bims-covind Biomed News
on COVID-19 and Immunology: nutrition and diet
Issue of 2021–01–17
twenty papers selected by
Aimee Cook, Newcastle University



  1. Risk Manag Healthc Policy. 2021 ;14 31-38
       Introduction: Vitamin D status is related to risks of influenza and respiratory tract infections. Vitamin D has direct antiviral effects primarily against enveloped viruses, and coronavirus is an enveloped virus. The 2019 coronavirus disease had a high mortality rate and impacted the whole population of the planet, with severe acute respiratory syndrome the principal cause of death. Vitamin D can adequately modulate and regulate the immune and oxidative response to infection with COVID-19. The goal of this systematic review was thus to summarize and decide if there were a link between vitamin D status and COVID-19 infection and prognosis.
    Methods: The protocol of this study is documented in the Prospero database and can be accessed with the protocol number CRD42020201283. PubMed and Google Scholar were used for a literature search from August 2020 to September 2020. We restricted the year of publication of reviewed articles to 2019-2020, and the selected language was English. Studies that used secondary data, feedback, or analysis of reviews were removed. To assess the standard of studies included, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used.
    Results: Of the nine studies reviewed, seven (77.8%) showed that COVID-19 infection, prognosis, and mortality were correlated with vitamin D status.
    Conclusion: Most of the articles reviewed showed that blood vitamin D status can determine the risk of being infected with COVID-19, seriousness of COVID-19, and mortality from COVID-19. Therefore, maintaining appropriate levels of Vitamin D through supplementation or natural methods, eg, sunlight on the skin, is recommended for the public to be able to cope with the pandemic.
    Keywords:  COVID-19; infection; mortality; prognosis; vitamin D
    DOI:  https://doi.org/10.2147/RMHP.S291584
  2. Cas Lek Cesk. 2020 ;159(7-8): 312-316
      Vitamin D supplementation reduced the risk of acute respiratory tract infection in two meta-analyses. Mendelian randomization shows a causal effect of low vitamin D on bacterial pneumonias risk. These studies involved patients before COVID-19 pandemic. Several association studies found higher incidence of SARS-CoV-2 positivity, greater COVID-19 severity and higher risk of mortality in vitamin D deficient subjects compared to vitamin D non-deficient controls. We draw attention to the trend of inverse relative COVID-19 mortality in Europe versus the states of the Southern Hemisphere (Australia, Brazil, South Africa) in dependence on season, which may be associated with intensity of ultraviolet radiation and consequent seasonal fluctuation of serum vitamin D levels. Although we cannot yet confirm causal role of vitamin D in SARS-CoV-2 positivity or COVID-19, we recommend consumption of vitamin D rich food or vitamin D supplementation in the non-sunny season to prevent vitamin D deficiency.
    Keywords:  COVID-19; SARS-CoV-2; Vitamin D; vitamin
  3. Int J Vitam Nutr Res. 2021 Jan 13. 1-18
       The novel coronavirus (SARS-CoV-2) causing COVID-19 disease pandemic has infected millions of people and caused more than thousands of deaths in many countries across the world. The number of infected cases is increasing day by day. Unfortunately, we do not have a vaccine and specific treatment for it. Along with the protective measures, respiratory and/or circulatory supports and some antiviral and retroviral drugs have been used against SARS-CoV-2, but there are no more extensive studies proving their efficacy. In this study, the latest publications in the field have been reviewed, focusing on the modulatory effects on the immunity of some natural antiviral dietary supplements, vitamins and minerals. Findings suggest that several dietary supplements, including black seeds, garlic, ginger, cranberry, orange, omega-3 and -6 polyunsaturated fatty acids, vitamins (e.g., A, B vitamins, C, D, E), and minerals (e.g., Cu, Fe, Mg, Mn, Na, Se, Zn) have anti-viral effects. Many of them act against various species of respiratory viruses, including severe acute respiratory syndrome-related coronaviruses. Therefore, dietary supplements, including vitamins and minerals, probiotics as well as individual nutritional behaviour can be used as adjuvant therapy together with antiviral medicines in the management of COVID-19 disease.
    Keywords:  coronavirus; dietary supplements; immune system; micronutrients; minerals; pandemic COVID-19; respiratory viruses; vitamins
    DOI:  https://doi.org/10.1024/0300-9831/a000694
  4. Adv Nutr. 2021 Jan 13. pii: nmaa171. [Epub ahead of print]
      The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.
    Keywords:  Atlantic diet; COVID-19; Mediterranean diet; antioxidants; balanced diet; viral infections
    DOI:  https://doi.org/10.1093/advances/nmaa171
  5. J Am Coll Nutr. 2021 Jan 12. 1-11
       BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality.
    MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve.
    RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively.
    CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.
    Keywords:  COVID-19; hypocalcemia; in-hospital mortality; vitamin D deficiency
    DOI:  https://doi.org/10.1080/07315724.2020.1856013
  6. Int J Mol Med. 2021 Mar;pii: 11. [Epub ahead of print]47(3):
      Coronavirus disease 2019 (COVID‑19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS‑CoV‑2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non‑muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID‑19 in a case report that described the rapid recovery of a 78‑year‑old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID‑19.
    DOI:  https://doi.org/10.3892/ijmm.2021.4844
  7. FEBS J. 2020 Sep;287(17): 3689-3692
      The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the potential role of vitamin D supplementation to prevent COVID-19. In this issue, Merzon and colleagues report epidemiologic data on the vitamin D status of 7807 individuals and their risk of developing COVID-19. In multivariable analyses, low vitamin D status was associated with increased risk of both COVID-19 infection and hospitalization. The authors call for clinical trials of vitamin D supplementation. In this Commentary, we discuss some of the challenges of vitamin D research and provide recommendations for the design of randomized controlled trials of vitamin D supplementation to prevent COVID-19.
    Keywords:  COVID‐19; clinical trial; randomized controlled trial; vitamin D
    DOI:  https://doi.org/10.1111/febs.15534
  8. Trends Food Sci Technol. 2021 Feb;108 223-235
       Background: The global crisis caused by the outbreak of severe acute respiratory syndrome caused by the SARS-CoV-2 virus, better known as COVID-19, brought the need to improve the population's immunity. The foods rich in polysaccharides with immunomodulation properties are among the most highly rated to be used as immune response modulators. Thus, the use of polysaccharides obtained from food offers an innovative strategy to prevent serious side effects of viral infections.
    Scope and approach: This review revisits the current studies on the pathophysiology of SARS-CoV-2, its characteristics, target cell interactions, and the possibility of using polysaccharides from functional foods as activators of the immune response. Several natural foods are explored for the possibility of being used to obtain polysaccharides with immunomodulatory potential. And finally, we address expectations for the use of polysaccharides in the development of potential therapies and vaccines.
    Key findings and conclusions: The negative consequences of the SARS-CoV-2 pandemic across the world are unprecedented, thousands of lives lost, increasing inequalities, and incalculable economic losses. On the other hand, great scientific advances have been made regarding the understanding of the disease and forms of treatment. Polysaccharides, due to their characteristics, have the potential to be used as potential drugs with the ability to modulate the immune response. In addition, they can be used safely, as they have no toxic effects, are biocompatible and biodegradable. Finally, these biopolymers can still be used in the development of new therapies and vaccines.
    Keywords:  COVID-19; Functional foods; Immunomodulation; Polysaccharides; Vaccines
    DOI:  https://doi.org/10.1016/j.tifs.2020.12.026
  9. Postgrad Med J. 2021 Jan 15. pii: postgradmedj-2020-139388. [Epub ahead of print]
      
    Keywords:  COVID-19; epidemiology
    DOI:  https://doi.org/10.1136/postgradmedj-2020-139388
  10. J Biol Regul Homeost Agents. 2020 Nov-Dec;34(6 Suppl. 1):34(6 Suppl. 1): 41-49
      In the pandemic coronavirus disease 2019 (COVID-19) era, the need to use preventive-curative treatments is compelling. A series of non-pharmacological compounds, including supplements (oligoelements and vitamins), probiotics, and nutraceuticals, might affect the risk of COVID-19 or reducing clinical severity. Non-pharmacological remedies are easily available and usually have no relevant side effects. There is evidence that bacterial and molecular substances may potentiate the immune system against respiratory viruses. Moreover, these compounds might exert essential anti-inflammatory and antioxidant activity in COVID-19. Furthermore, nasal lavage may be an additional resource for reducing the viral load and restore the integrity of respiratory patency. Therefore, preventive courses using non-pharmacological remedies could be prescribed to reinforce the immune response and adequate treatment of upper respiratory infection with natural compounds could be considered a reasonable way to manage people in the pandemic COVID-19 era.
    Keywords:  COVID-19; microbiota, probiotics; nutraceuticals; oligo-elements; upper respiratory infections
  11. Gut. 2021 Jan 11. pii: gutjnl-2020-323020. [Epub ahead of print]
       OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
    METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.
    RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
    CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
    Keywords:  colonic bacteria; colonic microflora; inflammation
    DOI:  https://doi.org/10.1136/gutjnl-2020-323020
  12. Lancet Diabetes Endocrinol. 2021 Jan 08. pii: S2213-8587(21)00003-6. [Epub ahead of print]
      
    DOI:  https://doi.org/10.1016/S2213-8587(21)00003-6
  13. Nutrition. 2020 Dec 04. pii: S0899-9007(20)30386-5. [Epub ahead of print]84 111103
       OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic is seriously threatening public health and setting off huge economic crises across the world. In the absence of specific drugs for COVID-19, there is an urgent need to look for alternative approaches. Therefore, the aim of this paper was to review the roles of micronutrients and bioactive substances as potential alternative approaches in combating COVID-19.
    METHODS: This review was based on the literature identified using electronic searches in different databases.
    RESULTS: Vitamins (A, B, C, D, and E), minerals (selenium and zinc), and bioactive substances from curcumin, echinacea, propolis, garlic, soybean, green tea, and other polyphenols were identified as having potential roles in interfering with spike glycoproteins, angiotensin converting enzyme 2, and transmembrane protease serine 2 at the entry site, and inhibiting activities of papain-like protease, 3 chymotrypsin-like protease, and RNA-dependent RNA polymerase in the replication cycle of severe acute respiratory syndrome coronavirus 2. Having immunomodulating, antiinflammatory, antioxidant, and antiviral properties, such micronutrients and bioactive substances are consequently promising alterative nutritional approaches to combat COVID-19.
    CONCLUSIONS: The roles of micronutrients and bioactive substances in the fight against COVID-19 are exciting areas of research. This review may suggest directions for further study.
    Keywords:  Bioactive substances; COVID-19; Cytokine storms; Lung injury; Micronutrients; SARS-CoV-2
    DOI:  https://doi.org/10.1016/j.nut.2020.111103
  14. Saudi J Biol Sci. 2021 Jan;28(1): 865-869
      The beneficial live microbes of humans and animals are termed probiotics, and the chemical compounds that improve the growth of probiotics are known as prebiotics. Paraprobiotics and postbiotics refer to dead or inactivated living cells of probiotics and healthful metabolic products that are produced by the living cells of probiotics, respectively. Although the healthful, functional, nutritional, and immune benefits of probiotics and prebiotics are scientifically well established beyond a reasonable doubt, their potential biological roles against COVID-19 infection still warrant further clinical and laboratory investigation.
    Keywords:  COVID-19; FAO, Food and Agriculture Organization; Paraprobiotics; Postbiotics; Prebiotics; Probiotics; SARS-CoV-2; WHO, World Health Organization
    DOI:  https://doi.org/10.1016/j.sjbs.2020.11.025
  15. Indian J Microbiol. 2021 Jan 03. 1-4
      COVID-19 continues to be an ongoing global threat. The elderly with underlying health conditions like cardiovascular and lung diseases, diabetes, obesity, are the most vulnerable to this disease. Curing the pre-existing health conditions will greatly increase a person's resilience to COVID-19 and lower the death rate of the old people. Digestion and immunity form an integrated nutrition acquisition process, especially in obtaining essential amino acids and essential fatty acids from living microbial cells. A mature strong immunity coupled with gut dysbiosis in adults is the main cause of nutritional disorders like morbid obesity, diabetes mellitus, cardiovascular and pulmonary diseases. Nutrition disorders in return worsen dysbiosis. Human microbiome has an intrinsic duality. While a diverse microbiome provides a full spectrum of essential nutrients to our body, nutrition disorders fuel overgrowth of microbiota (dysbiosis) at many sites on or inside our body, and are the main causes of chronic inflammation at these sites. In the case of COVID-19, nutritional disorder impairs the immunity, causes hyperinflammation, and leads to the protracted overload of cytokines by the immune system, i.e., the cytokine storm. Autophagy induced by restrictive eating is an ideal inhibitor of microbiota overgrowth, as autophagy deprives microbiota of excessive nutrition for replication. Autophagy also attenuates inflammation. Therefore, as a precaution, the author suggests restoring good health in the elderly with the support from a diverse gut microbiome and daily regular food intake restriction, so as to lower the risk of developing into severe case even if they are infected by COVID-19.
    Keywords:  COVID-19; Digestive immunity; Gut microbiome; Metabolic syndromes; Restrictive eating
    DOI:  https://doi.org/10.1007/s12088-020-00913-3
  16. Med Hypotheses. 2021 Jan 04. pii: S0306-9877(20)33371-5. [Epub ahead of print]147 110480
      The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus is now considered a global public health threat. The primary focus has been on reducing the viral spread and treating respiratory symptoms; as time goes on, the impact of COVID-19 on neurological and haemostatic systems becomes more evident. The clinical data suggest that platelet hyperactivity plays a role in the pathology of COVID-19 from its onset and that platelets may serve critical functions during COVID-19 progression. Hyperactivation of blood platelets and the coagulation system are emerging as important drivers of inflammation and may be linked to the severity of the 'cytokine storm' induced in severe cases of COVID-19, in which disseminated intravascular coagulation, and platelet hyperactivity are associated with poor prognosis and increased risk of mortality. We propose that targeting platelet hyperactivity in the early stages of COVID-19 infection may reduce the immunothrombotic complications of COVID-19 and subdue the systemic inflammatory response. Lowering baseline platelet activity may be of particular importance for higher-risk groups. As an alternative to antiplatelet drugs, an inappropriate intervention in public health, we propose that the dietary antiplatelet agent Fruitflow®, derived from tomatoes, may be considered a suitable therapy. Fruitflow® contains antiplatelet and anti-inflammatory compounds that target the mechanisms of platelet activation specific to COVID-19 and can be considered a safe and natural antiplatelet regime.
    Keywords:  Blood pressure; COVID-19; Coagulation; Fruitflow®; Human platelets; Immunothrombosis; Inflammation; Platelet activation; Platelet hyperactivity; SARS-Cov-2 virus; Water-soluble tomato extract
    DOI:  https://doi.org/10.1016/j.mehy.2020.110480
  17. mBio. 2021 01 12. pii: e03022-20. [Epub ahead of print]12(1):
      Coronavirus disease 2019 (COVID-19), which has been declared a pandemic, has exhibited a wide range of severity worldwide. Although this global variation is largely affected by socio-medical situations in each country, there is also high individual-level variation attributable to elderliness and certain underlying medical conditions, including high blood pressure, diabetes, and obesity. As both elderliness and the aforementioned chronic conditions are often associated with an altered gut microbiota, resulting in disrupted gut barrier integrity, and gut symptoms have consistently been associated with more severe illness in COVID-19 patients, it is possible that dysfunction of the gut as a whole influences COVID-19 severity. This article summarizes the accumulating evidence that supports the hypothesis that an altered gut microbiota and its associated leaky gut may contribute to the onset of gastrointestinal symptoms and occasionally to additional multiorgan complications that may lead to severe illness by allowing leakage of the causative coronavirus into the circulatory system.
    Keywords:  COVID-19; SARS-CoV-2; coronavirus; gut barrier integrity; gut microbiota; leaky gut
    DOI:  https://doi.org/10.1128/mBio.03022-20
  18. New Microbes New Infect. 2021 Jan 06. 100837
      Defined as helpful live bacteria that can provide medical advantages to the host when administered in tolerable amounts, oral probiotics might be worth considering as a possible preventive or therapeutic modality to mitigate Coronavirus disease 2019 (COVID-19) symptom severity. This hypothesis stems from an emerging understanding of the gut-lung axis wherein probiotic microbial species in the digestive tract can influence systemic immunity, lung immunity, and possibly viral pathogenesis and secondary infection co-morbidities. We review the principles underlying the gut-lung axis, examples of probiotic-associated antiviral activities, and current clinical trials in COVID-19 based on oral probiotics.
    Keywords:  COVID-19; Probiotic; SARS-CoV-2; gut microbiome; gut-lung axis; secondary infection
    DOI:  https://doi.org/10.1016/j.nmni.2021.100837
  19. Explore (NY). 2020 Dec 26. pii: S1550-8307(20)30421-3. [Epub ahead of print]
      
    DOI:  https://doi.org/10.1016/j.explore.2020.12.009