Micronutrients, genetics and COVID-19.

PURPOSE OF REVIEW: Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. RECENT FINDINGS: In patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor ( VDR ) gene, most notably rs2228570 (FokI) "f" allele and rs7975232 (ApaI) "aa" genotype as poor prognostic markers. SUMMARY: Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.

Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2: A narrative review.

BACKGROUND: COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. METHODS: We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. RESULTS: Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. CONCLUSION: There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Antibodies to SARS-CoV-2 in follicular fluids and their association with assisted reproduction.

Introduction: Every second woman suffering from infertility asks for medical help. There is public concern that vaccination-induced antibodies (Ab) are negatively associated with fertility. A recent study has demonstrated an association between SARS-CoV-2 vaccination and a lower pregnancy rate in the subsequent 60 days. Consequently, Ab could affect fertility success in assisted reproduction. Methods: To address this question, we compared fertilization outcomes of vaccinated (n=35) and nonvaccinated (n=34) women. Paired serum samples and multiple follicular fluids (FF) (up to 10 from the same donor) were collected during the course of assisted reproduction and characterized for oocyte quality, the presence of Ab and trace element concentrations. Results: The results showed a positive correlation of vaccination-induced neutralizing activity of SARS-CoV-2-Ab in serum and FF. On average, Ab concentrations in serum were higher than in the corresponding FF. However, wide variations in SARS-CoV-2 Ab titers were observed between different FF, correlating to trace element levels, even when retrieved from the same donor. Discussion: Overall, FF contents are highly variable, but no negative association was observed between Ab in serum or FF and fertilization success and oocyte development, supporting the safety of SARS-CoV-2 vaccination during assisted reproduction.

Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.

The concentrations of essential/toxic elements in serum of COVID-19 patients are not directly related to the severity of the disease.

BACKGROUND: In recent months, the current COVID-19 pandemic has generated thousands of studies directly or indirectly related with this disease and/or the coronavirus SARS-CoV-2 causing the infection. On August 22, 2022, the database PUBMED included 287,639 publications containing the term COVID-19. However, in spite of the importance of trace elements in human health, including the immune system, data on the levels of metals/metalloids in COVID-19 patients is very limited. METHODS: The concentrations of As, Cd, Cr, Cu, Hg, Fe, Mg, Mn, Pb, Se, V and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 126 serum samples of individuals infected with SARS-CoV-2, as well as in 88 samples of non-infected individuals. Participants were divided into four groups: i) individuals COVID-19 positive (COVID-19 +) with an asymptomatic infection course; ii) individuals suffering mild COVID-19; iii) individuals suffering severe COVID-19, and iv) individuals COVID-19 negative (COVID-19-) (control group). The occurrence of the analyzed metals/metalloids was evaluated along with the biochemical profile, including blood cell counts, lipids, proteins and crucial enzymes. RESULTS: Serum levels of Mg, V, Cr, Cu, Cd, and Pb were higher in COVID-19 positive patients than those in the control group. Although no significant differences were observed between the different groups of patients, the concentrations of Cd, Pb, V and Zn showed a tendency to be higher in individuals with severe COVID-19 than in those showing mild symptoms or being asymptomatic. Arsenic and Hg were rarely detected, regardless if the subjects were infected by SARS-CoV-2, or not. The current results did not show significant differences in the levels of the rest of analyzed elements according to the severity of the disease (asymptomatic, mild and severe). CONCLUSIONS: In spite of the results here obtained, we highlight the need to reduce the exposure to Cd, Pb and V to minimize the potential adverse health outcomes after COVID-19 infection. On the other hand, although a protective role of essential elements was not found, Mg and Cu concentrations were higher in severe COVID-19 patients than in non-infected individuals.

Impact of the SARS-CoV-2 lockdown measures in Southern Spain on PM10 trace element and gaseous pollutant concentrations.

Trace element concentrations within PM10, gaseous pollutants (NO2 and SO2), and PM10 levels were studied during the Covid-19 lockdown at a regional level in Southern Spain (Andalusia). Pollutant concentrations were compared considering different mobility periods (pre-lockdown, lockdown, and relaxation) in 2020 and previous years (2013-2016). An acute decrease in NO2 levels (<50%) was observed as a consequence of traffic diminution during the confinement period. Moreover, a lower reduction in PM10 levels and a non-clear pattern for SO2 levels were observed. During the lockdown period, PM10 elements released from traffic emissions (Sn and Sb) showed the highest concentration diminution in the study area. Regarding the primary industrial sites, there were no significant differences in V, Ni, La, and Cr concentration reduction during 2020 associated with industrial activity (stainless steel and oil refinery) in Algeciras Bay. Similarly, concentrations of Zn showed the same behaviour at Cordoba, indicating that the Zn-smelter activity was not affected by the lockdown. Nevertheless, stronger reductions of Cu, Zn, and As in Huelva during the confinement period indicated a decrease in the nearby Cu-smelter emissions. Brick factories in Bailen were also influenced by the confinement measures, as corroborated by the marked decrease in concentrations of Ni, V, Cu, and Zn during the lockdown compared to that from previous years. This work has shown the baseline concentrations of trace elements of PM10, which is of great value to air quality managers in order to minimise pollution levels by applying the confinement of the population, affecting both traffic and industrial anthropogenic activities.

The effect of zinc supplementation on the course of COVID-19 - A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The aim of the study was to determine the antiviral effect of the administration of zinc in COVID-19 patients. MATERIAL AND METHODS: A literature search was performed in P Web of Science, PubMed, Scopus and Cochrane databases from 1 January 2020 - 22 August 2022. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies. RESULTS: A total of 9 eligible studies were identified. In-hospital mortality in zinc supplementation patients, and patients treated without zinc, varied and amounted to 21.6% vs. 23.04% difference (OR=0.71; 95%CI: 0.62-0.81; p<0.001). 28-day to 30-day mortality in patients treated with zinc was 7.7%, compared to 11.9% for patients treated without zinc (OR=0.61; 95%CI: 0.35-1.06; p=0.08). In-hospital adverse events among patients treated with and without COVID-19 did not show any statistically significant differences in relation to acute kidney injury occurrence (12.8% vs. 12.4%, respectively; OR=0.63; 95%CI: 0.19-2.12; p=0.45, as well as need for mechanical ventilation (13.2% vs. 14.1%; OR=0.83; 95%CI: 0.52-1.32; p=0.43). CONCLUSIONS: Zinc supplementation is associated with lower COVID-19 in-hospital mortality. Additionally, it is risk-free in COVID-19 patients since there have been no negative side effects, such as acute renal damage or the requirement for mechanical ventilation compared to patients without COVID-19. Due to scientific evidence and the role it represents in the human body, zinc supplementation should be taken into consideration for COVID-19 patients as an adjunct therapy.

Association of Serum Zinc and Inflammatory Markers with the Severity of COVID-19 Infection in Adult Patients.

COVID-19 infection can spread in the host body without any adequate immune response. Zinc is an essential trace element with strong immunoregulatory and antiviral properties and its deficiency might lead to inflammation and oxidative stress. The aim of the current study was to determine the association of serum zinc and inflammatory markers with the severity of COVID-19 infection. This was a prospective observational study in which 123 COVID-19-positive adult patients and 48 controls were recruited. The initial comparative analysis was conducted between COVID-19 patients and controls. COVID-19-positive patients were further divided into three different groups (mild, moderate, and severe) based on the severity of COVID-19 infection. COVID-19 patients showed significantly lower serum zinc levels (8.8 ± 2.3 µmol/L) compared to healthy controls (11.9 ± 1.8 µmol/L). There was a negative correlation between serum zinc levels and the severity of COVID-19 infection (r = −0.584, p < 0.0001) and this effect was independent of age (r = −0.361, p < 0.0001). Furthermore, inflammatory markers showed a positive correlation with the severity of COVID-19 infection and a negative correlation with the levels of serum zinc. The study demonstrated an association between COVID-19 infection with low serum zinc levels and elevated inflammatory markers. Further studies to assess the significance of this observation are needed, which may justify zinc supplementation to mitigate the severity of COVID-19 infection.

Zinc in Human Health and Infectious Diseases.

During the last few decades, the micronutrient zinc has proven to be an important metal ion for a well-functioning immune system, and thus also for a suitable immune defense. Nowadays, it is known that the main cause of zinc deficiency is malnutrition. In particular, vulnerable populations, such as the elderly in Western countries and children in developing countries, are often affected. However, sufficient zinc intake and homeostasis is essential for a healthy life, as it is known that zinc deficiency is associated with a multitude of immune disorders such as metabolic and chronic diseases, as well as infectious diseases such as respiratory infections, malaria, HIV, or tuberculosis. Moreover, the modulation of the proinflammatory immune response and oxidative stress is well described. The anti-inflammatory and antioxidant properties of zinc have been known for a long time, but are not comprehensively researched and understood yet. Therefore, this review highlights the current molecular mechanisms underlying the development of a pro-/ and anti-inflammatory immune response as a result of zinc deficiency and zinc supplementation. Additionally, we emphasize the potential of zinc as a preventive and therapeutic agent, alone or in combination with other strategies, that could ameliorate infectious diseases.

Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe.

Introduction: Certain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe. Methods: Serum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory. Results: Median levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769). Discussion: The data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.

Serum trace elements levels and clinical outcomes among Iranian COVID-19 patients.

OBJECTIVES: The relationship between immunity and trace elements levels is well known. We aimed to estimate the association of serum trace elements with severity and outcomes in the Coronavirus Disease-2019 (COVID-19) patients. METHODS: In this single-centered, prospective, observational study, we enrolled 114 patients admitted to severe intensive care units (ICUs) and corresponding 112 sex and aged-matched non-ICU ward patients. Demographic data, clinical characteristics, and outcomes were all collected. We analyzed serum levels of zinc (Zn), copper (Cu), selenium (Se), and manganese (Mn) in both severity groups. RESULTS: The serum levels of Cu, Se, and Mn in both groups were within the normal range while Zn serum levels were lower than normal values. Based on these findings, Zn, Cu, Se, and Mn serum levels were not associated with disease severity (P > 0.05), while we found Zn serum levels were strongly associated with patient outcomes (P = 0.005). Our results indicated lower Mn serum levels were associated with age more than 55 years (P= 0.006). Our results were not in favor of a causal relationship between serum trace elements levels and disease severity. CONCLUSION: We found Zn level to be a strong indicator for patients' outcomes that can be considered for monitoring patient prognosis. Nutritional measures or supplementation can help reduce poor outcomes caused by low Zn levels in Iranian COVID-19 patients.

Evaluation of the Relationship Between Aquaporin-1, Hepcidin, Zinc, Copper, and Iron Levels and Oxidative Stress in the Serum of Critically Ill Patients with COVID-19.

Our study aims to determine the relationship between hepcidin, aquaporin (AQP-1), copper (Cu), zinc (Zn), iron (Fe) levels, and oxidative stress in the sera of seriously ill COVID-19 patients with invasive mechanical ventilation. Ninety persons with and without COVID-19 were taken up and separated into two groups. The first group included seriously COVID-19 inpatients having endotracheal intubation in the intensive care unit (n = 45). The second group included individuals who had negative PCR tests and had no chronic disease (the healthy control group n = 45). AQP-1, hepcidin, Zn, Cu, Fe, total antioxidant status (TAS), and total oxidant status (TOS) were studied in the sera of both groups, and the relations of these levels with oxidative stress were determined. When the COVID-19 patient and the control groups were compared, all studied parameters were found to be statistically significant (p < 0.01). Total oxidant status (TOS), oxidative stress index (OSI), and AQP-1, hepcidin, and Cu levels were increased in patients with COVID-19 compared to healthy people. Serum TAC, Zn, and Fe levels were found to be lower in the patient group than in the control group. Significant correlations were detected between the studied parameters in COVID-19 patients. Results indicated that oxidative stress may play an important role in viral infection due to SARS-CoV-2. We think that oxidative stress parameters as well as some trace elements at the onset of COVID-19 disease will provide a better triage in terms of disease severity.

Micronutrient deficiency risk in long-term enterally fed patients: A systematic review.

BACKGROUND AND AIMS: The micronutrient status of those receiving long-term enteral nutrition (EN) is poorly characterised. This systematic review was undertaken to determine prevalence of micronutrient deficiency in those receiving EN; the impact of the route of feeding; whether underlying disease or clinical factors were associated with micronutrient status; and the efficacy of interventions utilised to treat identified micronutrient deficiency. METHODS: Electronic databases (CINAHL, Embase, PubMed, Web of Science) were searched to June 2021 for publications of primary investigation of micronutrient status in adults or children (>5yrs) receiving EN for >2 months in their usual residence. Independent assessment of compliance with inclusion criteria (Covidence®), data extraction of predefined data points, assessment of basis (Academy of Dietetics Quality Checklist) and certainty of evidence (GRADE) was assessed by at least two authors. (PROSPERO Registration: CRD42021261113). RESULTS: Thirty-one studies (n = 744) met inclusion criteria. Deficiency was reported for copper, zinc, selenium, beta-carotene, and vitamins A, D and E: Only copper, zinc and selenium were associated with physical/haematological manifestations of deficiency. Jejunal feeding was associated with the development of copper deficiency and often required gastric or parenteral replacement to resolve the issue. Circumstances leading to deficiency included receiving feed products formulated with inadequate amounts of the implicated nutrient, low feed product volumes in the context of low macronutrient requirements, and nutritional decline prior to commencement of EN. Potential confounding factors such as inflammation were rarely accounted for. No studies investigated the contribution of underlying clinical condition on micronutrient status, and no other clinical or demographic features appeared to impact outcomes. Reported methods for treating identified deficiencies were usually successful in reversing deficiency symptoms. The certainty of evidence is very low, and the level of bias moderate to high. CONCLUSION: While the evidence is very uncertain about the effect of long-term enteral feeding on the development of micronutrient deficiencies, clinicians should be alert to the possibility of micronutrient deficiency developing in long-term EN fed patients. Those who may be at increased risk are those receiving nutrition into the jejunum, those who meet macronutrient requirements in low volumes of EN product, and those commencing EN in a nutritionally deplete state. Further research and surveillance of micronutrient status with contemporary EN products and practices is required.

A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels.

BACKGROUND: Although essential trace elements (ETEs) play pivotal roles in life-supporting biochemical processes, their function in innate and adaptive immunity has not been fully elucidated, particularly during immunization. Furthermore, the association between anti-SARS-CoV-2 specific IgG antibodies and ETE levels with vaccine responsiveness has not been investigated. METHODS: The present study explored the status of ETEs (Mn, Cu, Zn, and Se) in sera of healthy women before and after vaccination with the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in a follow-up period of six months. The main aim was to explore links between ETE levels and IgG antibodies produced against Spike glycoprotein's Receptor-Binding Domain (RBD). RESULTS: A recombinant protein of SARS-CoV-2 comprising the receptor binding domain was successfully expressed in HEK-293 T cells. The purified protein was suitable for producing a sensitive antibody detection assay for human serum and monitored seropositivity, indicating a transient response with peak anti-SARS-CoV-2 IgG levels 2 months after vaccination. In parallel to increasing antibody titers, serum concentrations of Cu, Mn, and Se were not affected by vaccination, and concentrations remained relatively constant at the different sampling times during the 6-month observation period. Total serum Zn concentrations were slightly elevated when compared between the first and last sampling dates. Overall, no consistent effects of vaccination on any of the three trace elements analyzed in our study were observed. CONCLUSION: Vaccination of adult healthy female volunteers with an mRNA vaccine was not associated with consistent changes in serum trace element concentrations over a six-month observation period.

Association of iron-related biomarkers with severity and mortality in COVID-19 patients.

BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

Review of nutritional components in Covid-19: what about micronutrients? / Revue des facteurs nutritionnels dans la Covid-19 : qu'en est-il des micronutriments ?

Nutritional status is an important protection factor against viral infections. Both undernutrition and malnutrition cause deficits in micronutrients, trace elements and vitamins necessary for various physiological functions and the appropriate functioning of the immune system. These deficiencies and infectious diseases often coexist, with complex interactions. An assessment of the micro-nutrient nutritional status of Covid-19 patients has not been at the center of priorities and recommendations, due to both the medical emergency and the absence of direct evidence and rapid effects of supplementation. Few recommendations have come from learned societies due to the lack of significant evidence of the effects of supplementation in positive patients and a need for robust studies. Essential trace elements and vitamins are necessary for the differentiation, activation and execution of many functions of immune cells, but their specific role has yet to be defined. This review article discusses in the context of Covid-19 the importance of micronutrients (selenium, copper, zinc, vitamins C, D, A and those of group B) in the host to tend towards an optimization of the immune response to infections. A nutritional balance remains the key word for achieving micronutrient homeostasis. Attention had to be paid to micronutrients in primary prevention, in the general population, in order to reduce the risk of impaired nutritional status in case of major health situations.

Le statut nutritionnel est important pour protéger des infections virales. La dénutrition comme la malnutrition induisent des déficits en micronutriments, éléments-trace et vitamines nécessaires aux fonctions physiologiques et au fonctionnement du système immunitaire. Ces carences et les maladies infectieuses coexistent souvent en complexes interactions. Une évaluation de l'état nutritionnel en micronutriments des patients Covid-19 n'a pas été au centre des priorités face à l'urgence médicale et à l'absence de preuves directes et rapides des effets de supplémentation. Peu de recommandations ont émané des sociétés savantes par manque de preuves significatives des effets de supplémentations, avec une nécessité d'études robustes. S'il est reconnu que les oligo-éléments essentiels et les vitamines sont nécessaires à la différenciation, l'activation et l'exécution de fonctions des cellules immunitaires, leur rôle spécifique reste encore à définir. Cette synthèse aborde dans la Covid-19 l'importance des micronutriments (sélénium, cuivre, zinc, vitamines C, D, A et groupe B) chez l'hôte pour tendre vers une optimisation de la réponse immunitaire aux infections. En prévention primaire, en population générale, un équilibre nutritionnel reste central pour atteindre l'homéostasie des micronutriments, pour diminuer le risque des situations de déséquilibre et de fragilisation face à des situations sanitaires d'ampleur.

The Mutual Relationship among Cardiovascular Diseases and COVID-19: Focus on Micronutrients Imbalance.

Micronutrients are ions and vitamins humbly required by the human body. They play a main role in several physiological mechanisms and their imbalance is strongly associated with potentially-fatal complications. Micronutrient imbalance is associated with many cardiovascular diseases, such as arrythmias, heart failure, and ischemic heart disease. It has been also observed in coronavirus disease 2019 (COVID-19), particularly in most severe patients. The relationship between cardiovascular diseases and COVID-19 is mutual: the latter triggers cardiovascular disease onset and worsening while patients with previous cardiovascular disease may develop a more severe form of COVID-19. In addition to the well-known pathophysiological mechanisms binding COVID-19 and cardiovascular diseases together, increasing importance is being given to the impact of micronutrient alterations, often present during COVID-19 and able to affect the balance responsible for a good functioning of the cardiovascular system. In particular, hypokalemia, hypomagnesemia, hyponatremia, and hypocalcemia are strongly associated with worse outcome, while vitamin A and D deficiency are associated with thromboembolic events in COVID-19. Thus, considering how frequent the cardiovascular involvement is in patients with COVID-19, and how it majorly affects their prognosis, this manuscript provides a comprehensive review on the role of micronutrient imbalance in the interconnection between COVID-19 and cardiovascular diseases.

Association of trace element status in COVID-19 patients with disease severity.

Caused by the new SARS-CoV-2 coronavirus, COVID-19 (coronavirus disease 2019) evolves with clinical symptoms that vary widely in severity, from mild symptoms to critical conditions, which can even result in the patient's death. A critical aspect related to an individual response to SARS-CoV-2 infection is the competence of the immune system, and it is well known that several trace elements are essential for an adequate immune response and have anti-inflammatory and antioxidant properties that are of particular importance in fighting infection. Thus, it is widely accepted that adequate trace element status can reduce the risk of SARS-CoV-2 infection and disease severity. In this study, we evaluated the serum levels of Cu, Zn, Se, Fe, I and Mg in patients (n = 210) with clinical conditions of different severity ("mild", "moderate", "severe" and "exitus letalis", i.e., patients who eventually died). The results showed significant differences between the four groups for Cu, Zn, Se and Fe, in particular a significant trend of Zn and Se serum levels to be decreased and Cu to be increased with the severity of symptoms. For Mg and I, no differences were observed, but I levels were shown to be increased in all groups.