During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.
Risk Groups and Symptoms of COVID-19 and Zinc Deficiency Reveal a Large Overlap
The intersection between risk groups of COVID-19 and zinc deficiency is impressive. In patients with chronic obstructive pulmonary disease (COPD), bronchial asthma, cardiovascular diseases, autoimmune diseases, kidney diseases, dialysis, obesity, diabetes, cancer, atherosclerosis, liver cirrhosis, immunosuppression, and known liver damage low serum zinc levels are regularly observed . At the same time, these groups are particular at risk for COVID-19 For example 57.5% elderly and nursing home residents in the U.S., for which high incidence of respiratory tract infections is described, showed significantly decreased zinc intake levels and are considered subjects with high risk regarding COVID-19 . Moreover, other studies showed that serum zinc levels were inversely correlated with pneumonia and cystic fibrosis . On the other hand, zinc supplementation was able to reconstitute immune function in elderly and zinc deficient individuals , which remains to be addressed for SARS-CoV2 infections. In this regard, the low response of older patients with low serum zinc to a 23-valent pneumococcal polysaccharide vaccination compared to those with higher zinc level, should be mentioned. However, zinc's role in the response to vaccination is generally discussed controversially and no data are available for vaccination against any corona virus.
Several studies indicate that there is an association between chemosensory dysfunctions and COVID-19. Smell or taste is largely decreased, which might be a good disease biomarker. It was suggested that this might either be due to direct destruction of sensory cells by the virus, as ACE-2 is highly expressed by the oral mucosa, or by viral entry into the brain and neuronal pathologies as was described for other SARS-CoV. Zinc deficiency was related to significantly reduced taste sensitivity and impaired saliva secretion in humans and animals, which might involve zinc's importance for the action of carbonic anhydrase. Results from supplementation studies largely describe improvements in chemosensory functions, but some studies did not find any effects or even more severe disturbances when very high zinc concentrations were used. This is possibly due to investigating olfactory diseases of various origins, the lack of controlled trials and inclusion of observable studies. Thus, the benefits of zinc supplementation alone or in combination with common medical strategies should be tested for taste and smell diseases according to the available guidelines.
About 50% of patients that died of COVID-19 had bacterial or fungal co-infections, underlining the importance of sustaining the immune function by a sufficient zinc supply. In animal experiments it was shown that zinc restriction made mice highly susceptible to bacterial infection with streptococcus pneumoniae . As mentioned earlier, marginal zinc deficiency affects one third of the worldwide population and most subjects with COVID-19 are at risk of zinc deficiency. During physiological inflammatory responses, zinc is additionally redistributed to the tissues, resulting in serum hypozincemia. In combination with the pre-existing suboptimal zinc supply, this will decrease serum zinc levels to critically low values and thereby significantly increase the susceptibility for co-infections with detrimental progression. In critically ill patients persistent low serum zinc was associated with recurrent sepsis and serum zinc levels were inversely correlated with mortality from sepsis, underlining the potential benefits of monitoring the zinc status of the patients and implementing zinc supplementation into therapy of COVID-19.
Vascular complications resulting from atherosclerosis development, microangiopathic organ failure, and venous thromboembolism were found as a major cause of death in COVID-19 patients, suggesting an important role of disease-induced coagulopathy, which, however, needs further investigation. Zinc influences thrombocyte aggregation and coagulation. Recently, a functional association between zinc and ROS production in platelets was described, indicating that zinc could decrease thrombus formation in a clinical context. Complications of SARS-CoV2 infections also include tissue damage affecting the gastrointestinal system, the liver, heart, nervous system, kidneys, blood vessels, and the skin. In this regard it should be mentioned that a balanced zinc homeostasis is essential for wound healing and tissue recovery after mechanical and inflammation-mediated damage, adding more potential benefits of zinc supplementation of COVID-19 patients.
In this perspective, we reviewed the most important literature on the role of zinc homeostasis during viral infections, focusing on the potential benefits of zinc supplementation to prevent and treat SARS-CoV2 infections. Although data specifically on SARS-CoV2 are unfortunately still pending and randomized controlled studies have not been conducted, the enumerated evidence from the literature strongly suggests great benefits of zinc supplementation. Zinc supplementation improves the mucociliary clearance, strengthens the integrity of the epithelium, decreases viral replication, preserves antiviral immunity, attenuates the risk of hyper-inflammation, supports anti-oxidative effects and thus reduces lung damage and minimized secondary infections. Especially older subjects, patients with chronic diseases and most of the remaining COVID-19 risk groups would most likely benefit. Although studies are needed testing the effect of zinc as therapeutic option for established disease, preventive supplementation of subjects from risk groups should begin now, as zinc is a cost-efficient, globally available and simple to use option with little to no side effects. The first clinical trials on zinc supplementation alone and in combination with other drugs such as chloroquine have been registered. Thus, first results and treatment regimens regarding zinc supplementation for COVID-19 risk groups and patients can be anticipated soon
Reference & source information: https://www.frontiersin.org/
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