Zinc
Zinc is considered a “guardian” for the body, as it plays an essential role in the functioning of the immune system [115], plays a central role in cell growth and differentiation of the immune system cells that have rapid differentiation and turnover [116]. Most of the studies have recently reported a very interesting evaluation of the function of zinc in antiviral immunity, suggesting how it can play a role in host defense against RNA viruses, inhibiting the RNA polymerase required by RNA viruses (such as coronaviruses) to replicate [117]. The zinc-binding metallothionein seems to play an important role in antiviral defense. Zinc deficiency has a marked impact on bone marrow, decreasing the number of immune precursor cells, with reduced output of naive B lymphocytes, and causes thymic atrophy, reducing the output of naive T lymphocytes. Therefore, zinc is essential for cell growth and differentiation of immune cells, helping to modulate the cytokine release and trigger CD8+ T cell proliferation.
Among the main activities of zinc in immune function there are: maintaining skin and mucosal integrity (e.g., cofactor for metalloenzymes required for cell membrane repair) [118]; improving the cytotoxic activity of NK cells [79, 82] and the phagocytic capacity of monocytes [64]. It is involved in the complement activity and in the production of IFN-γ [92, 95]; it is an important anti-inflammatory agent [119] and helps modulate the release of cytokines [95] by attenuating the development of pro-inflammatory Th17 and Th9 cells [64]. Furthermore, by influencing the generation of cytokines such as IL-2, IL-6 and TNF, it has antioxidant effects that protect against ROS and reactive nitrogen species [120]. Zinc also induces the proliferation of cytotoxic T cells [62] and is involved in the production of Th1 cytokines and thus supports the Th1 response [95]. It is essential for the intracellular binding of tyrosine kinase to T cell receptors, which is required for T cell development, differentiation and activation [118] and induces the development of Treg cells and is therefore important for maintaining immune tolerance [120].
Finally, zinc is involved in the production of antibodies [79, 121] and it is important to maintain immune tolerance in recognizing the “self” from “non-self” [64].
Low zinc status impairs many aspects of innate immunity, including phagocytosis, respiratory burst and NK cells activity. Zinc also supports the release of neutrophil extracellular traps, that capture microbes [122].
Zinc malabsorption also displays severe immune impairments and increased susceptibility to bacterial, viral and fungal infections. It has widely been suggested that increasing zinc intakes may be useful against COVID-19 infections, by reducing viral replication and lower respiratory symptoms [123]. Recent systematic reviews report a shorter duration of the common cold in adults with a good level of zinc and a reduced incidence of mortality when it is supplemented to adults with severe pneumonia [124, 125]. Further research will be necessary to support a zinc supplementation in advices. The RDA of zinc, according to the Dietary Recommendation Intake (DRI), is 8–11 mg/day for adults (tolerable upper intake level 40 mg/day), suggesting that a zinc intake of 30–50 mg/day might aid in the RNA viruses control, such as influenza and coronaviruses [98].