As global life expectancy increases, research reveals a critical challenge in aging: the progressive deterioration of immune function, termed immunosenescence. This age-related immune decline is characterized by a complex dysregulation of immune responses, which leaves older adults increasingly vulnerable to infections, chronic inflammatory states, and various degenerative diseases. Without intervention, immunosenescence significantly contributes to morbidity and mortality among the elderly, intensifying healthcare burdens and diminishing quality of life on both individual and societal levels. This review explores the essential role of zinc, a trace element critical for immune health, in mitigating the impact of immunosenescence and slowing the cascade of immunological dysfunctions associated with aging. By modulating the activity of key immune cells and pathways, zinc supplementation emerges as a promising approach to strengthen immunity, reduce oxidative stress, and counteract "inflammaging," a state of chronic, low-grade inflammation that accelerates tissue damage and drives disease progression. Zinc's involvement in cellular defense and repair mechanisms across the immune system highlights its ability to enhance immune cell functionality, resilience, and adaptability, strengthening the body's resistance to infection and its ability to manage stressors that contribute to diseases of aging. Indeed, zinc has demonstrated potential to improve immune responses, decrease inflammation, and mitigate the risk of age-related conditions including diabetes, depression, cardiovascular disease, and vision loss. Given the prevalent barriers to adequate zinc intake among older adults, including dietary limitations, decreased absorption, and interactions with medications, this review underscores the urgent need to address zinc deficiency in aging populations. Recent findings on zinc's cellular and molecular effects on immune health present zinc supplementation as a practical, accessible intervention for supporting healthier aging and improving quality of life. By integrating zinc into targeted strategies, public health efforts may not only sustain immunity in the elderly but also extend healthy longevity, reduce healthcare costs, and potentially mitigate the incidence and impact of chronic diseases that strain healthcare systems worldwide.

In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a 'bacteriophage-like' behaviour of SARS-CoV-2.

We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2.

Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures.

Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.

Zinc plays an important role in the functioning of the immune system. Zinc deficiency leads to increased susceptibility to inflammatory and infectious diseases. There are few studies investigating the role of zinc in the development and progression of COVID-19 in children, and their findings remain inconsistent. This study aimed to determine the zinc levels in children with COVID-19 and assess their association with symptoms, inflammation markers, and disease progression.

A prospective cohort study included hospitalized patients under 18 years who had a confirmed diagnosis of SARS-CoV-2 infection. Serum zinc concentrations were measured using a colorimetric method. Based on zinc levels, the children were divided into two groups: the first group had concentrations below 10.7 μmol/L, indicating zinc deficiency, while the second group had levels above 10.7 μmol/L, which was considered within the optimal range.

In total, 140 hospitalized patients with COVID-19 were examined. Zinc deficiency was identified in 40 children (28.6%), while optimal levels were found in 100 children (71.4%). Zinc status did not depend on the age of the children. Among the symptoms of acute SARS-CoV-2 infection, children with zinc deficiency showed a trend toward more frequent fever occurrences (p = 0.0654). No significant impact of zinc status was observed on the severity of COVID-19 or the duration of hospitalization. Children with zinc deficiency had higher median values of the neutrophil-to-lymphocyte ratio (NLR) (1.84 vs. 1.09, p = 0.0010), C-reactive protein (CRP) levels (9.65 vs. 3.96 mg/L, p = 0.0053), and fibrinogen levels (2.88 vs. 2.07 g/L, p = 0.0057) compared to those with adequate zinc levels. Additionally, the percentage of patients with a NLR greater than 4, elevated CRP, and fibrinogen levels was higher in the zinc-deficient group (p = 0.0017, p = 0.0107, p = 0.0338, respectively).

Zinc deficiency was observed in 28.6% of children with COVID-19 and was not dependent on age. Children with hypozincemia had higher levels of inflammation markers, including the neutrophil-to-lymphocyte ratio and CRP.

Lassa fever (LF), a viral hemorrhagic disease endemic to West Africa, carries a high mortality. Scanty studies indicate that micronutrients may play a role in immunity to LF. We performed a case-controlled study to evaluate plasma zinc and selenium levels in hospitalized patients with LF.

A cross-sectional controlled study of adults with confirmed LF and healthy controls presenting to the Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Nigeria, was performed between January and April 2023. After informed consent, blood samples were obtained, and LF was confirmed using a real-time polymerase chain reaction assay. Plasma zinc and selenium levels in plasma were measured using the AA500 Atomic Absorption Spectrophotometer. Data analysis was performed using SPSS version 21.0, comparing zinc, selenium, urea, and blood urea nitrogen levels of patients with LF and healthy control patients.

We enrolled 124 patients: 64 patients with LF and 60 healthy controls. There was no difference in mean age (37.6 years vs 35.2 years, P = 0.10) and gender (male 53% vs 56%, P = 0.82). Mean plasma zinc levels were significantly lower in patients with LF (0.97 mg/ml, SD = 0.12) compared with controls (1.85 mg/ml, SD = 0.13; P <0.0001). A consistent depletion of zinc levels was seen across the moderately severe cases (n = 28) and severe cases (36 cases) compared with healthy controls (0.97 ± 0.19 vs 0.96 ± 0.10, P = 0001). Plasma selenium levels were also significantly lower in patients with LF (mean: 76.80 ng/ml, SD: 6.66, % coefficient of variation: 8.67) compared with controls (mean: 93.10 ng/ml, SD: 12.46, % coefficient of variation: 13.38) (P = 0.008). Selenium levels in severe LF cases were 73.47 ± 14.68 and 80.98 ± 18.60 in moderately severe cases (P = 0.26).

Significantly low levels of zinc and selenium were observed in patients with LF compared with healthy controls, suggesting a role in susceptibility and pathogenesis. Given that zinc and selenium are essential trace elements for optimal functioning of the immune system, they may play a role in improving management outcomes.

This review will provide an overview of the immune system and then describe the effects of frailty, obesity, specific micronutrients and the gut microbiota on immunity and susceptibility to infection including data from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic where relevant. A key role for the immune system is providing host defence against pathogens. Impaired immunity predisposes to infections and to more severe infections and weakens the response to vaccination. A range of nutrients, including many micronutrients, play important roles in supporting the immune system to function. The immune system can decline in later life and this is exaggerated by frailty. The immune system is also weakened with obesity, generalised undernutrition and micronutrient deficiencies, which all result in increased susceptibility to infection. Findings obtained during the SARS-CoV-2 pandemic support what was already known about the effects of ageing, frailty and obesity on immunity and susceptibility to infection. Observational studies conducted during the pandemic also support previous findings that multiple micronutrients including vitamins C, D and E, zinc and selenium and long-chain n-3 fatty acids are important for immune health, but whether these nutrients can be used to treat those already with coronavirus disease discovered in 2019 (COVID-19), particularly if already hospitalised, is uncertain from current inconsistent or scant evidence. There is gut dysbiosis in patients with COVID-19 and studies with probiotics report clinical improvements in such patients. There is an inverse association between adherence to a healthy diet and risk of SARS-CoV-2 infection and hospitalisation with COVID-19 which is consistent with the effects of individual nutrients and other dietary components. Addressing frailty, obesity and micronutrient insufficiency will be important to reduce the burden of future pandemics and nutritional considerations need to be a central part of the approach to preventing infections, optimising vaccine responses and promoting recovery from infection.

The contemporary approach to nutrition increasingly considers the role of non-nutritive bioactive compounds in modulating the immune system and maintaining health. This article provides up-to-date insight into the immunomodulatory effects of selected bioactive compounds, including micro- and macronutrients, vitamins, as well as other health-promoting substances, such as omega-3 fatty acids, probiotics, prebiotics, postbiotics (including butyric acid and sodium butyrate), coenzyme Q10, lipoic acid, and plant-derived components such as phenolic acids, flavonoids, coumarins, alkaloids, polyacetylenes, saponins, carotenoids, and terpenoids. Micro- and macronutrients, such as zinc, selenium, magnesium, and iron, play a pivotal role in regulating the immune response and protecting against oxidative stress. Vitamins, especially vitamins C, D, E, and B, are vital for the optimal functioning of the immune system as they facilitate the production of cytokines, the differentiation of immunological cells, and the neutralization of free radicals, among other functions. Omega-3 fatty acids exhibit strong anti-inflammatory effects and enhance immune cell function. Probiotics, prebiotics, and postbiotics modulate the intestinal microbiota, thereby promoting the integrity of the intestinal barrier and communication between the microbiota and the immune system. Coenzyme Q10, renowned for its antioxidant attributes, participates in the protection of cells from oxidative stress and promotes energy processes essential for immune function. Sodium butyrate and lipoic acid exhibit anti-inflammatory effects and facilitate the regeneration of the intestinal epithelium, which is crucial for the maintenance of immune homeostasis. This article emphasizes the necessity of an integrative approach to optimal nutrition that considers not only nutritional but also non-nutritional bioactive compounds to provide adequate support for immune function. Without them, the immune system will never function properly, because it has been adapted to this in the course of evolution. The data presented in this article may serve as a foundation for further research into the potential applications of bioactive components in the prevention and treatment of diseases associated with immune dysfunction.

With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), the main objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection.

Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen.

There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the vallate papillae taste buds (3-35 dpi) and autonomic ganglia (5-35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2-42 dpi).

The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the vallate papillae taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Research proved the beneficial effect of Zinc on human health and Gastrointestinal tract inflammatory diseases. We propose that zinc would be of value in children with Hirschsprung's disease (HD) undergoing elective pull-through surgery. This study was carried out to determine the influence of preoperative zinc intake on postoperative outcomes, especially the hospital length of stay in patients diagnosed with HD as a primary outcome. Other outcomes include identification of the nutritional and inflammatory status including the nutritional and inflammatory markers in children with HD with possible impacts on hospital outcomes.

This is a randomized interventional control study that was applied to 50 children diagnosed with HD who underwent elective pull-through surgery. We randomly allocated 25 diagnosed with HD who underwent elective pull-through surgery. We randomly allocated 25 patients to zinc treatment.

The results demonstrated that the interventional group had a lower incidence of complications (20%) when compared to the control group (64%), with a significant p-value of 0.002. In addition, less incidence of Hirschsprung's associated enterocolitis (HAEC) (12% vs. 40%) and skin excoriation (8% vs. 32%) were documented in the interventional group compared to the controls respectively.

Pre-operative zinc supplementation may have a beneficial impact on HD children undergoing elective pull-through surgery as regards outcomes such as HAEC and skin excoriation.

The exact role of zinc in COVID-19-infected patients is not well understood. We examined the effects and outcomes of zinc deficiency on COVID-19-infected patients. We focused on patient outcomes: severity, symptomatology, and mortality. The meta-analysis was performed to examine whether COVID-19-infected individuals suffered greater symptomology and mortality. Secondary outcomes explored included severity and hospital length of stay. For mortality, we found that COVID-19-infected individuals with zinc deficiency had a greater risk of mortality than individuals without zinc deficiency (risk ratio (RR)=5.77; 95% confidence interval (CI): 3.48, 9.54; p=0.004). For symptomology, we found that COVID-19-infected individuals with zinc deficiency had a greater risk of symptomatology than individuals without a zinc deficiency (RR=1.39; 95% CI: 1.13, 1.70; p=0.020). Zinc-deficient individuals are at a greater risk for mortality and symptomatology. Our findings further reinforce the importance of supplementation as a prophylactic agent against viral infections such as COVID-19.

Barley (Hordeum vulgare) is widely used in the production of beer and distilled beverages, generating a nutrient-rich by-product known as brewer's spent grain (BSG). This study investigates the potential of brewer's spent grain flour (BSGF) as a functional ingredient to enhance the nutritional profile of bakery products, specifically chocolate cakes, while contributing to waste reduction in the food industry. The effects of partially substituting wheat flour with BSGF at 40% and 60% levels were assessed. BSGF was found to be rich in protein (15.5 ± 0.14 g/100 g), zinc (7.92 ± 0.44 mg/100 g), and dietary fiber (52.12 g/100 g). Cakes with 60% BSGF substitution showed increased fiber content (69.8 g/100 g) and zinc content (27.04 g/100 g). Organoleptic evaluation indicated that the tenderness of all three cakes did not show statistical differences. However, among the cakes with BSGF, the 40% substitution level was better accepted by consumers, particularly in terms of flavor. These findings suggest that incorporating BSGF into bakery products can improve nutritional value while offering a sustainable approach to food production by valorizing industry by-products.

The problem of correcting immune system function and compensating for co-morbidities becomes particularly clinically significant in the post-COVID period. There is evidence that certain trace elements in the human body, particularly zinc ions, play a critical role in restoring the function of the immune system and internal organs.

To analyze the mechanisms of zinc action maintaining the body homeostasis in order to justify pathogenetically the inclusion of zinc drugs in the therapy of patients in the post-COVID period.

Data from Elsevier, Global Health, PubMed-NCBI, Embase, MEDLINE, Scopus, Research gate, RSCI Scopus, Cochrane Library, Google Academy, e-LIBRARY.RU and CyberLeninka were used.

This review showed that the importance of zinc in maintaining body homeostasis in the post-COVID period is determined by its multifaceted effect on all parts of the immune system, its anti-inflammatory activity, antimicrobial properties and participation in the restoration of internal organ function. Elimination of zinc deficiency in the post-COVID period is essential to support immunity, compensate for comorbidities and reduce the risk of complications. The impossibility of synthesizing zinc in the body requires its constant intake in sufficient quantities. Zinc levels are significantly reduced after infectious diseases, as this element is specifically distributed to organs and tissues to maintain immunological and metabolic functions. The degree of zinc deficiency is associated with the severity of COVID-19 and the post-COVID period. It is pathogenetically justified to prescribe zinc drugs in the post-COVID period, the choice of which should take into account comorbidities and severity of hypozincemia.

Regularly administered therapy with zinc drugs in the post-COVID period will help correct the population immunity and restore public health.

Research into innovative non-pharmacological therapeutic routes via the utilization of natural elements like zinc (Zn) has been motivated by the discovery of new severe acute respiratory syndrome-related coronavirus 2 (SARS-COV2) variants and the ineffectiveness of certain vaccination treatments during COVID-19 pandemic. In addition, research on SARS-COV-2's viral cellular entry and infection mechanism has shown that it may seriously harm reproductive system cells and impair testicular function in young men and adolescents, which may lead to male infertility over time. In this context, we conducted a narrative review to give an overview of the data pertaining to Zn's critical role in testicular tissue, the therapeutic use of such micronutrients to enhance male fertility, as well as in the potential mitigation of COVID-19, with the ultimate goal of elucidating the hypothesis of the potential use of Zn supplements to prevent the possible harmful effects of SARS-COV2 infection on testis physiological function, and subsequently, on male fertility.

Although the protective effects of zinc against COVID-19 are documented, its impact on COVID-19 vaccine immunogenicity remains unknown.

We conducted a prospective study involving a cohort of 79 Japanese individuals (aged 21-56 years; comprising three subcohorts) and measured their serum zinc levels pre-vaccination and anti-SARS-CoV-2 IgM/IgG levels pre- and post-vaccination over 4 months.

Serum zinc concentrations ranged between 74-140 and 64-113 μg/dL in male and female individuals, respectively, with one male and 11 female participants exhibiting subclinical zinc deficiency (60-80 μg/dL). Mixed models for antibody titers, accounting for the subcohorts, repeat measurements, and covariates (e.g., vaccine type, sex, age, height, steroid use, medical history, smoking and drinking habits, perceived stress, and sleep disturbances) showed positive effects of zinc on IgM (p = 0.012) and IgG (p = 0.013) in 45 female individuals with 255 observations. However, a similar association was not found in the 34 male participants with 162 observations. This discrepancy may be attributed to one participant being included in the subcohort with frequent repeat measurements (10 repeats in 4 months). COVID-19 mRNA vaccine immunogenicity was enhanced in the participants with high baseline blood zinc levels within the reference range.

Our findings underscore the relevance of maintaining adequate zinc levels before vaccination, which can be achieved through a balanced diet and healthy lifestyle choices.

Zinc is a trace element, which plays an important role in many biological processes. The deficiency of zinc will lead to many diseases. Thus, it is of great significance to develop fast and efficient quantitative detection technology for zinc ions. In this study, a novel fluorescence probe FP2 was designed for Zn2+ quantification based on pyrano[3,2-c] carbazole. The structure of FP2 was characterized by 1HNMR, 13CNMR, HRMS, and X-ray diffraction. In the HEPES buffer solution, FP2 is responsive to Zn2+ and greatly enhanced. The pH value and reaction time were investigated, and the optimum reaction conditions were determined as follows: the pH was 7~9 and the reaction time was longer than 24 min. Under the optimized conditions, the concentration of FP2 and Zn2+ showed a good linear relationship in the range of 0~10 μM, and the LOD was 0.0065 μmol/L. In addition, through the 1H NMR titration experiment, density functional theory calculation, and the job plot of FP2 with Zn2+ in the HEPES buffer solution, the binding mode of FP2 and Zn2+ was explained. Finally, the method of flame atomic absorption spectrometry (FAAS) and FP2 were used to detect the content of Zn2+ in the water extract of tea. The results showed that the FP2 method is more accurate than the FAAS method, which shows that the method described in this work could be used to detect the content of Zn2+ in practical samples and verify the practicability of this method.

It has been reported that zinc deficiency is related to severe inflammatory conditions especially those of respiratory diseases. However, studies that have examined the association between the serum zinc concentration and the severity of coronavirus disease 2019 (COVID-19) are still limited. The aim of this study was to assess that association in Japanese inpatients with COVID-19.

This cross-sectional study, conducted from April 2020 to August 2021, included 467 eligible adult inpatients with COVID-19 whose serum zinc concentration was measured. Serum zinc concentration categories were defined as deficiency (< 60 μg/dL), marginal deficiency (≥ 60 to < 80 μg/dL), and normal (≥ 80 μg/dL). Multivariate logistic regression was used to assess the association between serum zinc deficiency and severe COVID-19. Serum zinc concentration levels were compared between mild and other severities of COVID-19 by Dunnett's method. The P for trend was estimated using the Jonckheere-Terpstra test.

The proportions of subjects with serum zinc deficiency (< 60 μg/dL) and marginal zinc deficiency (≥ 60 to < 80 μg/dL) were 39.5% and 54.3% in women, and 36.4% and 57.0% in men, respectively. Serum zinc deficiency was significantly associated with severe COVID-19 compared to marginal deficiency and normal (odds ratio = 3.60, 95% confidence interval = 1.60-8.13, P < 0.01) after adjusting for confounders. An increase in severity of COVID-19 was inversely related to increases in serum zinc concentration levels (P < 0.01 for trend). Each serum zinc concentration of moderate and severe cases was also significantly lower compared with mild cases (P < 0.01).

The severity of COVID-19 was significantly related to serum zinc concentration levels. These results suggest the importance of considering the serum zinc concentration when treating patients with COVID-19.

Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19.

The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders.

Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors.

Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

Background Previous studies have suggested that zinc deficiency (ZD) may increase the risk of short-term mortality in patients with coronavirus disease 2019 (COVID-19). However, the relationship between zinc status and post-acute COVID-19 outcomes remains unclear. This study aimed to determine the association between ZD and long-term outcomes in patients with COVID-19. Methodology We conducted a retrospective cohort study using the TriNetX database, including patients aged 18 years or older diagnosed with COVID-19 between January 1, 2022, and July 31, 2023. Patients had documented serum or plasma zinc levels within three months before COVID-19 diagnosis and were not deceased or hospitalized in the first month of infection. They were categorized into ZD (zinc levels <70 μg/dL) and control (zinc levels ≥70 μg/dL) groups. After 1:1 propensity score matching for demographic and clinical variables, outcomes were assessed from 30 to 180 days post-diagnosis, including all-cause hospitalization, all-cause mortality, and four subphenotypes of post-acute COVID-19. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results After matching, each group included 1,863 patients with balanced baseline characteristics. The ZD group had a higher incidence of all-cause hospitalization (25.3% vs. 20.3%; HR = 1.314; 95% CI = 1.148-1.505; p < 0.001) and all-cause mortality (3.8% vs. 2.2%; HR = 1.735; 95% CI = 1.180-2.551; p = 0.045) compared to the control group during the follow-up period. Among the four subphenotypes, only the cardiac and renal subphenotype showed a significantly higher risk in the ZD group (HR = 1.099; 95% CI = 1.002-1.205; p = 0.004). Conclusions ZD is associated with increased risks of long-term hospitalization, mortality, and increased risk in COVID-19 patients with cardiac and renal comorbidities. Monitoring and managing zinc levels may be important for improving long-term outcomes. Further research is warranted to explore the potential benefits of zinc supplementation in COVID-19 patients with ZD.

SARS-CoV-2 was first discovered in 2019 and has disseminated throughout the globe to pandemic levels, imposing significant health and economic burdens. Although vaccines against SARS-CoV-2 have been developed, their long-term efficacy and specificity have not been determined, and antiviral drugs remain necessary. Flavonoids, which are commonly found in plants, fruits, and vegetables and are part of the human diet, have attracted considerable attention as potential therapeutic agents due to their antiviral and antimicrobial activities and effects on other biological activities, such as inflammation. The present study uses a combination of biochemical, cellular, molecular dynamics, and molecular docking experiments to provide compelling evidence that the flavonoid luteolin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one) has antiviral activity against SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) that is synergistically enhanced by magnesium, zinc, and vitamin C. The IC50 of luteolin against 2 µM 3CLpro is 78 µM and decreases 10-fold to 7.6 µM in the presence of zinc, magnesium, and vitamin C. Thermodynamic stability analyses revealed that luteolin has minimal effects on the structure of 3CLpro, whereas metal ions and vitamin C significantly alter the thermodynamic stability of the protease. Interactome analysis uncovered potential host-virus interactions and functional clusters associated with luteolin activity, supporting the relevance of this flavone for combating SARS-CoV-2 infection. This comprehensive investigation sheds light on luteolin's therapeutic potential and provides insights into its mechanisms of action against SARS-CoV-2. The novel formulation of luteolin, magnesium, zinc, and vitamin C may be an effective avenue for treating COVID-19 patients.

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren's syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.

Independent trials indicate that either oral Zn2+ or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn2+ deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn2+ is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn2+ bioavailability and active absorption by cation transporters known to transport metformin. Intracellular Zn2+ provides a natural buffer of many protease reactions; the variable "set point" is determined by Zn2+ regulation or availability. A Zn2+-interactive protease network is suggested here. The two viral cysteine proteases are therapeutic targets against COVID-19. Viral and many host proteases are submaximally inhibited by exchangeable cell Zn2+. Inhibition of cysteine proteases can improve COVID-19 outcomes and non-infectious inflammation. Metformin reportedly enhances the natural moderating effect of Zn2+ on bioassayed proteome degradation. Firstly, the dissociable metformin-Zn2+ complex could be actively transported by intestinal cation transporters; thereby creating artificial pathways of absorption and increased body Zn2+ content. Secondly, metformin Zn2+ coordination can create a non-natural protease inhibitor independent of cell Zn2+ content. Moderation of peptidolytic reactions by either or both mechanisms could slow (a) viral multiplication (b) viral invasion and (c) the pathogenic host inflammatory response. These combined actions could allow development of acquired immunity to clear the infection before life-threatening inflammation. Nirmatrelvir (Paxlovid®) opposes COVID-19 by selective inhibition the viral main protease by a Zn2+-independent mechanism. Pending safety evaluation, predictable synergistic benefits of metformin and Zn2+, and perhaps metformin/Zn2+/Paxlovid® co-administration should be investigated.

Despite great scientific efforts, understanding the role of COVID-19 clinical biomarkers remains a challenge.

A cross-sectional descriptive study in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. In each place, three groups were formed, made up of 25 patients with COVID-19 in the ICU, 25 hospitalized patients with COVID-19 who did not require the ICU, and 25 healthy subjects as a control group. Five biomarkers were measured: IL-6, hepcidin, ferritin, C-reactive protein, and zinc using ELISA assays.

Ferritin, C-reactive protein, and IL-6 levels were significantly higher in the ICU and non-ICU groups at both study sites. In the case of hepcidin, the levels were significantly higher in the ICU group at both study sites compared to the non-ICU group. Among the groups within each study site, the highest altitude area presented statistically significant differences between its groups in all the markers evaluated. In the lower altitude area, differences were only observed between the groups for the zinc biomarker.

COVID-19 patients residing at high altitudes tend to have higher levels of zinc and IL-6 in all groups studied compared to their lower altitude counterparts.

With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection.

Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen.

There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the circumvallate papillae taste buds (3-35 dpi) and autonomic ganglia (5-35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2-42 dpi).

The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the circumvallate taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Diet is one of the lifestyle factors that is most amenable to intervention, and has a substantial effect on the potential for successful aging and mitigation of the risk of disease. Good nutrition is a pillar of healthy aging, and a large body of evidence attests to the benefits of the Mediterranean diet on the quality of the aging process. The Mediterranean diet comprises a wide range of nutrients which, both individually and collectively, exert positive effects on immunity, in large part mediated by the gut microbiota. In this article, we review the effect of the Mediterranean diet on immunity, and how its beneficial effects are mediated by the gut microbiota. We review the effects of certain key components of the Mediterranean dietary pattern, including vitamins, zinc, selenium, and polyphenols. Overall, the existing body of evidence convincingly demonstrates that the Mediterreanean diet affects immune health by maintaining a healthy body weight and reducing the risk of metabolic and cardiovascular diseases; by reducing inflammation and by promoting a healthy gut microbiota profile.

Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) causing acute systemic disorders and multi-organ damage. β-thalassemia (β-T) is an autosomal recessive disorder leading to the development of anemia. β-T may lead to complications such as immunological disorders, iron overload, oxidative stress, and endocrinopathy. β-T and associated complications may increase the risk of SARS-CoV-2, as inflammatory disturbances and oxidative stress disorders are linked with COVID-19. Therefore, the objective of the present review was to elucidate the potential link between β-T and COVID-19 regarding the underlying comorbidities. The present review showed that most of the β-T patients with COVID-19 revealed mild to moderate clinical features, and β-T may not be linked with Covid-19 severity. Though patients with transfusion-dependent β-T (TDT) develop less COVID-19 severity compared to non-transfusion-depend β-T(NTDT), preclinical and clinical studies are recommended in this regard.

Zinc (Zn) is known for its substantial involvement in the immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels' clinical significance in coronavirus disease (COVID) diagnosis is not yet fully established.

We assessed the association between Zn deficiency, gut integrity, inflammation, and COVID-19 outcomes.

A prospective observational cohort in which plasma Zn, soluble tumor necrosis factor alpha receptor II (sTNF-RII) intestinal fatty-acid binding protein (IFABP; marker of intestinal integrity), and zonulin levels (intestinal permeability) were collected from participants during the acute phase of a confirmed COVID-19 diagnosis. Zn was modeled as continuous and binary, categorized as Zn deficiency (Zn < 75 μg/dL) and Zn sufficiency (Zn ≥ 75 μg/dL). COVID-19 outcomes were classified according to the World Health Organization clinical progression scale. We used cumulative probit regression to assess if suboptimal Zn levels, gut, and inflammatory markers increase the likelihood of worse COVID-19 outcomes.

Zn deficiency was independently associated with 63% higher predicted odds of worse COVID outcomes. Increases in sTNF-RII {unadjusted odds ratio (uOR): 3.43 [95% confidence interval (CI): 2.02, 5.82]} and zonulin [uOR: 1.83 (95% CI: 1.21, 2.76)] levels were associated with greater odds of worse COVID outcomes. IFABP was not associated with worse COVID outcomes [uOR: 1.12 (95% CI: 0.82, 1.53)] or acute Zn deficiency [uOR: 1.35 (95% CI: 0.79, 2.35)]. The adjusted predicted odds of worse COVID outcomes are 3-fold higher (P = 0.04) for every one-unit decrease in Zn and is more than 2 times greater odds of COVID severity (P = 0.01) for every 1-unit increase in sTNF-RII.

Zn deficiency and inflammation were independently associated with greater odds of worse COVID outcomes.

Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic effect of SARS-CoV-2 virus protein on IFN. Additionally, Zn has been found to promote the proliferation and differentiation of T and B lymphocytes, thereby improving immune function, inhibiting RNA-dependent RNA polymerase (RdRp) in SARS- CoV-2 reducing the viral replication and stabilizing the cell membrane by preventing the proteolytic processing of viral polyprotein and proteases enzymes. Interestingly, Zn deficiency has been correlated with enhanced SARS-CoV-2 viral entry through interaction between the ACE2 receptor and viral spike protein. Along with zinc, Cu possesses strong virucidal capabilities and is known to be effective at neutralizing a variety of infectious viruses, including the poliovirus, influenza virus, HIV type 1, and other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Cu-related antiviral action has been linked to different pathways. First, it may result in permanent damage to the viral membrane, envelopes, and genetic material of viruses. Second, Cu produces reactive oxygen species to take advantage of the redox signaling mechanism to eradicate the virus. The present review focused on Zn and Cu in the treatment and prevention of viral infection. Moreover, the application of metals such as Cu and gold in nanotechnology for the development of antiviral therapies and vaccines has been also discussed.

The aim of this study was to determine the association between dietary mineral intake and Coronavirus-disease 2019 (COVID-19) infection and its associated hospitalization.

This cohort study utilized the MASHAD study population, which comprised individuals aged 35-65. Upon recruitment in 2007, dietary intake was documented using a validated 65-item food frequency questionnaire (FFQ). Data on COVID-19 PCR test results was collected from all relevant medical centers in Mashhad between February 2020 and June 2022. The regression model included dietary minerals and employed the backward variable selection method, along with advanced data analysis techniques.

The final analysis involved 1957 participants, including 193 COVID-19-positive patients. The mean age was 49.71 and 50.28 years in the COVID-19-positive and negative groups, respectively (p = 0.12). Dietary intakes of magnesium, iron, and potassium were notably lower in COVID-19-positive patients (P < 0.05). Following adjustments for age and sex, dietary iron remained significantly associated with COVID-19 incidence (OR = 0.94, 95% CI: 0.90-0.98). Furthermore, a statistically significant relationship was observed between dietary zinc and hospitalization due to COVID-19 (OR = 0.69, 95% CI: 0.51-0.93). In dynamical system models, intakes of calcium, zinc, and iron below the cut-offs of 1138, 9.7, and 8.17 mg/day, respectively, were linked to an increased risk of COVID-19 incidence.

Higher dietary iron and zinc intake are associated with decreased risk of COVID-19 infection and hospitalization, respectively.

The zinc complexes of chloroquine (CQ; [Zn(CQH+)Cl3]) and hydroxychloroquine (HO-CQ; [Zn(HO-CQH+)Cl3]) were synthesized and characterized by X-Ray structure analysis, FT-IR, NMR, UV-Vis spectroscopy, and cryo-spray mass spectrometry in solid state as well as in aqueous and organic solvent solutions, respectively. In acetonitrile, up to two Zn2+ ions bind to CQ and HO-CQ through the tertiary amine and aromatic nitrogen atoms (KN-aminCQ = (3.8 ± 0.5) x 104 M-1 and KN-aromCQ = (9.0 ± 0.7) x 103 M-1 for CQ, and KN-aminHO-CQ = (3.3 ± 0.4) x 104 M-1 and KN-aromHO-CQ = (1.6 ± 0.2) x 103 M-1 for HO-CQ). In MOPS buffer (pH 7.4) the coordination proceeds through the partially deprotonated aromatic nitrogen, with the corresponding equilibrium constants of KN-arom(aq)CQ = (3.9 ± 1.9) x 103 M-1and KN-arom(aq)HO-CQ = (0.7 + 0.4) x 103 M-1 for CQ and HO-CQ, respectively. An apparent partition coefficient of 0.22 was found for [Zn(CQH+)Cl3]. Mouse embryonic fibroblast (MEF) cells were treated with pre-synthesized [Zn((HO-)CQH+)Cl3] complexes and corresponding ZnCl2/(HO-)CQ mixtures and zinc uptake was determined by application of the fluorescence probe and ICP-OES measurements. Administration of pre-synthesized complexes led to higher total zinc levels than those obtained upon administration of the related zinc/(hydroxy)chloroquine mixtures. The differences in the zinc uptake between these two types of formulations were discussed in terms of different speciation and character of the complexes. The obtained results suggest that intact zinc complexes may exhibit biological effects distinct from that of the related zinc/ligand mixtures.

Zinc (Zn) is one of the most important trace elements in the human body and plays a key role in various physiological processes, especially in bone metabolism. Zn-containing materials have been reported to enhance bone repair through promoting cell proliferation, osteogenic activity, angiogenesis, and inhibiting osteoclast differentiation. Therefore, Zn-based biomaterials are potential substitutes for traditional bone grafts. In this review, the specific mechanisms of bone formation promotion by Zn-based biomaterials were discussed, and recent developments in their application in bone tissue engineering were summarized. Moreover, the challenges and perspectives of Zn-based biomaterials were concluded, revealing their attractive potential and development directions in the future.

Metals and metalloids are known for their nutritional as well as toxic effects in humans. In the context of the SARS-CoV-2 pandemic, understanding the role of metals on COVID-19 infection is becoming important due to their role in infectious diseases. During the past 2 years, a significant number of studies have examined the impact of metals and metalloids on COVID-19 morbidity and mortality. We conducted a systematic review of peer-reviewed manuscripts on the association of metals and metalloids with SARS-CoV-2 infection and COVID-19 severity published since the onset of the pandemic.

We searched for epidemiological studies available through the PubMed database published from January 2020 to December 2022. Of 92 studies identified, 20 met our inclusion criteria. These articles investigated the association of zinc (Zn), iron (Fe), selenium (Se), manganese (Mn), cadmium (Cd), arsenic (As), copper (Cu), magnesium (Mg), chromium (Cr), and/or lead (Pb) levels on SARS-CoV-2 infection and/or COVID-19 severity. Of the ten metals and metalloids of interest that reported either positive, negative, or no associations, Zn yielded the highest number of articles (n = 13), followed by epidemiological studies on Se (n = 7) and Fe (n = 5). Elevated serum Zn and Se were associated with reduced COVID-19 severity and mortality. Similarly, higher levels of serum Fe were associated with lower levels of cellular damage and symptoms of SARS-CoV-2 infection and with faster recovery from COVID-19. On the other hand, higher serum and urinary Cu and serum Mg levels were associated with higher COVID-19 severity and mortality. Along with the positive or negative effects, some studies reported no impact of metals on SARS-CoV-2 infection. This systematic review suggests that metals, particularly Zn, Fe, and Se, may help reduce the severity of COVID-19, while Cu and Mg may aggravate it. Our review suggests that future pandemic mitigation strategies may evaluate the role of Zn, Se, and Fe as potential therapeutic interventions.

It is proven that the blood concentration of antioxidants can impress the severity of viral infections, including COVID-19. However, the lack of a comprehensive study accumulating existing data regarding COVID-19 can be perceived. Therefore, this systematic review is aimed to report the association between the blood concentration of several antioxidants and the overall health condition of COVID-19 patients. We summarized the available data surrounding the serum antioxidant level in COVID-19 patients and COVID-19 outcomes. A systematic search was performed in PubMed, Scopus, Web of Science, and Cochrane, and studies that evaluated the association between antioxidants and COVID-19 outcomes were included. Of 4101 articles that were viewed in the database search, 38 articles were included after the title, abstract, and full-text review. Twenty-nine studies indicated that lower serum antioxidants are associated with worse outcomes, and one study reported no association between serum zinc (Zn) level and COVID-19 outcomes. In most cases, antioxidant deficiency was associated with high inflammatory factors, high mortality, acute kidney injury, thrombosis, intensive care unit (ICU) admission, acute respiratory distress syndrome, cardiac injury, and the need for mechanical ventilation (MV), and there was no significant association between serum antioxidants level and ICU or hospital length of stay (LOS). It seems that higher levels of antioxidants in COVID-19 patients may be beneficial to prevent disease progression. However, clinical trials are needed to confirm this conclusion.

Considering the anti-viral effects of Spirulina platensis (Sp), this study investigated the impact of Sp on impaired blood biomarkers of patients hospitalized in the intensive care unit (ICU) with COVID-19. Therefore, 104 patients (aged 48-66; 61.5% male) were randomly assigned to the Sp (daily consumption of 5 g) or placebo group for 2 weeks. Linear regression analysis was employed to assess the differences in blood test results between the control and intervention groups among patients with COVID-19. Our results showed significant differences in certain hematological tests, including a higher level of hematocrit (HCT) and a lower platelet count (PLT) in the intervention group (p < 0.05). The percentage of lymphocytes (Lym%) in serology testing was significantly different between the control and intervention groups (p = 0.03). In terms of biochemical test analyses, Sp supplementation was associated with reduced levels of both blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) (p = 0.01). Furthermore, on day 14, the intervention group displayed significantly higher medians of serum protein, albumin, and zinc compared to the control group (p < 0.05). Additionally, patients supplemented with Sp had a lower BUN-albumin ratio (BAR) (p = 0.01). No immunological and hormonal differences were observed between groups following 2 weeks. Our analysis indicates that Sp supplementation may be effective in regulating some blood test abnormalities associated with COVID-19. This study was registered at ISRCTN as IRCT20200720048139N1.

Tryptic hydrolysates of protein fractions obtained by the Osborne method from chickpea (Cicer arietinum L.) seeds interacted with zinc ions and the results of chelation were monitored by the Energy Dispersive X-Ray (EDX) technique. The glutelin hydrolysate (GluHyd) reacted with zinc ions and depicted a relatively higher zinc content. For this reason, the zinc complex of the glutelin hydrolysate (GluHyd-Zn) was studied deeper, and 11 peptides were identified in its more zinc-containing second fraction obtained after gel filtration. The peptide HKERVQLHIIPTAVGK showed a relatively higher chelating capacity (57.86 ± 2.14%). According to the result of the ICP-OS analysis, 1 mg peptide could chelate 381.61 ± 133.39 µg zinc, and the molar ratio of peptide-zinc was about 1:4. Spectral methods proved that side chain and C-termini carboxyl groups of the peptide mostly were involved in chelation and N atoms of amino side chains, imidazole group of histidine, and N-termini at some extents were occupied by the metal ions. Modeling of zinc-peptide interaction was done using Molecular Operating Environment (MOE) software. The results of the docking correlate with the experimental data.ACE2 inhibitory effect of HKERVQLHIIPTAVGK-Zn complex (IC50 = 1.5 mg/mL) was better than that of HKERVQLHIIPTAVGK (IC50 = 2.2 mg/mL).

Zinc is a multipurpose trace element for the human body, as it plays a crucial part in various physiological processes, such as cell growth and development, metabolism, cognitive, reproductive, and immune system function. Its significance in human health is widely acknowledged, and this has led the scientific community towards more research that aims to uncover all of its beneficial properties, especially when compared to other essential metal ions. One notable area where zinc has shown beneficial effects is in the prevention and treatment of various diseases, including cancer. This review aims to explain the involvement of zinc in specific health conditions such as cancer, coronavirus disease 2019 (COVID-19) and neurological disorders like Alzheimer's disease, as well as its impact on the gut microbiome.

Over the last 20 years, the use of dietary supplements (DS) has continued to grow in many countries. Due to the public health crisis brought on by the COVID-19 pandemic and amidst fears regarding COVID-19 vaccines and their low supply in many regions of the world, there has been a marked interest in the use of DS as alternative means of protecting against and treating this emerging disease, as well as boosting the immune system and minimizing the risk of inflammation. Despite a lack of evidence to suggest their efficacy, a surge in the sales of DS has been reported in many parts of the world. Questions have also been raised about the health effects associated with DS due to their increased use during the health crisis. Numerous scientific studies have demonstrated their beneficial properties as well as some adverse and even toxic effects. In addition, given the current global interest in this issue, a review is needed to establish the status of dietary supplements before and during the health crisis. The aim of this review is to summarize the current evidence on the impact of dietary supplements on the incidence of the COVID-19 pandemic, as well as their regulation and associated market trends. First, we provide an overview of DS, including a comprehensive review of the legislative and regulatory aspects of DS in the USA, China, the EU, and Algeria. Second, we describe the prevalence of the most commonly consumed DS and their efficacy as a prophylactic modality in the era of COVID-19. Additionally, we examine the structure and size of the DS market in the countries that predominantly produce and import them, its global market trend, and the impact of the COVID-19 pandemic on market growth. Finally, in this review, we also discuss the profile of DS users.

Men and women exhibit different presentations in COVID-19. Changes in zinc finger domains in X chromosome causes disorders of sex development. So, we aimed to evaluate sex distinctions regarding serum zinc in severe COVID-19.

Data from electronic records of severe COVID-19 patients were correlated with serum zinc. Logistic regression investigated predictors and protectors of hypozincemia in men and women.

We assessed 188 medical records (men = 114, women = 74). Men correlated low zinc with hypertension (cc = 0.303, p < 0.001), diabetes (cc = 0.198, p = 0.031), hemoglobin (cc = -0.258, p = 0.005), and albumin (cc = -0.219, p = 0.027). Low lymphocyte count (cc = 0.315, p = 0.005), C-reactive protein (cc = -0.248, p = 0.037), and enteral nutrition (cc = 0.269, p = 0.016) were correlated with hypozincemia in women. Age correlated with low zinc in men (c = -0.304, p = 0.001) and women (cc = -0.298, p = 0.010). In men, hypertension (OR = 4.905, p = 0.005) and lymphopenia (OR = -0.999, p = 0.019) were low zinc predictors, while lung injury > 50% was a protective factor (OR = -0.280, p = 0.025). Lymphopenia (OR = -0.999, p = 0.005) and difficult weaning from mechanical ventilation (MV) (OR = 4.359, p = 0.036) were predictors of hypozincemia in women. Difficult weaning from MV (OR = 3.012, p = 0.003) and age (OR = 1.038, p = 0.002) were hypozincemia predictors regardless sex.

Hypertension, diabetes, hemoglobin and albumin were correlated with low zinc in men. Lymphopenia, reactive-C protein and enteral nutrition were correlated with low zinc in women. In men, hypertension and low lymphocytes were predictors of hypozincemia. Lymphopenia and difficult weaning from MV were predictors of low zinc in women.

The spike protein (S) of SARS-CoV-2 is able to bind to the human angiotensin-converting enzyme 2 (ACE2) receptor with a much higher affinity compared to other coronaviruses. The binding interface between the ACE2 receptor and the spike protein plays a critical role in the entry mechanism of the SARS-CoV-2 virus. There are specific amino acids involved in the interaction between the S protein and the ACE2 receptor. This specificity is critical for the virus to establish a systemic infection and cause COVID-19 disease. In the ACE2 receptor, the largest number of amino acids playing a crucial role in the mechanism of interaction and recognition with the S protein is located in the C-terminal part, which represents the main binding region between ACE2 and S. This fragment is abundant in coordination residues such as aspartates, glutamates, and histidine that could be targeted by metal ions. Zn²⁺ ions bind to the ACE2 receptor in its catalytic site and modulate its activity, but it could also contribute to the structural stability of the entire protein. The ability of the human ACE2 receptor to coordinate metal ions, such as Zn²⁺, in the same region where it binds to the S protein could have a crucial impact on the mechanism of recognition and interaction of ACE2-S, with consequences on their binding affinity that deserve to be investigated. To test this possibility, this study aims to characterize the coordination ability of Zn²⁺, and also Cu²⁺ for comparison, with selected peptide models of the ACE2 binding interface using spectroscopic and potentiometric techniques.

Since the coronavirus disease 2019 (COVID-19) pandemic appeared, both governments and the scientific community have focused their efforts on the search for prophylactic and therapeutic alternatives in order to reduce its effects. Vaccines against SARS-CoV-2 have been approved and administered, playing a key role in the overcoming of this situation. However, they have not reached the whole world population, and several doses will be needed in the future in order to successfully protect individuals. The disease is still here, so other strategies should be explored with the aim of supporting the immune system before and during the infection. An adequate diet is certainly associated with an optimal inflammatory and oxidative stress status, as poor levels of different nutrients could be related to altered immune responses and, consequently, an augmented susceptibility to infections and severe outcomes derived from them. Minerals exert a wide range of immune-modulatory, anti-inflammatory, antimicrobial, and antioxidant activities, which may be useful for fighting this illness. Although they cannot be considered as a definitive therapeutic solution, the available evidence to date, obtained from studies on similar respiratory diseases, might reflect the rationality of deeper investigations of the use of minerals during this pandemic.

Some micronutrients have key roles in immune defence, including mucosal defence mechanisms and immunoglobulin production. Altered micronutrient status has been linked with COVID-19 infection and disease severity. We assessed the associations of selected circulating micronutrients with anti-SARS-CoV-2 IgG and IgA seropositivity in the Swiss community using early pandemic data.