Several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating COVID-19. Because of their potential to influence immune response, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19.
The authors outline the biologic plausibility, applicable clinical data, and potential role of each of these agents.
As of yet, there is no high-quality evidence to support medication therapy for the prevention or treatment of patients with coronavirus disease 2019 (COVID-19). However, several agents intended to supplement dietary intake or endogenous molecules may have a theoretical role in preventing or treating the disease.
COVID-19 infection leads to upregulation of systemic inflammation as evidenced by elevated concentrations of pro-inflammatory cytokines interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF) alpha, as well as higher concentrations of the anti-inflammatory cytokine IL-10.
Additionally, patients with COVID-19 likely have evidence of oxidative stress, which is characterized by production of reactive oxygen species and reactive nitrogen species, and a concomitant deficiency of antioxidants. Reactive oxygen species and reactive nitrogen species are known to damage cellular biochemical pathways by causing DNA strand breaks, lipid peroxidation, and antioxidant and antiprotease degradation.
There are multiple defense mechanisms against reactive oxygen species and nitrogen species, including enzymatic scavengers (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic molecules (glutathione and vitamins A, C, and E).
It is the imbalance between production of reactive oxygen and nitrogen species and the antioxidant pool in the body that perpetuates further damage and, with a hyperinflammatory response, may contribute to severe manifestations of COVID-19.
Because of their potential to influence immune response and reactive oxygen and nitrogen species, and because of their availability as over-the-counter medications, ascorbic acid (vitamin C), zinc, vitamin D, and N-acetylcysteine have been hypothesized to be useful for prevention or treatment of COVID-19. The biologic plausibility, applicable clinical data, and potential role of each of these agents are outlined below.
Ascorbic acid is known to function as an antioxidant by savaging ROS, and a number of studies have suggested that vitamin C supplementation can impact the immune system.
Moreover, in vitro and in vivo studies in avians have shown that vitamin C could be protective against avian coronavirus infection, and human trials have found that vitamin C may decrease susceptibility to viral respiratory infections and pneumonia. High doses of ascorbic acid reduce the severity and duration of symptoms from the common cold, which is caused by rhinovirus.
Studies of vitamin C for the treatment of hospitalized and critically ill patients have shown mixed results on mortality, length of stay in the intensive care unit, and duration of mechanical ventilation. However, high doses of intravenous vitamin C were generally safe. The impact of vitamin C for the treatment of patients with COVID-19 is unclear, and new clinical trials are under way in China and the United States.
Zinc is known to be important for immune function and has a role in antibody and white blood cell production. Deficiency of zinc increases pro-inflammatory cytokine (IL-1, IL-6, and TNF alpha) concentrations and decreases the production of antibodies, while zinc supplementation has been shown to increase the ability of polymorphonuclear cells to fight infection.
Zinc has also been implicated in coronavirus biology, with increasing intracellular concentrations of zinc demonstrated to inhibit virus RNA polymerase activity and viral replication in an in vitro and cell culture model of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1). In a meta-analysis evaluating studies comparing zinc supplementation and placebo, high-dose zinc reduced the duration but not the severity of symptoms of the common cold.
Overall adverse effects and specifically nausea were significantly more frequent with zinc (which may have been dose-dependent), and the effect of prophylactic zinc supplementation was inconclusive.
Whether zinc supplementation can benefit patients with lower respiratory tract infections such as COVID-19 is unclear. Because of its role in immune function and potential to decrease coronavirus replication, zinc is currently being investigated for prophylaxis and treatment of patients with COVID-19.