Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review.

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19.

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.

Could the Induction of Trained Immunity by ß-Glucan Serve as a Defense Against COVID-19?

As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. Throughout the literature, it has been shown that the induction of TRIM using such inducers as the BCG vaccine and ß-glucan can provide protection through altered immune responses against a range of viral infections. Here we hypothesize a potential role for ß-glucan in decreasing worldwide morbidity and mortality due to COVID-19, and posit several ideas as to how TRIM may actually shape the observed epidemiological phenomena related to COVID-19. We also evaluate the potential effects of ß-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral ß-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of ß-glucan's from various sources.

Immune-Boosting, Antioxidant and Anti-inflammatory Food Supplements Targeting Pathogenesis of COVID-19.

The COVID-19 is an acute and contagious disease characterized by pneumonia and ARDS. The disease is caused by SARS-CoV-2, which belongs to the family of Coronaviridae along with MERS-CoV and SARS-CoV-1. The virus has the positive-sense RNA as its genome encoding for ~26 proteins that work together for the virus survival, replication, and spread in the host. The virus gets transmitted through the contact of aerosol droplets from infected persons. The pathogenesis of COVID-19 is highly complex and involves suppression of host antiviral and innate immune response, induction of oxidative stress followed by hyper inflammation described as the "cytokine storm," causing the acute lung injury, tissue fibrosis, and pneumonia. Currently, several vaccines and drugs are being evaluated for their efficacy, safety, and for determination of doses for COVID-19 and this requires considerable time for their validation. Therefore, exploring the repurposing of natural compounds may provide alternatives against COVID-19. Several nutraceuticals have a proven ability of immune-boosting, antiviral, antioxidant, anti-inflammatory effects. These include Zn, vitamin D, vitamin C, curcumin, cinnamaldehyde, probiotics, selenium, lactoferrin, quercetin, etc. Grouping some of these phytonutrients in the right combination in the form of a food supplement may help to boost the immune system, prevent virus spread, preclude the disease progression to severe stage, and further suppress the hyper inflammation providing both prophylactic and therapeutic support against COVID-19.

Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection.

Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2.

Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors.

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kß (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

Prolonged QT Interval in a Patient With Coronavirus Disease-2019: Beyond Hydroxychloroquine and Azithromycin.

Recent reports have suggested an increased risk of QT prolongation and subsequent life-threatening ventricular arrhythmias, particularly torsade de pointes, in patients with coronavirus disease-2019 (COVID-19) treated with hydroxychloroquine and azithromycin. In this article, we report the case of a 75-year-old female with a baseline prolonged QT interval in whom the COVID-19 illness resulted in further remarkable QT prolongation (>700 ms), precipitating recurrent self-terminating episodes of torsade de pointes that necessitated temporary cardiac pacing. Despite the correction of hypoxemia and the absence of reversible factors, such as adverse medication effects, electrolyte derangements, and usage of hydroxychloroquine/azithromycin, the QT interval remained persistently prolonged compared with the baseline with subsequent degeneration into ventricular tachycardia and death. Thus, we highlight that COVID-19 illness itself can potentially lead to further prolongation of QT interval and unmask fatal ventricular arrhythmias in patients who have a prolonged QT and low repolarization reserve at baseline.

Role of Immune Dysregulation in Increased Mortality Among a Specific Subset of COVID-19 Patients and Immune-Enhancement Strategies for Combatting Through Nutritional Supplements.

Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.

Micronutrients as immunomodulatory tools for COVID-19 management.

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.

[Nutritional management of the critically ill inpatient with COVID-19. A narrative review]. / Manejo nutricional del paciente hospitalizado críticamente enfermo con COVID-19. Una revisión narrativa.

INTRODUCTION: The current COVID-19 pandemic mainly affects older people, those with obesity or other coexisting chronic diseases such as type-2 diabetes and high blood pressure. It has been observed that about 20 % of patients will require hospitalization, and some of them will need the support of invasive mechanical ventilation in intensive care units. Nutritional status appears to be a relevant factor influencing the clinical outcome of critically ill patients with COVID-19. Several international guidelines have provided recommendations to ensure energy and protein intake in people with COVID-19, with safety measures to reduce the risk of infection in healthcare personnel. The purpose of this review is to analyze the main recommendations related to adequate nutritional management for critically ill patients with COVID-19 in order to improve their prognosis and clinical outcomes.

INTRODUCCIÓN: La pandemia actual por COVID-19 afecta principalmente a personas mayores, con obesidad o con otras enfermedades crónicas coexistentes como diabetes de tipo 2 e hipertensión arterial. Se ha observado que alrededor del 20 % de los pacientes requerirán hospitalización y algunos de ellos necesitarán soporte de ventilación mecánica invasiva en unidades de cuidados intensivos. El estado nutricional parece ser un factor relevante que influye en el resultado clínico de los pacientes con COVID-19 críticamente enfermos. Diversas guías internacionales han publicado recomendaciones para asegurar la ingesta energética y proteica de las personas con COVID-19, junto con medidas de seguridad para disminuir el riesgo de infección por parte del personal de salud. El propósito de esta revisión es analizar las principales recomendaciones relacionadas con el adecuado manejo nutricional del paciente hospitalizado críticamente enfermo con COVID-19 con la finalidad de mejorar el pronóstico y los resultados clínicos.

Effects of Probiotics in Conditions or Infections Similar to COVID-19 on Health Outcomes: An Evidence Analysis Center Scoping Review.

Probiotics have been suggested as a potential intervention for improving outcomes, particularly ventilatory-associated pneumonia, in patients infected with coronavirus disease 2019 (COVID-19). However, with the rapid development of the COVID-19 pandemic, there is little direct evidence available in infected patients. The objective of this scoping review is to examine the availability and nature of literature describing the effect of probiotics in adults with conditions or infections similar to COVID-19 infection on related health outcomes. MEDLINE, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Databases were searched for studies published from 1999 to May 1, 2020, examining the effect of probiotics in conditions applicable to individuals infected with COVID-19, including, but not limited to, other forms of coronavirus, critical illness, and mechanical ventilation. The databases search identified 1925 unique articles, 77 full-text articles were reviewed, and 48 studies were included in this scoping review, including 31 primary studies and 17 systematic reviews. Primary studies examined a range of interventions that varied by probiotic diversity and types, including 8 studies that focused on synbiotics, which include both pre- and probiotics. Several systematic reviews examined the effect of probiotics on ventilator-associated pneumonia and other infections. Although most systematic reviews concluded probiotics may improve these outcomes, most systematic review authors concluded that the evidence was low in quality and high in heterogeneity. In the absence of direct evidence with patients infected with COVID-19, studies in comparable populations are currently the best resource to guide probiotics interventions in conjunction with clinical expertise and multidisciplinary health care planning.

Nutrition management for critically and acutely unwell hospitalised patients with coronavirus disease 2019 (COVID-19) in Australia and New Zealand.

Coronavirus disease 2019 (COVID-19) results from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features and subsequent medical treatment, combined with the impact of a global pandemic, require specific nutritional therapy in hospitalised adults. This document aims to provide Australian and New Zealand clinicians with guidance on managing critically and acutely unwell adult patients hospitalised with COVID-19. These recommendations were developed using expert consensus, incorporating the documented clinical signs and metabolic processes associated with COVID-19, the literature from other respiratory illnesses, in particular acute respiratory distress syndrome, and published guidelines for medical management of COVID-19 and general nutrition and intensive care. Patients hospitalised with COVID-19 are likely to have preexisting comorbidities, and the ensuing inflammatory response may result in increased metabolic demands, protein catabolism, and poor glycaemic control. Common medical interventions, including deep sedation, early mechanical ventilation, fluid restriction, and management in the prone position, may exacerbate gastrointestinal dysfunction and affect nutritional intake. Nutrition care should be tailored to pandemic capacity, with early gastric feeding commenced using an algorithm to provide nutrition for the first 5-7 days in lower-nutritional-risk patients and individualised care for high-nutritional-risk patients where capacity allows. Indirect calorimetry should be avoided owing to potential aerosole exposure and therefore infection risk to healthcare providers. Use of a volume-controlled, higher-protein enteral formula and gastric residual volume monitoring should be initiated. Careful monitoring, particularly after intensive care unit stay, is required to ensure appropriate nutrition delivery to prevent muscle deconditioning and aid recovery. The infectious nature of SARS-CoV-2 and the expected high volume of patient admissions will require contingency planning to optimise staffing resources including upskilling, ensure adequate nutrition supplies, facilitate remote consultations, and optimise food service management. These guidelines provide recommendations on how to manage the aforementioned aspects when providing nutrition support to patients during the SARS-CoV-2 pandemic.

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19.

Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

Safety issues and harmful pharmacological interactions of nutritional supplements in Duchenne muscular dystrophy: considerations for Standard of Care and emerging virus outbreaks.

At the moment, little treatment options are available for Duchenne muscular dystrophy (DMD). The absence of the dystrophin protein leads to a complex cascade of pathogenic events in myofibres, including chronic inflammation and oxidative stress as well as altered metabolism. The attention towards dietary supplements in DMD is rapidly increasing, with the aim to counteract pathology-related alteration in nutrient intake, the consequences of catabolic distress or to enhance the immunological response of patients as nowadays for the COVID-19 pandemic emergency. By definition, supplements do not exert therapeutic actions, although a great confusion may arise in daily life by the improper distinction between supplements and therapeutic compounds. For most supplements, little research has been done and little evidence is available concerning their effects in DMD as well as their preventing actions against infections. Often these are not prescribed by clinicians and patients/caregivers do not discuss the use with their clinical team. Then, little is known about the real extent of supplement use in DMD patients. It is mistakenly assumed that, since compounds are of natural origin, if a supplement is not effective, it will also do no harm. However, supplements can have serious side effects and also have harmful interactions, in terms of reducing efficacy or leading to toxicity, with other therapies. It is therefore pivotal to shed light on this unclear scenario for the sake of patients. This review discusses the supplements mostly used by DMD patients, focusing on their potential toxicity, due to a variety of mechanisms including pharmacodynamic or pharmacokinetic interactions and contaminations, as well as on reports of adverse events. This overview underlines the need for caution in uncontrolled use of dietary supplements in fragile populations such as DMD patients. A culture of appropriate use has to be implemented between clinicians and patients' groups.

Nutritional Support in Coronavirus 2019 Disease.

The epidemic that broke out in Chinese Wuhan at the beginning of 2020 presented how important the rapid diagnosis of malnutrition (elevating during intensive care unit stay) and the immediate implementation of caloric and protein-balanced nutrition care are. According to specialists from the Chinese Medical Association for Parenteral and Enteral Nutrition (CSPEN), these activities are crucial for both the therapy success and reduction of mortality rates. The Chinese have published their recommendations including principles for the diagnosis of nutritional status along with the optimal method for nutrition supply including guidelines when to introduce education approach, oral nutritional supplement, tube feeding, and parenteral nutrition. They also calculated energy demand and gave their opinion on proper monitoring and supplementation of immuno-nutrients, fluids and macronutrients intake. The present review summarizes Chinese observations and compares these with the latest European Society for Clinical Nutrition and Metabolism guidelines. Nutritional approach should be an inseparable element of therapy in patients with COVID-19.