, over 50 RCTs including zinc, albeit typically used as adjuvant treatment or prophylactic, have commenced (ClinicalTrials.Gov, September 2021).…”

“…There, the initial hypozincemia and hyposelenemia is thought to stem from disease-driven inflammatory process (acute phase response), is found chiefly in plasma (but not e.g. erythrocytes) (13,89,90) and recovers over time in survivors. However, this does not mean that pre-existing deficiencies will not have a compounded negative impact at this stage (50).…”

“…Of relevance to COVID-19, zinc deficiency can lead to dysfunctional immune response with reduced activity of innate immune cells (6,7), lymphopenia (8) and activation of NF-KB signalling inducing production of IL-6 and other cytokines involved in "cytokine storm", characteristic of COVID-19 (9)(10)(11). Furthermore, zinc has manifold antiviral properties in vitro and in vivo (12,13). With respect to SARS-CoV, Zn combined with a ionophore was shown to inhibit its RNA polymerase and block virus replication in cell culture (14).…”

“…This is especially important as any observational studies linking nutrients levels to COVID-19 outcomes will be confounded by fact that COVID-19 at-risk groups (e.g. the elderly, high BMI individuals, diabetics(47)) have on average lower/suboptimal levels of many micronutrients (8,10,13,42,44,(48)(49)(50) and at the same time suffer from poorer COVID-19 outcomes. MR analyses can help to clarify the causal pathway in such cases.…”

The effect of zinc lozenge on pain, oedema, and trismus after impacted third molar surgery: A prospective randomized, double-blinded, placebo-controlled study

“…5 Zinc is a group IIb metal that is involved in diverse physiological processes such as growth, immune system modulation and tissue repair, and it acts as antiinflammatory agent and can promote wound healing. 6 Zinc has been shown to be effective in the prevention of oral mucositis, xerostomia, and pain associated with chemotherapy. 7 A recent oncologic study showed zinc lozenge, showing a significant reduction in the use of https://doi.org/10.18231/j.jds.2021.004 2320-7302/© 2021 Innovative Publication, All rights reserved.…”