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COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation.
Zabetakis, I, Lordan, R, Norton, C, Tsoupras, A
Nutrients. 2020;12(5)
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By May 2020, the novel coronoavirus COVID-19 had infected over 4 million people worldwide. Spread through droplet, it gains entry to body cells through ACE2 cell receptors, causing viral infection-related inflammation, and predominantly infects the lower respiratory tract. Those with non-communicable diseases with COVID-19 experience increased inflammation and have a higher risk of adverse outcomes and mortality. This review article gives details of the mechanisms involved in a cytokine storm (an uncontrolled inflammatory response) and current treatment options, before discussing the immune-balancing and anti-inflammatory potential of healthy nutrition in reducing susceptibility to developing infections. Nutrition Practitioners looking to support the immunity and inflammation of their clients will find the summary research presented in relation to dietary strategies, different food groups and nutrients a useful basis for further study.
Abstract
The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted "stay in place" or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.
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Pilot trial of a group cognitive behavioural therapy program for comorbid depression and obesity.
Lores, T, Musker, M, Collins, K, Burke, A, Perry, SW, Wong, ML, Licinio, J
BMC psychology. 2020;8(1):34
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Depression and obesity are significant global health concerns. Depression can significantly impact physical health and reduced immune function. The aim of this study was to examine the potential benefits of a novel group psychological intervention program. The study is a preliminary quasi-experimental (single-arm) before-after pilot trial of a newly developed group-based psychological intervention program for people with depression and comorbid obesity. The program consisted of 10 two-hour group sessions held weekly. A total of 24 participants were recruited to the program across two pilot groups. Results indicate that there was a significant reduction in participants’ depression and anxiety scores by program-end. Some evidence also shows improvements in weight-related negative cognitions. Authors conclude that the group therapy program therefore has considerable potential to be effective in helping people enjoy better mental health and improve health outcomes.
Abstract
BACKGROUND Depression and obesity are significant global health concerns that commonly occur together. An integrated group cognitive behavioural therapy program was therefore developed to simultaneously address comorbid depression and obesity. METHODS Twenty-four participants (63% women, mean age 46 years) who screened positively for depression with a body mass index ≥25 were recruited from a self-referred general population sample. The group therapy program (10 two-hour weekly sessions) was examined in a single-arm, before-after pilot trial, conducted in a behavioural health clinic in Adelaide, Australia. Primary outcomes included survey and assessment-based analyses of depression, anxiety, body image, self-esteem, and weight (kg), assessed at four time-points: baseline, post-intervention, three-months and 12-months post program. Eighteen participants (75%) completed the program and all assessments. RESULTS Significant improvements in depression, anxiety, self-esteem and body shape concern scores, several quality of life domains, eating behaviours and total physical activity (among others) - but not weight - were observed over the course of the trial. CONCLUSIONS Results from this pilot trial suggest that combining interventions for depression and obesity may be useful. Further development of the program, particularly regarding the potential for physical health benefits, and a randomised controlled trial, are warranted. TRIAL REGISTRATION Trial registration: ANZCTR, ACTRN12617001079336, 13 July 2017. Retrospectively registered after date of the first consent (6 July 2017), but before the date of the first intervention session (20 July 2017).
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Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans?
Jain, SK, Parsanathan, R
Journal of the American College of Nutrition. 2020;39(8):694-699
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African Americans are more susceptible to vitamin D deficiency. In addition they have lower amounts of cellular glutathione (GSH), which is an antioxidant produced in the body from L-cysteine, capable of affecting genes involved in vitamin D production. Clinical trials have indicated a relationship between vitamin D deficiency and poorer outcomes in patients with COVID-19. This review paper looked at data in humans, animal models and at the cellular level and proposed that African Americans are susceptible to vitamin D deficiency due to increased skin pigmentation affecting its production. Reduced GSH was attributed to decreased dietary intake of L-cysteine, and lower levels of biological compounds, which are involved in the production of GSH. Research surrounding vitamin D’s role in immunity and lowering viral infection risk was reviewed and several routes were proposed, such as increasing anti-microbial action, decreasing inflammation, increasing anti-oxidants and blocking viruses entering cells. It was concluded that randomised control trials on vitamin D supplementation have been underwhelming. This disconnect with trials showing a relationship between low vitamin D levels and poor clinical outcomes is due to the fact that vitamin D was tested in isolation. More randomised control trials are needed to investigate co-supplementation with L-cysteine on outcomes of COVID-19 infection in African Americans. Clinicians could use this review to understand the relationship between vitamin D and L-cysteine and, in lieu of any randomised control trials, as a potential justification for co- supplementation of Vitamin D and L-cysteine in patients with vitamin D deficiency and COVID-19.
Abstract
Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.
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Could Vitamins Help in the Fight Against COVID-19?
Jovic, TH, Ali, SR, Ibrahim, N, Jessop, ZM, Tarassoli, SP, Dobbs, TD, Holford, P, Thornton, CA, Whitaker, IS
Nutrients. 2020;12(9)
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Immunonutrition is the role of nutrient supplementation in modulating the immune system. While there are limited approaches to the prevention and treatment of Covid-19, the aim of this review was to critically assess the current evidence to identify vitamins in the context of respiratory disease and extrapolate the evidence to evaluate the role of immunonutrition in Covid-19. Over 200 studies were included in this review to assess the physiological role, therapeutic application in respiratory disease and relevance to Covid-19 of each vitamin. Based on the existing literature, the authors conclude the there is a potential preventative and supportive role for vitamin supplementation in fighting Covid-19, specifically vitamin A, E and D.
Abstract
There are limited proven therapeutic options for the prevention and treatment of COVID-19. The role of vitamin and mineral supplementation or "immunonutrition" has previously been explored in a number of clinical trials in intensive care settings, and there are several hypotheses to support their routine use. The aim of this narrative review was to investigate whether vitamin supplementation is beneficial in COVID-19. A systematic search strategy with a narrative literature summary was designed, using the Medline, EMBASE, Cochrane Trials Register, WHO International Clinical Trial Registry, and Nexis media databases. The immune-mediating, antioxidant and antimicrobial roles of vitamins A to E were explored and their potential role in the fight against COVID-19 was evaluated. The major topics extracted for narrative synthesis were physiological and immunological roles of each vitamin, their role in respiratory infections, acute respiratory distress syndrome (ARDS), and COVID-19. Vitamins A to E highlighted potentially beneficial roles in the fight against COVID-19 via antioxidant effects, immunomodulation, enhancing natural barriers, and local paracrine signaling. Level 1 and 2 evidence supports the use of thiamine, vitamin C, and vitamin D in COVID-like respiratory diseases, ARDS, and sepsis. Although there are currently no published clinical trials due to the novelty of SARS-CoV-2 infection, there is pathophysiologic rationale for exploring the use of vitamins in this global pandemic, supported by early anecdotal reports from international groups. The final outcomes of ongoing trials of vitamin supplementation are awaited with interest.
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The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19.
Carr, AC, Rowe, S
Nutrients. 2020;12(11)
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There are many parallels between the clinical presentations of pneumonia and sepsis with the novel coronavirus disease (COVID-19). This has enabled researchers to draw on decades of research and apply it the current pandemic. The purpose of this paper is to evaluate the potential role of Vitamin C in the prevention and treatment of COVID-19 based on existing research. Examining the current literature, the authors found many therapeutic properties of vitamin C applicable to the clinical presentations of COVID-19. These include modulating the immune system, decreasing inflammation and lessening complications in the lungs. Emerging research indicates that administering vitamin C early during respiratory infection may prevent its progression to sepsis, thus reducing organ failure. Additionally, a recent observational study has found low vitamin C status in critically ill patients with COVID-19, and numerous randomized controlled trials (RCTs) are currently assessing intravenous vitamin C in patients with COVID-19. Based on the current research, the authors warrant administering vitamin C to patients with low vitamin C levels and severe respiratory infections while optimistically awaiting results from current RCTs.
Abstract
Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.
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Vitamin C: an essential "stress hormone" during sepsis.
Marik, PE
Journal of thoracic disease. 2020;12(Suppl 1):S84-S88
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Most mammals can synthesise vitamin C, except humans, other primates and guinea pigs, who lost this ability through a mutation. It is estimated that goats produce 2-4g of vitamin C per day, but significantly more when stressed. Vitamin C is thought to play an important role in our stress response. This short review articles discusses the importance of vitamin C during stress, in particular the stress of sepsis. The adrenal glands, our “stress organs”, contain very high levels of vitamin C which is released when the hypothalamus-pituitary-adrenal (HPA) axis (which deals with our response to stressors) is stimulated. In animals, there is an inverse relationship between vitamin C internal manufacture and cortisol release under stress: the less vitamin C an animal can produce, the more cortisol they release. A number of vitamin C’s biological actions including antioxidant, anti-inflammatory, immune function, synthesis of the stress hormones adrenaline and noradrenaline and wound healing, may play an important role during a stress response. During sepsis vitamin C gets used up at alarming rate. Sepsis is a complex disease and vitamin C’s biological actions can affect many of the underlying pathophysiological processes. Preclinical and clinical studies have shown a beneficial effect of vitamin C in patients with sepsis and synergistic effects are seen with thiamine (vitamin B1), corticosteroids and antibiotics.
Abstract
The stress response is a preserved evolutionary response that functions to enhance the survival of the species. In mammals, the stress response is characterized by activation of the HPA axis and sympathoadrenal system (SAS) as well as the increased synthesis and secretion of vitamin C. Cortisol, catecholamines, and vitamin C act synergistically to increase hemodynamic reserve, maintain immune function and protect the host against excessive oxidant injury. Humans (and anthropoid apes) have lost the ability to synthesize vitamin C and therefore have an impaired stress response. The inability to produce vitamin C has serious implications in septic humans. Treatment with vitamin C appears to restore the stress response and improve the survival of stressed humans.
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Immediate and long-term consequences of COVID-19 infections for the development of neurological disease.
Heneka, MT, Golenbock, D, Latz, E, Morgan, D, Brown, R
Alzheimer's research & therapy. 2020;12(1):69
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Covid-19 may cause brain dysfunction evidenced by symptoms individuals experience once they have contracted the disease. Loss of smell, taste and confusion have all been reported by patients and a number of severe cases have reported incidences of stroke. These are all of concern, as Covid-19 can severely affect the elderly who ordinarily are the most likely to suffer from brain disorders. This small review paper of 27 studies stated that there are four possible ways in which Covid-19 may affect the brain, which put Covid-19 sufferers at an increased risk of long-term brain disorders. This was supported by findings, which showed one third of Covid-19 patients leave hospital with evidence of brain dysfunction. Inflammation was heavily reviewed by the authors as a possible causal factor. It was concluded that patients who survive Covid-19 infection are at an increased risk for developing brain disorders such as Alzheimer's disease, however it was acknowledged that further studies are required. Clinicians could use this study to understand the possible need for both short-term and long-term monitoring of brain function in individuals who have survived Covid-19, especially if they are elderly.
Abstract
Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.
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COVID-19 and diabetes: The why, the what and the how.
Cuschieri, S, Grech, S
Journal of diabetes and its complications. 2020;34(9):107637
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Early reports have shown that individuals with diabetes who contract Covid-19 have higher hospital admissions and mortality rates, classing them as a vulnerable group. This review paper aimed to explain why this group of people are vulnerable and what measures could be recommended. The paper outlined that individuals with diabetes have a compromised immune system due to uncontrolled blood sugar levels. In addition to this, individuals with diabetes and Covid-19 may have a higher risk of organ damage due to the effects of the body's immune response combined with the disordered biological processes associated with their pre-existing condition. Conversely, it was discussed that Covid-19 could exacerbate diabetes progression if the Covid-19 virus entered the cells of the pancreas, causing a blood sugar imbalance. As a result, the importance of optimal blood sugar control was outlined. Several medications were addressed and their benefits/disadvantages discussed. Amongst those reviewed were medications such as GLP-1 agonists, which may help with controlling blood sugar levels and may prevent Covid-19 entering the body's own cells, and metformin, which was initially developed as an anti-influenza drug. Finally the paper discussed diabetes specific precautions to avoid contracting Covid-19. Vitamin D supplementation, regular blood sugar checks, lifestyle measures such as exercise and dietary requirements and allowing individuals with diabetes to have large supplies of their medications to avoid leaving the house were discussed. It was concluded that during the Covid-19 pandemic, individuals with diabetes require particular care in order to avoid additional burden on healthcare systems. For those individuals with diabetes who haven’t contracted Covid-19, this paper could be used to recommend any extra precautions to take to avoid contracting this virus.
Abstract
BACKGROUND The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS A search using keywords "COVID-19" and "Diabetes" was performed using different sources, including PubMed and World Health Organization. RESULTS COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.
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Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.
Leung, TYM, Chan, AYL, Chan, EW, Chan, VKY, Chui, CSL, Cowling, BJ, Gao, L, Ge, MQ, Hung, IFN, Ip, MSM, et al
Emerging microbes & infections. 2020;9(1):2190-2199
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The Coronavirus pandemic (Covid-19) has infected millions of people worldwide and there is evidence that it affects many systems in the human body. This rapid review summarises the current evidence on short-term negative health outcomes of Covid-19. It also assesses the risk of potential long-term negative effects by looking at data from the other coronaviruses; Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The burden for caring for Covid-19 survivors is likely to be huge and so policy makers need suitable data to put the appropriate care strategies in place. The review is divided into sections as per body system affected: Immune, respiratory, cardiovascular, gastrointestinal, hepatic and renal, neurological, dermatological, mental health, pregnancy and prenatal exposure. The evidence (short-term and long-term) is then reviewed by experts in those fields. Further large-scale studies are needed to monitor the adverse effects and to measure the long-term health consequences.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
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Antiviral Functional Foods and Exercise Lifestyle Prevention of Coronavirus.
Alkhatib, A
Nutrients. 2020;12(9)
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In lieu of a vaccine, complementary therapies have a major role to play in the Covid-19 pandemic. This review paper aimed to highlight how lifestyle approaches such as consumption of functional foods and increased physical activity could optimise the immune system in response to viral infections such as respiratory tract infections and Covid-19, and act as a possible adjuvant to vaccination. The paper outlined the role of exercise as being controversial. Although exercise has been shown to activate white blood cells, intense exercise in elite athletes has been linked to higher upper respiratory tract infection rates. It appears that varying intensity and type of exercise may optimise the immune system and have an additive effect to immunisation against viruses like influenza. The authors also stated that having a sedentary lifestyle may impair the immune system and diseases such as obesity and diabetes may increase susceptibility to infections such as Covid-19. The antiviral effect of functional foods was discussed. The paper paid particular attention to olive oil, vitamin D, traditional herbs and roots, coffee and caffeine. The reviewed mechanisms included enhanced gut bacteria profiles and promotion of anti-oxidants and anti-inflammatories. The authors also stated that supplementation as well as adequate dietary intake might be of importance against Covid-19, especially in deficient individuals. It was concluded that moderate intensity exercise alongside dietary intake of functional foods, may prevent communicable diseases, such as Covid-19. Clinicians could use this paper to recommend specific functional foods plus moderate exercise, to help prevent viral infections like Covid-19.
Abstract
Novel coronavirus (COVID-19) is causing global mortality and lockdown burdens. A compromised immune system is a known risk factor for all viral influenza infections. Functional foods optimize the immune system capacity to prevent and control pathogenic viral infections, while physical activity augments such protective benefits. Exercise enhances innate and adaptive immune systems through acute, transient, and long-term adaptations to physical activity in a dose-response relationship. Functional foods prevention of non-communicable disease can be translated into protecting against respiratory viral infections and COVID-19. Functional foods and nutraceuticals within popular diets contain immune-boosting nutraceuticals, polyphenols, terpenoids, flavonoids, alkaloids, sterols, pigments, unsaturated fatty-acids, micronutrient vitamins and minerals, including vitamin A, B6, B12, C, D, E, and folate, and trace elements, including zinc, iron, selenium, magnesium, and copper. Foods with antiviral properties include fruits, vegetables, fermented foods and probiotics, olive oil, fish, nuts and seeds, herbs, roots, fungi, amino acids, peptides, and cyclotides. Regular moderate exercise may contribute to reduce viral risk and enhance sleep quality during quarantine, in combination with appropriate dietary habits and functional foods. Lifestyle and appropriate nutrition with functional compounds may offer further antiviral approaches for public health.