bims-covind Biomed News
on COVID-19 and Immunology: nutrition and diet
Issue of 2020‒11‒29
twenty papers selected by
Aimee Cook
Newcastle University


  1. Virus Res. 2020 Nov 21. pii: S0168-1702(20)31142-4. [Epub ahead of print] 198235
    Kumar R, Himani , Haq A, Wimalawansa SJ, Sharma A.
      The first incidence of COVID-19 was reported in the Wuhan city of Hubei province in China in late December 2019. Because of failure in timely closing of borders of the affected region, COVID-19 spread across like a wildfire through air travel initiating a pandemic. It is a serious lower respiratory track viral infection caused by highly contagious, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Coronavirus including COVID-19 causing SARS-CoV-2 causes zoonotic diseases and thought to be originated from bats. Since its first incidence, the virus has spread all across the world, causing serious human casualties, economic losses, and disrupting global supply chains. As with SARS-CoV, COVID-19 causing SARS-CoV-2 follows a similar path of airborne infection, but is less lethal and more infectious than SARS and MERS. This review focusses on the pathogenesis of SARS-CoV-2, especially on the dysfunctional immune responses following a cytokine storm in severely affected persons. The mode of entry of SARS-CoV-2 is via the angiotensin converting enzyme 2 (ACE-2) receptors present on the epithelial lining of lungs, gastrointestinal tract, and mucus membranes. Older persons with weaker immune system and associated co-morbidities are more vulnerable to have dysfunctional immune responses, as most of them concomitantly have severe hypovitaminosis D. Consequently, causing severe damage to key organs of the body including lungs and the cardiovascular system. Since, vast majority of persons enters to the intensive care units and died, had severe vitamin D deficiency, thus, this area must be investigated seriously. In addition, this article assesses the role of vitamin D in reducing the risk of COVID-19. Vitamin D is a key regulator of the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Further, vitamin D modulates multiple mechanisms of the immune system to contain the virus that includes dampening the entry and replication of SARS-CoV-2, reduces concentration of pro-inflammatory cytokines and increases levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activates defensive cells such as macrophages that could destroy SARS-CoV-2. Thus, this article provides the urgency of needed evidences through large population based randomized controlled trials and ecological studies to evaluate the potential role of vitamin D in COVID-19.
    Keywords:  COVID-19; SARS-CoV-2; acute respiratory distress syndrome (ARDS); coronavirus; cytokine storm; dexamethasone; immune response; treatment; vitamin D
    DOI:  https://doi.org/10.1016/j.virusres.2020.198235
  2. Gastroenterol Hepatol Bed Bench. 2020 ;13(4): 331-340
    Bold J, Harris M, Fellows L, Chouchane M.
      The current review aimed to synthesize the literature on the complex relationship between food consumption and nutritional status as well as the digestive system in order to examine the relationship between immunity and potential responses to COVID-19 infection. The goal is to help inform the many healthcare professionals working with COVID-19 patients. A literature search was performed on PubMed, Scopus, and EMBASE databases. Hand searches were also undertaken using Google and reference lists to identify recent evidence. Studies were critically appraised, and the findings were analyzed by narrative synthesis. Nutritional status can impact immunity in several ways, including affecting susceptibility to infection, severity of disease, and recovery time, and is therefore a significant consideration in the management of COVID-19. COVID-19 can also impact digestive function, which can further impact nutritional status. The role of Vitamin D deficiency in vulnerability to severe respiratory infections, including COVID-19, has been recognized, and it may have a role in treatment where deficiency is indicated. Healthcare professionals should be aware that obesity may be accompanied by micronutrient malnutrition including vitamin D deficiency and alterations in the microbiome and inflammatory responses, which can further impact immunity and disease severity. Multidisciplinary team-work is recommended in the management of patients with COVID-19, and approaches should include a consideration of nutritional status (both macronutrients and micronutrients), body weight, and gastrointestinal signs and symptom.
    Keywords:  COVID-19; Microbiome; Multidisciplinary; Nutritional status; Obesity; Practice; Supplementation; Vitamin D
  3. BMJ Nutr Prev Health. 2020 ;3(1): 74-92
    Calder PC.
      The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B6, B12, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.
    Keywords:  infectious disease; malnutrition; microbiome; nutrient deficiencies; pulmonary disease
    DOI:  https://doi.org/10.1136/bmjnph-2020-000085
  4. BMJ Nutr Prev Health. 2020 ;3(1): 67-73
    Kohlmeier M.
      Vitamin D deficiency, which impedes good immune function, is common during winter and spring in regions of high latitude. There is good evidence that vitamin D deficiency contributes to the seasonal increase of virus infections of the respiratory tract, from the common cold to influenza, and now possibly also COVID-19. This communication explores key factors that make it more likely, particularly in combination, that individuals are vitamin D deficient. These factors include old age, obesity, dark skin tone and common genetic variants that impede vitamin D status. Precision nutrition is an approach that aims to consider known personal risk factors and health circumstances to provide more effective nutrition guidance in health and disease. In regard to avoiding vitamin D deficiency, people with excess body fat, a dark skin tone or older age usually need to use a moderately dosed daily vitamin D supplement, particularly those living in a high-latitude region, getting little ultraviolet B exposure due to air pollution or staying mostly indoors. Carriers of the GC (group-specific component) rs4588 AA genotype also are more likely to become deficient. Very high-dosed supplements with more than 4000 IU vitamin D are rarely needed or justified. A state-by-state Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the USA shows a greater disparity in northern states than in southern states. It is conceivable that vitamin D adequacy denies the virus easy footholds and thereby slows spreading of the contagion. This finding should drive home the message that vitamin D supplementation is particularly important for individuals with dark skin tones. Vitamin D deficiency, even for a few months during the winter and spring season, must be rigorously remedied because of its many adverse health impacts that include decreased life expectancy and increased mortality. Slowing the spread of COVID-19 would be an added bonus.
    Keywords:  dietary patterns; infectious disease; nutrient deficiencies; precision nutrition; pulmonary disease
    DOI:  https://doi.org/10.1136/bmjnph-2020-000096
  5. Am J Clin Pathol. 2020 Nov 25. pii: aqaa252. [Epub ahead of print]
    De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA.
      OBJECTIVES: Vitamin D deficiency was previously correlated with incidence and severity of coronavirus disease 2019 (COVID-19). We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) level on admission and radiologic stage and outcome of COVID-19 pneumonia.METHODS: A retrospective observational trial was done on 186 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals hospitalized from March 1, 2020, to April 7, 2020, with combined chest computed tomography (CT) and 25(OH)D measurement on admission. Multivariate regression analysis was performed to study if vitamin D deficiency (25(OH)D <20 ng/mL) correlates with survival independently of confounding comorbidities.
    RESULTS: Of the patients with COVID-19, 59% were vitamin D deficient on admission: 47% of females and 67% of males. In particular, male patients with COVID-19 showed progressively lower 25(OH)D with advancing radiologic stage, with deficiency rates increasing from 55% in stage 1 to 74% in stage 3. Vitamin D deficiency on admission was not confounded by age, ethnicity, chronic lung disease, coronary artery disease/hypertension, or diabetes and was associated with mortality (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.30-11.55), independent of age (OR, 1.09; 95% CI, 1.03-1.14), chronic lung disease (OR, 3.61; 95% CI, 1.18-11.09), and extent of lung damage expressed by chest CT severity score (OR, 1.12; 95% CI, 1.01-1.25).
    CONCLUSIONS: Low 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality.
    Keywords:  25(OH)D; COVID-19 disease; Coronavirus; Laboratory analysis; SARS-CoV-2; Viral pneumonia; Vitamin D deficiency
    DOI:  https://doi.org/10.1093/ajcp/aqaa252
  6. Foods. 2020 Nov 20. pii: E1701. [Epub ahead of print]9(11):
    Galanakis CM, Aldawoud TMS, Rizou M, Rowan NJ, Ibrahim SA.
      As media reports have noted, the COVID-19 pandemic has accelerated market mainstreaming of immune-boosting food bioactives, supplements, and nutraceuticals. However, most studies reporting on the potential of bioactives against COVID-19 transmission have been uploaded as preprints with little opportunity to revise content for benefit and impact. The current review discusses current best evidence and information underpinning the role of food ingredients and bioactive compounds in supporting immune functions in humans and animals, specifically in the prevention and treatment of COVID-19 disease. Up to now, some evidence from randomized population and clinical trials has suggested that vitamin D levels may be linked to COVID-19 transmission and severity. Numerous theoretical studies have pointed to polyphenols and particularly flavonoids as potential inhibitors of SARS-CoV-2 infection. There is also inconclusive evidence to support the future use of β-glucan to address COVID-19 due in part to variability in immune response arising from heterogeneity in polysaccharide branch and chain length for different sources and the absence of a standardized extraction method. To confirm the promising outcomes and hypotheses for bioactive compounds, more randomized and controlled clinical studies are needed. The results of such studies would have a profound effect on the prospects of food supplements and nutraceuticals as potential prophylaxis against COVID-19 and serve to help consumers to protect themselves during the post-lockdown recovery era.
    Keywords:  COVID-19; SARS-CoV-2; functional foods; immune system; nutraceuticals; vitamin D
    DOI:  https://doi.org/10.3390/foods9111701
  7. BMC Complement Med Ther. 2020 Nov 23. 20(1): 353
    Ng JY.
      BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2, and responsible for a global pandemic. Despite there being no known vaccines or medicines that prevent or cure COVID-19, many traditional, integrative, complementary and alternative medicines (TICAMs) have been touted as the solution, as well as researched as a potential remedy globally. This study presents a bibliometric analysis of global research trends at the intersection of TICAM and COVID-19.METHODS: SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020, with results being exported on the same day. All publication types were included, however, articles were only deemed eligible if they made mention of one or more TICAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned.
    RESULTS: A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included China, the United States, India and Italy. The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were TICAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 TICAMs were mentioned across eligible articles, with the most common ones including: traditional Chinese medicine (n = 94), vitamin D (n = 67), melatonin (n = 16), phytochemicals (n = 12), and general herbal medicine (n = 11).
    CONCLUSIONS: This study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and TICAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of TICAM therapies and COVID-19.
    Keywords:  Bibliometric analysis; COVID-19; Complementary and alternative medicine; Coronavirus; Herbal; Integrative medicine; Research trends; Traditional Chinese medicine; Traditional medicine
    DOI:  https://doi.org/10.1186/s12906-020-03151-8
  8. Biochim Biophys Acta Gen Subj. 2020 Nov 22. pii: S0304-4165(20)30312-3. [Epub ahead of print] 129801
    Celik C, Gencay A, Ocsoy I.
      BACKGROUND: Due to lack of approved drugs and vaccines, the medical world has resorted to older drugs, produced for viral infections and other diseases, as a remedy to combat COVID-19. The accumulating evidence from in vitro and in vivo studies for SARS-CoV and MERS-CoV have demonstrated that several polyphenols found in plants and zinc- polyphenol clusters have been in use as herbal medicines have antiviral activities against viruses with various mechanisms.SCOPE OF REVIEW: Curcumin, zinc and zinc-ionophores have been considered as nutraceuticals and nutrients showing great antiviral activities with their medicinal like activities.
    MAJOR CONCLUSIONS: In this work, we discussed the potential prophylactic and/or therapeutic effects of curcumin, zinc and zinc-ionophores in treatment of viral infections including COVID-19.
    GENERAL SIGNIFICANCE: Curcuminoids and Zinc classified as nutraceuticals under GRAS (Generally Recognized As Safe) by FDA can provide complementary treatment for COVID 19 patients with their immunity-boosting and antiviral properties.
    DOI:  https://doi.org/10.1016/j.bbagen.2020.129801
  9. Future Sci OA. 2020 Aug 18. 6(9): FSO628
    d'Arqom A, G Putri M, Savitri Y, Rahul Alfaidin AM.
      Aim: Low levels of immune-related micronutrients have been identified in β-thalassemia samples. Moreover, the excess amount of iron, contributing to oxidative stress in the pathogenesis of the disease, alters the immune system in β-thalassemia, which is important during the COVID-19 pandemic.Materials & Methods: Searches of PUBMED and EMBASE were conducted to identify the level and supplementation of micronutrients in β-thalassemia, published from 2001-May 2020.
    Results: The review found six observational and five interventional studies supporting the importance of supplementing vitamins and minerals among patients with β-thalassemia.
    Conclusion: Supplementation of immune-related vitamins and minerals might bring benefits to the immune system, especially in reducing oxidative stress in β-thalassemia.
    Keywords:  SARS-CoV-2; ascorbic acid; cholecalciferol; good health and well being; immunity; selenium; tocopherol; zinc
    DOI:  https://doi.org/10.2144/fsoa-2020-0110
  10. Aging (Albany NY). 2020 Nov 22. 12
    Wang B, Kovalchuk A, Li D, Rodriguez-Juarez R, Ilnytskyy Y, Kovalchuk I, Kovalchuk O.
      With the current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. The inhibition of viral entry and thus spread is a plausible therapeutic avenue. SARS-CoV-2 uses receptor-mediated entry into a human host via the angiotensin-converting enzyme 2 (ACE2), which is expressed in lung tissue as well as the oral and nasal mucosa, kidney, testes and gastrointestinal tract. The modulation of ACE2 levels in these gateway tissues may be an effective strategy for decreasing disease susceptibility. Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. However, its effects on ACE2 expression remain unknown. Working under a Health Canada research license, we developed over 800 new C. sativa cultivars and hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, we identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells. While our most effective extracts require further large-scale validation, our study is important for future analyses of the effects of medical cannabis on COVID-19. The extracts of our most successful novel high-CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.
    Keywords:  ACE2 receptor; CBD; COVID-19; SARS-CoV2; medical cannabis
    DOI:  https://doi.org/10.18632/aging.202225
  11. BMJ Nutr Prev Health. 2020 ;3(1): 100-105
    Derbyshire E, Delange J.
      In late December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei, China, resulting in the potentially fatal COVID-19. It went on to be officially recognised as a pandemic by the World Health Organisation on 11 March 2020. While many public health strategies have evolved, there has been little mention of the immune system and how this could be strengthened to help protect against viral infections such as SARS-CoV-2. The present paper evaluates the current evidence base relating to immunonutrition, with a particular focus on respiratory viruses. Within the nutrition sector a promising body of evidence studying inter-relationships between certain nutrients and immune competence already exists. This could potentially be an important player in helping the body to deal with the coronavirus, especially among elders. Evidence for vitamins C, D and zinc and their roles in preventing pneumonia and respiratory infections (vitamins C and D) and reinforcing immunity (zinc) appears to look particularly promising. Ongoing research within this important field is urgently needed.
    Keywords:  infectious disease; nutrient deficiencies; preventive counselling; pulmonary disease
    DOI:  https://doi.org/10.1136/bmjnph-2020-000071
  12. Int J Mol Med. 2020 Nov 18.
    Pormohammad A, Monych NK, Turner RJ.
      RNA‑dependent RNA‑polymerase (RdRp) and 3C‑like proteinase (3CLpro) are two main enzymes that play a key role in the replication of SARS‑CoV‑2. Zinc (Zn) has strong immunogenic properties and is known to bind to a number of proteins, modulating their activities. Zn also has a history of use in viral infection control. Thus, the present study models potential Zn binding to RdRp and the 3CLpro. Through molecular modeling, the Zn binding sites in the aforementioned two important enzymes of viral replication were found to be conserved between severe acute respiratory syndrome (SARS)‑coronavirus (CoV) and SARS‑CoV‑2. The location of these sites may influence the enzymatic activity of 3CLpro and RdRp in coronavirus disease 2019 (COVID‑19). Since Zn has established immune health benefits, is readily available, non‑expensive and a safe food supplement, with the comparisons presented here between SARS‑CoV and COVID‑19, the present study proposes that Zn could help ameliorate the disease process of COVID‑19 infection.
    DOI:  https://doi.org/10.3892/ijmm.2020.4790
  13. BMJ Nutr Prev Health. 2020 ;3(1): 111-117
    Mossink JP.
      The present spread of severe acute respiratory syndrome coronavirus 2, provoking COVID-19 disease, progresses rapidly worldwide. In current absence of a curative treatment and an effective, safe vaccine, there is a pressing need to focus on identifying and correcting deficits in immune function in order to reduce risk of severe progress of the disease and to lower the number of infections and fatalities. This paper evaluates the most recent literature on zinc status related to antiviral immunity and its possible role in COVID-19. It is concluded that zinc is a critical factor for antiviral immunity. There is ample evidence suggesting that zinc depletion, also prevalent in high-income nations, compromises immune functions. Notably, major risk groups for COVID-19, the elderly, men more than women, obese individuals and patients with diabetes are all at risk of zinc deficiency. Moreover, various widely used antihypertensive drugs and statin therapy have been reported to negatively influence zinc status. As zinc depletion impairs antiviral immunity, it is hypothesised to increase susceptibility for COVID-19. Therefore, dietary preventive measures and prompt implementation of zinc supplementation for risk groups should be considered. Large-scale studies are urgently needed to investigate the role of micronutrients and antiviral immunity, in particular drug-micronutrient immunity interaction.
    Keywords:  diabetes mellitus; dietary patterns; infectious disease; nutrient deficiencies; nutritional treatment
    DOI:  https://doi.org/10.1136/bmjnph-2020-000095
  14. Med Hypotheses. 2020 Nov 20. pii: S0306-9877(20)33294-1. [Epub ahead of print] 110403
    Ateya AM, Sabri NA.
      
    DOI:  https://doi.org/10.1016/j.mehy.2020.110403
  15. Biol Trace Elem Res. 2020 Nov 27.
    Abd-Elsalam S, Soliman S, Esmail ES, Khalaf M, Mostafa EF, Medhat MA, Ahmed OA, El Ghafar MSA, Alboraie M, Hassany SM.
      No specific treatment for COVID-19 infection is available up till now, and there is a great urge for effective treatment to reduce morbidity and mortality during this pandemic. We aimed to evaluate the effect of combining chloroquine/hydroxychloroquine (CQ/HCQ) and zinc in the treatment of COVID-19 patients. This was a randomized clinical trial conducted at three major University hospitals in Egypt. One hundred ninety-one patients with a confirmed diagnosis of COVID-19 infection were randomized into two groups: group I (96) patients received both HCQ and zinc, and group II (95) received HCQ only. The primary endpoints were the recovery within 28 days, the need for mechanical ventilation, and death. The two groups were matched for age and gender. They had no significant difference regarding any of the baseline laboratory parameters or clinical severity grading. Clinical recovery after 28 days was achieved by 79.2% in the zinc group and 77.9% in zinc-free treatment group, without any significant difference (p = 0.969). The need for mechanical ventilation and the overall mortality rates did not show any significant difference between the 2 groups either (p = 0.537 and 0.986, respectively). The age of the patient and the need for mechanical ventilation were the only risk factors associated with the patients' mortality by the univariate regression analysis (p = 0.001 and < 0.001, respectively). Zinc supplements did not enhance the clinical efficacy of HCQ. More randomized studies are needed to evaluate the value of adding zinc to other therapies for COVID 19. ClinicalTrials.gov Identifier: NCT04447534.
    Keywords:  Antioxidants; COVID 19; Chloroquine; Treatment; Zinc
    DOI:  https://doi.org/10.1007/s12011-020-02512-1