Trace Elements Zinc and Selenium: Their Significance in the Conditions of the Covid-19 Pandemic

Within the conditions of the ongoing COVID-19 pandemic, when many questions regarding prevention and treatment strategies remain unsolved and the search for the best antiviral agents is underway, attention should be paid to the role of trace elements zinc and selenium in increasing the body's resistance to viral infections and their direct antiviral activity against SARS-CoV-2. Experimental data show that trace elements zinc and selenium not only actthrough regulating the immune response at all levels of humoral and cellular immunity, but also can play a significant role in adjuvant therapy for viral diseases. This is especially relevant in the case of COVID-19. Studies of the direct antiviral effect of these micro-elements testify to its 3 main ways to SARS-Cov-2: I - counteraction to virus replication and its transcription through: (i) their covalent binding to the SH-group of the cysteine of the main protease M(Pro) of the virus;(ii) inhibition of its RNA polymerase activity by zinc;II - preventing the penetration of the virus into cells due to blocking SH-groups of protein disulfide isomerase (RDI) of the protein of its spikes (peplomers);III - decreasing the adsorption capacity of the virus due to the blocking of the electrostatic interaction of SARS-CoV-2 peplomers and angiotensin-converting enzyme (ACE-2) in ultra-low, uncharacteristic oxidation states (Zn+1and Se-2). The intensity of the antiviral action of these trace elements may depend on their chemical form. It was found that zinc citrate (a five-membered complex of zinc with citric acid) and monoselenium citric acid obtained with the help of nanotechnology have a greater intensity of action and higher chemical purity. Taking into account the immunostimulating and direct antiviral effect of zinc and selenium, their use in the form of pharmaceuticals and dietary supplements should be considered as adjunctive therapy for SARS-CoV-2 in patients, or as a preventive strategy for uninfected people from risk groups during the spread of COVID-19.Copyright © Publisher PH <<Akademperiodyka>> of the NAS of Ukraine, 2023.

A Review: Zinc as an Antivirus Alternative Treatment for Herpes Simplex Virus Infection

This study aimed to review zinc's effectiveness as an antivirus in treating herpes simplex virus infection. The authors use international journals published from 2000-2022, and use search engines such as Google Scholar, PubMed, and Science Direct with the keywords "zinc and herpes simplex virus". The herpes simplex virus that often causes symptoms in humans are HSV type 1 and type 2. The lesions appear as vesicles which then rupture into ulcers. Zinc is one of the most abundant nutrients or metals in the human body besides iron. Studies about the effects of zinc on HSV have shown that it has the function of inhibiting the viral life cycle. HSV attaches to the host cells to replicate and synthesize new viral proteins. Zinc can inhibit this process by depositing on the surface of the virion and inactivating the enzymatic function which is required for the attachment to the host cell, disrupting the surface glycoprotein of the viral membrane so it could not adhere and carry out the next life cycle, it can also inhibit the function of DNA polymerase that works for viral replication in the host cell. This article showed that zinc has effectiveness as an antivirus against the herpes simplex virus, therefore, patients infected with HSV can be treated with zinc as an alternative to an antivirus drug.Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd.

Zinc and its impact on human health in conditions of covid-19 pandemic: What's new?.

The article is devoted to the role of the micronutrient zinc in maintaining health as well as in the formation of diseases. The data on the effect of zinc on the immune system, its participation in metabolic processes are presented, its anti-inflammatory effects and the effect on anti-infectious protection are highlighted. The reasons for the development of zinc-deficiency states, their clinical manifestations, as well as recommendations for correction are considered. On the base of modern research, the authors present the advantages of using zinc in SARS, including the prospects for its use in case of COVID-19.Copyright © 2021, Professionalnye Izdaniya. All rights reserved.

Zinc and its impact on human health in conditions of covid-19 pandemic: What's new?.

The article is devoted to the role of the micronutrient zinc in maintaining health as well as in the formation of diseases. The data on the effect of zinc on the immune system, its participation in metabolic processes are presented, its anti-inflammatory effects and the effect on anti-infectious protection are highlighted. The reasons for the development of zinc-deficiency states, their clinical manifestations, as well as recommendations for correction are considered. On the base of modern research, the authors present the advantages of using zinc in SARS, including the prospects for its use in case of COVID-19.Copyright © 2021, Professionalnye Izdaniya. All rights reserved.

Bioavailability of iron and its potential to improve the immune system and ward off COVID-19: a review

Iron is a mineral that plays an important role, especially to prevent anaemia through the production of red blood cells. Iron also plays a role in physiological processes, such as the activation of enzymes and hormones, as well as increasing the immune system in warding off various viral infections. Therefore, iron bioavailability needs to be considered to take the greatest benefit of iron. This review discussed the factors that can affect the bioavailability of iron, various technologies to increase the bioavailability, and its potential in enhancing the immune system. Iron bioavailability can be increased by fortification, fermentation, the addition of vitamin C, and iron encapsulation. Under conditions of adequate iron intake, iron plays an important role in enhancing the immune system through controlling lymphocytes and T cell proliferation. However, excess iron consumption can be at risk of weakening the host's immune response to viruses. Therefore, the appropriate level of iron intake must be maintained accurately to be used optimally and has the potential to ward off viral infections, including the Sars-CoV-2 virus as the cause of COVID-19.Copyright © 2023, Rynnye Lyan Resources. All rights reserved.

Relationship Between Anosmia, Interleukin-6, and Disease Course of SARS COVID-19 Infection

Background: Olfactory dysfunction became increasingly popular as an early symptom of COVID-19 infection, associated with a positive outcome and milder course of the disease. Initial studies suggest that interleukin-6 directly damages the olfactory bulb, thus playing an important role in the mechanism of anosmia. Higher plasma levels of interleukin-6, on the other hand, are related to the severe course of the disease after COVID-19 infection. Methods: The present study explores the predictive power and the relationship between anosmia and plasma levels of interleukin-6 in 122 patients who were hospitalized with COVID-19 in the period March to November 2021 in the Hospital Base for Active Treatment of Military Medical Academy, Varna, Bulgaria. Results: The positive correlation between plasma levels of interleukin-6 and disease severity was confirmed. Also, we observed a significant decrease in interleukin-6 plasma levels during the course of the disease in patients with a favorable outcome. There was no statistically significant difference between plasma levels of interleukin-6 in recovered patients with and without anosmia. We also reported a high percentage of hospitalized and deceased patients with anosmia. Conclusions: In patients with moderate-to-severe SARS CoV-2 infection, anosmia has not been proven to be a prognostic sign for a positive outcome of the disease. However, our data show that plasma levels of interleukin-6 have good predictive power for the course and outcome of the infection. We found a positive correlation between interleukin-6 and the severity of the disease. Favorable outcome was most often preceded by a rapid drop in interleukin-6 levels.

Zinc and COVID-19: Immunity, Susceptibility, Severity and Intervention.

During the coronavirus disease 2019 (COVID-19) pandemic and continuing emergence of viral mutants, there has been a lack of effective treatment methods. Zinc maintains immune function, with direct and indirect antiviral activities. Zinc nutritional status is a critical factor in antiviral immune responses. Importantly, COVID-19 and zinc deficiency overlap in high-risk population. Hence, the potential effect of zinc as a preventive and adjunct therapy for COVID-19 is intriguing. Here, this review summarizes the immune and antiviral function of zinc, the relationship between zinc levels, susceptibility, and severity of COVID-19, and the effect of zinc supplementation on COVID-19. Existing studies have confirmed that zinc deficiency was associated with COVID-19 susceptibility and severity. Zinc supplementation plays a potentially protective role in enhancing immunity, decreasing susceptibility, shortening illness duration, and reducing the severity of COVID-19. We recommend that zinc levels should be monitored, particularly in COVID-19 patients, and zinc as a preventive and adjunct therapy for COVID-19 should be considered for groups at risk of zinc deficiency to reduce susceptibility and disease severity.

SCARED INTO SCURVY: NUTRITIONAL DEFICIENCIES DUE TO FEAR OF COVID-19

CASE: A 26-year-old male presented to the hospital with 2 weeks of difficulty ambulating, bilateral lower extremity rash, and diffuse myalgia with arthralgia. Symptoms began suddenly with lower extremity pain and difficulty getting up from his chair. He denied sensory changes, and pain was most prominent at the hips and knees. He also noticed a new rash on his thighs and mild bleeding from his gums. All other review of systems were negative. He denied family history of autoimmune disease and was without any personal chronic medical conditions. He was the primary caretaker of his grandmother and had stayed isolated at home throughout the COVID-19 pandemic. Vital signs were normal, and physical exam revealed 3/5 right hip flexion, 4/5 left hip flexion, and 4/5 right knee flexion and extension. Inspection of his rash demonstrated follicular hyperkeratosis, perifollicular erythema, and corkscrew hairs. Initial lab work revealed anemia, hypothyroidism, hypotonic hyponatremia, hypocalcemia, an elevated CK, ESR, and CRP. Extensive infectious and autoimmune workup was unrevealing. Further interview revealed that his diet consisted of soy milk, potato chips, crackers, peanut butter, and water in the preceding 6 months. This was intentionally done to reduce exposure to SARS- CoV-2. Further evaluation revealed Vitamin C, Vitamin D, Zinc, and Iron deficiencies. His presenting symptoms and rash were ultimately attributed to hypothyroid myopathy and Scurvy. Following thyroid replacement therapy, dietary education, and nutritional supplementation, he experienced improvement in his symptoms and rash. IMPACT/DISCUSSION: It has become evident that the COVID-19 pandemic has had significant psychosocial impact on the public, with substantial portions of our population experiencing increased fear and anxiety. Interestingly, a longitudinal study by Pan et al. found that Dutch patients without prior mental health disorders, such as our patient, had a more significant increase in depression, anxiety, and worry during the pandemic. To add to this, a study by Izzo et al. found that a substantial part of their study population had turned to unhealthy nutritional behaviors during the pandemic. Furthermore, Nguyen et al. demonstrated that increased health literacy was protective against the negative psychological impacts of the COVID-19 pandemic. Our case presents an outcome of merging pandemic fears with poor health literacy. It also highlights the critical role of the clinician as historian. Conceptualizing the patient's clinical presentation with their daily life ultimately led to appropriate diagnostic workup and treatment. CONCLUSION: As the COVID-19 pandemic continues, its broader and less apparent effects will continue to be seen. Clinicians must remain vigilant in assessing the changes in their patients' daily lives with open and invested communication. Early identification of potentially harmful changes and improved health education could prevent potential complications.

MEASUREMENT OF VITAMIN D3 AND ZINC LEVELS IN COVID-19 PATIENTS WITH WIDESPREAD HAIR LOSS IN BAGHDAD CITY

Zinc has an important role during infection with the Covid-19 virus, as it regulates the work of the immune system. Zinc deficiency leads to hair loss and graying and affects the functioning of the thyroid hormone. Between 15% and 30% of Covid-19 patients in the hospital suffer from thyroid dysfunction. However, it appears that most of these changes it is limited and that thyroid function in most patients will return to normal once the infection has cleared. Twenty two males and seventy eight females diagnosed with COVID-19 infection during the period from September 1 to December 12, 2020. All patients were suffering from cough, fever, hair loss, loss of smell, sweating, loss of appetite and respiratory discomfort. The age of patient was ranged between 15 to 70 years. 2019-nCoV IgG/IgM COMBO test card was used to diagnose SARS-COV-2 infection. Serum zinc concentration;serum Ferritin levels;TSH;T4 and serum Vitamin D3 were estimated in all patients. The highest rate of infection with the COVID-19 was in females, with a rate of 28.20% within the age group 30-39 years, as well as in males, and a percentage of 36.36% within the same age group. 86 (86%), 74 (74%), 68 (68%) and 18 (18%) patients from a deficiency in TSH, ferritin, Vitamin D3 and zinc levels, respectively. The age group 30-39 years of patients suffered from low levels of zinc, as it was 11 (61.1%), followed by the age group 40-49 years, with a rate of 4 (22.2%). The levels of TSH, ferritin and Vitamin D3 in the age group 30-39 years were 30 (34.8%), 21 (14.28%) and 25 (33.78%), respectively. While the T3 and T4 rates for all patients and for all age groups were within normal levels. In conclusion, COVID-19 patients suffered from zinc deficiency and thyroid dysfunction with significant hair loss in almost all age groups and both sexes.

ZINC DEFICIENCY IS INDEPENDENTLY ASSOCIATED with INCREASED COVID-19 DISEASE SEVERITY

Background: COVID-19 has the most impact on people with comorbidities likely due to a higher inflammatory state. Zinc (Zn) is known for its substantial involvement in immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels' clinical significance at COVID diagnosis is not yet established. We investigated the effects of Zn deficiency and inflammation on COVID-19 outcomes. Methods: Plasma Zn levels were collected from patients during the acute phase of a confirmed COVID-19 diagnosis. Data was dichotomized into Zn deficient (Zn<75 μ g/dL) and Zn sufficient (Zn ≥75 μ g/dL). Soluble tumor necrosis factor alpha receptor II (sTNF-RII) and intestinal fatty-acid binding protein (I-FABP) were also measured. COVID-19 outcomes were classified according to the WHO clinical progression scale (0-10), then stratified into 3 groups [grp 1= (WHO score 0-4) asymptomatic or mild disease;moderate grp 2= (WHO 5-6), and severe grp 3= (7-10)]. Hazard ratios (AHRs) and 95% Confidence Intervals (CIs) were computed using cumulative logit regression and adjusted for demographics, BMI, comorbidities, inflammation markers, and laboratory data. Results: We included 149 patients with a confirmed COVID-19 diagnosis. The median age (interquartile range [IQR]) was 53 years (38.0, 63.0);42% of the patients were female, 52% non-white, and 86% had at least one comorbidity. Overall, 50% of patients were in grp 1= asymptomatic or mild, whereas 8.5% had the worse outcome (grp 3). More than half of the participants (54%) had sufficient zinc levels. There was not enough evidence to suggest any differences regarding age, gender, body mass index (BMI), hemoglobin, white blood cells, transaminases enzymes, I-FABP, and sTNF-RII between the Zn-sufficient and deficient arms (p>0.05). However, 21% of the Zn sufficient arm were non-White compared to 31% in the deficient arm (p= 0.0004). Patients with zinc deficiency had a median BMI of 31.96 kg/m2 (IQR: 26.69, 36.44) and a median sTNF-RII of 3027.00 (IQR: 2446.00, 4468.00). In adjusted models, as zinc levels decreased, the risk of severe COVID-19 outcomes increased [AHR: 0.24 (95% CI: 0.06, 0.93)]. As sTNF-RII increases, but not I-FABP, the risk of severe COVID-19 outcomes rises two-fold [AHR: 2.17 (95% CI: 1.10, 4.31)]. Conclusion: Zinc deficiency and higher levels of sTNF-RII during acute COVID-19 presentation are independently associated with worse outcomes, suggesting a potential relationship between these 2 variables in COVID-19 progression.

Zinc deficiency: Which matrix should we use?

BACKGROUND AND AIM: Zinc is a multifunctional trace element. Due to its positive effects on the immune system, the use of zinc supplements has become widespread during the COVID 19 pandemic Both zinc deficiency and excess intake can lead to significant health problems. In this study;we aimed to compare serum and intra-erythrocyte zinc levels to determine most appropriate matrice in requirement and follow-up of zinc replacement. METHODS: Simultaneously measured serum and intra-erythrocyte zinc levels obtained from 285 patients admitted to our laborotory between 2000-2021 were scanned retrospectively. Atomic absorption spectroscopy method had been used for measurements. Quantitative results of the two different matrices were analyzed by simple linear regression analysis. The agreement between the classifications obtained according to the reference interval was evaluated with kappa statistics. RESULTS: A very weak agreement was observed between intra-erythrocyte and serum zinc measurements according to classification agreement (Kappa statistic=0.000;p=0.994). 149 (59.6%) of 250 results in serum were normal, whereas low in intra-erythrocytes. 6 of results were low in intra-erythrocytes, whereas were high in serum and 2 of results were high in intra-erythrocytes whereas were low in serum samples. The relationship between the measurements of the two matrices was not significant in the linear regression analysis (B=0.011;r=0.106;p=0.073). CONCLUSIONS: These findings indicate that serum measurement may be insufficient to detect zinc deficiency. In the light of these findings, it was decided to study both matrices together in terms of functional target and to follow the clinical correlation in the follow-up of zinc replacement therapy in our laboratory.

Gustatory and Saliva Secretory Dysfunctions in COVID-19 Patients with Zinc Deficiency.

Given the ever-progressing studies on coronavirus disease 2019 (COVID-19), it is critical to update our knowledge about COVID-19 symptomatology and pathophysiology. In the present narrative review, oral symptoms were overviewed using the latest data and their pathogenesis was hypothetically speculated. PubMed, LitCovid, ProQuest, and Google Scholar were searched for relevant studies from 1 April 2021 with a cutoff date of 31 January 2022. The literature search indicated that gustatory dysfunction and saliva secretory dysfunction are prevalent in COVID-19 patients and both dysfunctions persist after recovery from the disease, suggesting the pathogenic mechanism common to these cooccurring symptoms. COVID-19 patients are characterized by hypozincemia, in which zinc is possibly redistributed from blood to the liver at the expense of zinc in other tissues. If COVID-19 induces intracellular zinc deficiency, the activity of zinc-metalloenzyme carbonic anhydrase localized in taste buds and salivary glands may be influenced to adversely affect gustatory and saliva secretory functions. Zinc-binding metallothioneins and zinc transporters, which cooperatively control cellular zinc homeostasis, are expressed in oral tissues participating in taste and saliva secretion. Their expression dysregulation associated with COVID-19-induced zinc deficiency may have some effect on oral functions. Zinc supplementation is expected to improve oral symptoms in COVID-19 patients.

Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections – a living rapid review and meta-analysis

Introduction: This living rapid review aims to systematically update evidence from randomised controlled trials (RCTs) on the efficacy and safety of any zinc formulation or dose compared to any control, for preventing or treating SARS-CoV-2 and other acute viral respiratory tract infections (RTIs) in adults. Methods: Protocol registration was 27-April-2020 (PROSPERO: CRD42020182044). Eight databases (one Chinese), four clinical trial registries (one Chinese) and two pre-print servers were then searched with no language or date restrictions. Post-protocol/pre-data extraction, the inclusion criteria was restricted to adults. Meta-analysis used weighted, random-effects models. Cochrane RoB 2.0 tool and GRADE were used to appraise evidence certainty. Searches for COVID-19 evidence are updated 6-monthly. Results: As of Oct-2020, 1,907 articles and protocols were screened, and 28 RCTs involving 5,403 participants (none with SARS-CoV-2 infections) were included. Compared to placebo, oral or intranasal zinc prevented 5 RTIs/100 person-months (95%CI: 1-9, NTT=20) in adults without zinc deficiency (moderate-certainty), but not pre/post exposure prevention following human rhinovirus inoculation (RR 0.96, 95%CI: 0.77-1.21, moderate-certainty). There was low-certainty evidence of clinically important RTI treatment outcomes. Compared to placebo, sublingual or intranasal zinc improved day-3 symptom severity (MD 1.2 points lower, 95%CI: 0.7-1.7) and reduced symptom duration (MD 2 days shorter, 95%CI: 0.2-3.5;HR 0.55 over 7-days, 95% CI: 0.32-0.91, NNT=5). There was an increased risk of non-serious adverse events (e.g. nausea, or mouth or nasal irritation) (ARR 14/100 adults, 95%CI: 4-16, NNH=7). In the 25 RCTs that reported adverse events, none were serious, including copper deficiency or anosmia. The April-2021 update search identified, four COVID-19 RCTs with 572 participants and 7 registered RCTs. These results will be included in the next update. Conclusion: Preliminary evidence suggests there may be a role for zinc in the COVID-19 pandemic. Further research and regular updating of the evidence is warranted. Keywords: Zinc, Complementary medicine, Common cold, Respiratory infections, Viral infections, COVID-19

The Role of Micronutrients and Toxic Metals in the Management of Epidemics in Cambodia.

The illegal trade of wildlife in SE Asia has been identified as the likely cause of the COVID-19 pandemic. We reviewed 198 papers on the current COVID pandemic in Cambodia, diseases such as avian influenza and Nipah virus, most likely to develop into a new pandemic in Cambodia, and common features of disease that require mitigation. Artisanal goldmining uses pure mercury in the areas where wildlife is smuggled to China. Moreover, 30-40% of Cambodians are zinc deficient. High levels of arsenic in irrigation water (>1000 µg/L) are associated with very low levels of zinc in rice (5 µg/g) and rice is the primary staple food for the region. Brown rice from nine of 15 paddy fields in the arsenic zone of Cambodia had double the new guidelines of 100 µg/kg inorganic arsenic for children's food in the EU and USA. The combination of deficiencies of essential micronutrients like zinc and pervasive presence of arsenic and mercury has the potential to compromise the immunity of many Cambodians. Innovative solutions are suggested to improve micronutrient nutrition. Toxins that suppress the immune system must be better managed to reduce the virulence of pathogens. Cambodia was not likely the source of the COVID-19 but does have problems that could result in a new pandemic.

COVID-19: Zinc and Angiotensin-Converting Enzyme 2 (ACE2) Deficiencies as Determinants of Risk and Severity of Disease: A Narrative Review.

A growing body of evidence supports the premise that deficiencies of zinc and angiotensin-converting enzyme 2 (ACE2, a zinc enzyme) determine severity of coronavirus disease 2019 (COVID-19). ACE2 is part of the renin-angiotensin system (RAS) and acts as a feedback control system moderating blood pressure, keeping blood pressure within normal limits. For a virus to infect a person, the virus has to get inside the person's cells. The virus that causes COVID-19 uses ACE2 to get into the cell. Think of this like an invader from outer space attacking your car by getting in through your cruise control; the RAS is like the cruise control of your car. What happens next depends on how robust your cruise control is. If your cruise control is young and healthy perhaps very little happens; your car may slow down or speed up a bit. But if your cruise control is in poor condition the attack might disrupt the entire speed control system; your car may brake suddenly or speed out of control and crash. Feedback control systems (natural or man-made) are designed to keep dynamic systems in control, but under certain situations can drive the system completely out of control. The RAS is composed of two feedback loops: the ACE loop provides amplification, increasing pro-inflammatory cytokines and blood pressure; the ACE2 loop provides fine control and mitigates the vasoconstrictive, pro-inflammatory, and thrombotic actions of the ACE loop. Usually, there is balance, but in the setting of COVID-19, underlying deficiencies of zinc and ACE2 can lead to an imbalance. Exacerbated by the severe downregulation of ACE2 seen with viral entry, a "tipping point" is reached with loss of control of the RAS system resulting in increased angiotensin II (Ang II) causing downstream vasoconstriction, inflammation, and thromboses. These, in turn, lead to complications often seen in "severe COVID-19" such as acute respiratory distress syndrome (ARDS) or cytokine storm, often seen in high-risk patients in the second week of illness. This model suggests that supplemental zinc could replenish zinc in ACE2, stabilize the ACE2 axis, and prevent disruption of the RAS. This would prevent the vasoconstrictive, inflammatory, and thrombotic actions of Ang II, thus preventing the severe COVID-19 complications which cause the high morbidity and mortality seen in high-risk patients with underlying zinc deficiency. Zinc supplements are available, easy to use, and relatively safe. Randomized clinical trials are needed to confirm safety and efficacy of zinc supplementation to decrease severity of and morality from COVID-19 in high-risk patients. Since replenishment of zinc and active ACE2 in patients in whom these are deficient may take weeks, supplementation in high-risk populations prior to COVID infection may be required. Such supplementation should not replace vaccination but may be useful in populations for whom vaccination is not available or for populations exposed to viral variants to which available vaccines have insufficient coverage.

[Zinc status improving as a pathogenetically grounded platform for maintaining immunity during SARS-CoV-2 pandemic].

The problem of increasing immunity has become especially relevant in the conditions of the rapid spread of the new coronavirus infection SARS-CoV-2. Nowadays it has been proven that a deficiency of certain micronutrients in the diet can disrupt chemical, structural and regulatory processes in the organism, which negatively affects, first of all, the state of immune system. Zinc is one of the most significant essential trace elements affecting immunological resistance. The aim of the study was to substantiate the need of including zinc-containing products and diet supplements in the diet of the population during the SARS-CoV-2 pandemic on the basis of the study of pathogenetic mechanisms of various disorders of the immunological status under zinc deficit. Material and methods. This review analyzes the data from scientific electronic libraries CyberLeninka, eLIBRARY.RU, the Google Scholar databases and bibliographic medical databases MEDLINE and PubMed-NCBI. Results and discussion. During the SARS-CoV-2 pandemic, adequate zinc supply is especially important, due to its antiviral, immunomodulatory and antiapoptotic effects. This element also regulates the severity of the cytokine response, exhibits antibacterial properties and helps to compensate for chronic comorbid diseases, which plays a particularly significant role in preventing severe SARS-CoV-2 and recurrent respiratory diseases. Prevention and correction of zinc deficiency is considered as one of the important measures during the SARS-CoV-2 pandemic, aimed at increasing antiviral and general immunity, reducing the systemic inflammatory response and correcting hormonal and metabolic status. Conclusion. The pathogenetically substantiated inclusion of zinc-containing foods and supplements in the diet will enhance the immunity of the population during the SARSCoV- 2 pandemic.

Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19.

The importance of Zn for human health becomes obvious during Zn deficiency. Even mild insufficiencies of Zn cause alterations in haematopoiesis and immune functions, resulting in a proinflammatory phenotype and a disturbed redox metabolism. Although immune system malfunction has the most obvious effect, the functions of several tissue cell types are disturbed if Zn supply is limiting. Adhesion molecules and tight junction proteins decrease, while cell death increases, generating barrier dysfunction and possibly organ failure. Taken together, Zn deficiency both weakens the resistance of the human body towards pathogens and at the same time increases the danger of an overactive immune response that may cause tissue damage. The case numbers of Corona Virus Disease 19 (COVID-19) are still increasing, which is causing enormous problems for health systems and economies. There is an urgent need to reduce both the number of severe cases and the resulting deaths. While therapeutic options are still under investigation, and first vaccines have been approved, cost-effective ways to reduce the likelihood of or even prevent infection, and the transition from mild symptoms to more serious detrimental disease, are highly desirable. Nutritional supplementation might be an effective option to achieve these aims. In this review, we discuss known Zn deficiency effects in the context of an infection with Severe Acute Respiratory Syndrome-Coronavirus-2 and its currently known pathogenic mechanisms and elaborate on how severe pre-existing Zn deficiency may pre-dispose patients to a severe progression of COVID-19. First published clinical data on the association of Zn homoeostasis with COVID-19 and registered studies in progress are listed.

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis.

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.