Table 2.

Roles of trace elements and vitamin deficiency in worsening COVID-19 course and outcome

Trace element or vitamin	Deficiency and suggested role in COVID-19
Selenium
•Antioxidant role, ROS balance in inflammatory processes	•Immune function impairment, lower T cells, lymphocyte-mediated toxicity, and NK cell activity [234] •Increase in virus replication and genome mutation rate (especially for RNA viruses) [237] •Higher pathogenic H1N1 subtypes in influenza A virus [238] •Higher death rate in COVID-19 patients in low-selenium regions [240]
Zinc
•Reduces ROS in viral infections	•Higher risk for lower respiratory tract infections •Inhibition of RNA-dependent RNA polymerase, which inhibits viral replication in coronavirus respiratory tract infections [243] •Proposed supplementation to enhance the clinical of chloroquine/hydroxychloroquine efficacy in the COVID-19 treatment [246]
Copper
•Role in immunity, antimicrobial action due to copper toxicity •Enhance in macrophage activity in lung infection	•Immune function impairment •Role in viral replication in H1N1 influenza [255] •Proposed supplementation as an adjuvant within COVID-19 treatment [250]
Vitamin D
•Immunomodulatory and antioxidant action •Role in CVDs and DM	•Higher COVID-19 incidence in patients with lower vitamin D [264] •Higher COVID-19 fatality rate in severe vitamin D-deficient countries [265] •Proposed vitamin D at loading dose administration [266], [267], [268]
Ascorbic acid
•Immunomodulatory and antioxidant action	•Lower severity and mortality from pneumonia in individuals with higher serum vitamin C values [272,273] •Intravenous administration could reduce mechanical ventilation requirement through the amelioration of lung injury [274] •No consensus for supplementation in COVID-19, suggested 1.5 g/kg body weight administration as safe [275]
Vitamin A
•Role in immune competence •Immunomodulatory action	•Lower serum levels during infections (acute phase response), transiently and proportionally to the severity of the disease [280] •Lower FVC and higher risk for invasive pathogens and severity in lung infections in patients with lower vitamin A [278] •Suggested adjunctive administration in COVID-19 patients since reduced morbidity and mortality in measles‐related pneumonia, HIV infection, malaria [239]
Vitamin E
•Immunomodulatory and antioxidant action	•Supplementation as protective in upper respiratory infections in elderly patients [283] •Increased virulence as deficient in animal models [284] •Lack of available data for COVID-19 pandemic

CVD, cardiovascular disease; DM, diabetes mellitus; FVC, forced vital capacity; NK, natural killer; ROS, reactive oxygen species.

Numbers within brackets represent reference citation; see the Reference section.