Antioxidant and Immune-Related Implications of Minerals in COVID-19: A Possibility for Disease Prevention and Management

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TL;DR

This narrative review examines the role of minerals—particularly zinc, selenium, copper, magnesium, and iron—in modulating immunity and oxidative stress in the context of COVID-19. The authors compile evidence from in vitro, observational, and clinical studies suggesting that adequate mineral status may support antiviral defense, reduce cytokine storm severity, and improve clinical outcomes. While supplementation shows promise as an adjuvant strategy, the authors emphasize the need for more well-designed clinical trials to confirm benefits and establish dosing guidelines.

Full summary

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**Background:** The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the need for adjunctive strategies beyond vaccination and antiviral treatments. Nutritional status, particularly mineral adequacy, is recognized as a modifiable factor influencing immune competence and oxidative stress regulation. This narrative review synthesizes evidence on the roles of zinc, selenium, copper, magnesium, iron, and other trace minerals in COVID-19 prevention and management.

**Methods:** A bibliographic search was conducted from January to March 2022 across Medline (PubMed), The Cochrane Library, Elsevier, and Dialnet, covering publications from 2019–2022. Keywords included COVID-19, SARS-CoV-2, minerals, trace elements, zinc, selenium, copper, iron, magnesium, nutrition, inflammation, and oxidative stress. Inclusion criteria encompassed randomized controlled trials, observational studies, meta-analyses, animal model, and in vitro studies published in English with open access. A total of 59 references were included and summarized in tabular form.

**Key Results:** - **Zinc:** Acts as a cofactor for ~3000 proteins including superoxide dismutase. It is essential for T cell maturation (via thymulin), NK cell activity, and regulation of cytokine production (reduces IL-6, IL-1β; stimulates IL-12). Zinc inhibits coronavirus RNA polymerase activity in vitro. Observational studies show COVID-19 patients are frequently zinc deficient, with deficiency associated with prolonged hospital stay and higher mortality. Clinical trials report that oral zinc (50 mg/day for 15 days) can reduce 30-day death, ICU admission, and symptom duration. However, some trials (e.g., Thomas et al. 2021) found no significant symptom reduction with high-dose zinc gluconate. - **Selenium:** Required for selenoprotein synthesis (GPX, TXNRD, selenoproteins P, K, W, S) which exert antioxidant, anti-inflammatory, and immunomodulatory effects. SARS-CoV-2 suppresses selenoprotein expression. The organoselenium compound ebselen shows strong inhibitory activity against SARS-CoV-2 M-pro and PL-pro proteases. Ecological data from China showed higher COVID-19 recovery rates in selenium-sufficient regions (Enshi cure rate 36.4% vs. 13.1% in other Hubei cities). A clinical trial found selenium administration restored lung antioxidant capacity in ARDS patients but did not significantly affect survival or ICU stay. - **Copper:** Cofactor for superoxide dismutase; supports monocyte, macrophage, neutrophil, and NK cell function. Copper ions rapidly inactivate human coronavirus 229E by genome destruction and envelope disintegration. Cu²⁺ blocks SARS-CoV-2 PL-pro in vitro. Copper deficiency is uncommon but associated with impaired immunity; excessive zinc intake can induce copper deficiency due to competitive absorption. - **Magnesium:** Cofactor for >600 enzymes; inhibits NF-κB activation via calcium-channel blocking, reducing IL-6 and TNFα production. Hypomagnesemia is prevalent in hospitalized COVID-19 patients and negatively correlated with infection severity and ICU stay. A clinical trial in older COVID-19 patients found that magnesium (150 mg/day) combined with vitamin D and B12 significantly reduced clinical deterioration requiring oxygen or ICU support. - **Iron:** Essential for immune cell function but also a redox catalyst that can generate hydroxyl radicals. COVID-19 disrupts iron metabolism: 90% of hospitalized patients in one study had low serum iron, while hyperferritinemia was common and associated with mortality. Iron overload may contribute to ferroptosis, ARDS, and pulmonary fibrosis. Iron chelators (e.g., deferoxamine) are proposed as potential treatments. - **Other minerals:** Sodium, potassium, and calcium levels are lower in severe COVID-19 and correlate with disease severity. Manganese activates IFN signaling and enhances CD8+ T cell memory. Iodine-based products (povidone-iodine) show virucidal activity. Lithium exhibits antiviral effects against coronaviruses in vitro.

**Clinical Implications:** The review supports the concept that maintaining adequate mineral status—through diet or targeted supplementation—may serve as a low-cost, safe adjuvant strategy for COVID-19 prophylaxis and management. Zinc and selenium show the strongest evidence for potential benefit, particularly in deficient populations. However, the authors caution against indiscriminate supplementation due to risks of toxicity (selenium, zinc), copper deficiency (excessive zinc), and iron overload. They recommend monitoring mineral status and call for more rigorous randomized controlled trials to establish definitive clinical guidelines.