Nutrition, the digestive system and immunity in COVID-19 infection
Gastroenterology and Hepatology from Bed to Bench,
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: obesity, COVID-19, nutritional status, vitamin D, microbiome, multidisciplinary, supplementation, practice.
(Please cite as: Bold J, Harris M, Fellows L, Chouchane M. Nutrition, the digestive system and immunity in COVID-19 infection. Gastroenterol Hepatol Bed Bench 2020;13(4):331-340).
- obesity, COVID-19, nutritional status, vitamin D, microbiome, multidisciplinary, supplementation, practice.
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Naja F, & Hamadeh R. Nutrition amid the COVID-19 pandemic: a multi-level framework for action. Eur J Clin Nutr 2020; 1–5. Advance online publication. https://doi.org/10.1038/s41430-020-0634-3
Castleden M, McKee M, Murray V, Leonardi G. Resilience thinking in health protection, J Public Health 2011; 33:3:369–377
British Dietetic Association (BDA). Malnutrition Food Fact sheet 2019. Available at https://www.bda.uk.com/uploads/assets/a3b7670b-7f77-4a9f-b5bf14179882b6d1/Malnutrition-food-fact-sheet.pdf 4. Frank M, Sivagnanaratnam A, Bernstein J Nutritional assessment in elderly care: a MUST! BMJ Open Qual 2015; 4:u204810.w2031. doi:10.1136/bmjquality.u204810.w2031
GBD Diet Collaborators Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019; 393: 1958-1972
Alwarawrah Y, Kiernan K, MacIver NJ. Changes in nutritional status impact immune cell metabolism and function. Front Immunol 2018; 9:1055. https://doi: 10.3389/fimmu.2018.01055
Gombar AF, Pierre A, Maggini S. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients 2020; 12:236. https://doi: 10.3390/nu12010236
Gleeson M, Nieman DC, Pedersen BK. Exercise, nutrition and immune function. J Sports Sci 2004; 22:115–25.
Valdés-Ramos R, Martínez-Carrillo BE, Aranda-González II, Gua- darrama AL, Pardo-Morales RV, Tlatempa P, et al. Diet, exercise and gut mucosal immunity. Proc Nutr Soc 2010; 69:644–50.
Wypych TP, Marsland BJ, Ubags ND. The impact of diet on immunity and respiratory diseases. Ann Am Thorac Soc 2017; 14: S339–47.
Grant WB, Lahore H, McDonnell SL, et al. (2020) Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020; 12:988. doi:10.3390/nu12040988
Zhou YF, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies. Medicine (Baltimore) 2019; 98:e17252. doi:10.1097/MD.0000000000017252
Frigstad SO, Høivik ML, Jahnsen J, et al. Pain Severity and Vitamin D Deficiency in IBD Patients. Nutrients 2019; 12:26. doi:10.3390/nu12010026
Alipio, M. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) 2020. Available at SSRN 3571484.
Richard A, Rohrmann S, & Quack Lötscher KC. Prevalence of Vitamin D Deficiency and Its Associations with Skin Color in Pregnant Women in the First Trimester in a Sample from Switzerland. Nutrients 2017; 9(3), 260. https://doi.org/10.3390/nu9030260
Kamlesh K, Kumar SA, Manish P, Wasim H. Is ethnicity linked to incidence or outcomes of covid-19? BMJ 2020; 369:m1548
Via M. The Malnutrition of Obesity: Micronutrient Deficiencies That Promote Diabetes. ISRN Endocrinol Volume 2012, Article ID 103472
Nair R, Maseeh A. Vitamin D: The "sunshine" vitamin. J Pharmacol Pharmacother. 2012; 3:118-26
British Nutrition Foundation (BNF) NDNS: time trend and income analyses for Years 1 to 9. 2019.
Patel JJ, Rosenthal MD, Miller KR, Martindale RG. The gut in trauma.Curr Opin Crit Care 2016; 22:339-346. doi:10.1097/MCC.0000000000000331
Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelinger C, Verschueren S, Houben E, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014; 63: 1293-1299. https://doi.org/10.1136/gutjnl-2013-305690.
Anderson G. Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondria functioning: pathoaetiological and pathophysiological implications. Melatonin Research 2019; 2:70-85. https://doi.org/10.32794/ mr11250022.
Al-Assal K, Martinez A, Torrinhas R, Cardinelli, Waitzberg D. Gut Microbiota and Obesity. Clin Nutr Exp 20 2018; 60-64. https://doi.org/10.1016/j.yclnex.2018.03.001
Tseng AH, & Wu CY. The Gut Microbiome in Obesity. J Formos Med Assoc 2019; 118:S3-S9. 52 https://doi.org/10.1016/j.jfma.2018.07.009
Anderson G, & Reiter RJ. Melatonin: Roles in influenza, COVID-19 and other viral infections. Rev Med Virol. 2020 e2109. https://doi.org/10.1002/rmv.2109
Bermudez-Brito M, Plaza-Diaz J, Munoz-Quezada S, Gomez-Llorente C, Gil A. Probiotic Mechanisms of Action. Ann Nutr Metab. 2012; 61:160-174.
Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by Short Chain Fatty Acids. Nutrients 2011; 3:858-876.
Schlee M, Harder J, Koten B, Stange EF, Wehkamp J, Fellermann K. Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol 2008; 151:528-535.
Lescheid DW. Probiotics as regulators of inflammation: A review. Funct Foods Health Dis. 2014; 4: 299–311.
Thomas CM, Versalovic J. Probiotics-host communication. Modulation of signaling pathways in the intestine. Gut Microbes 2010; 1:148-163.
Schroder K, Tschopp J. The inflammasomes Cell 2010; 140:821-832.
Doré J, Simrén M, Buttle L, Guarner F. Hot topics in gut microbiota. United European Gastroenterology Journal 2013; 1: 311-318.
Coombes JL, Powrie F. Dendritic cells in intestinal immune regulation. Nat Rev Immunol. 2008; 8: 435-46.
Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020; 285:198018.
Zhang H, Kang Z, Gong H, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv 2020. https://doi.org/10.1101/2020.01.30.927806
Jin X, Lian J-S, Hu J-H, Gao J, Zheng Y, Hao S, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020. http://dx.doi.org/10.1136/gutjnl-2020-320926
Tian Y, Rong L, Nian W, Yan H. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51:843-851.
Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J. et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am J Gastroenterol. 2020; 20.
Suárez-Fariñas M, Tokuyama M, Wei G, Huang R, Livanos A, Jha D, et al. Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease. bioRxiv. 2020; https://doi.org/10.1101/2020.05.21.109124-.
WHO. Obesity and overweight Key Facts 2020. Available online at https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight [Accessed June 8 2020)
Davis C. The Gut Microbiome and Its Role in Obesity. Nutr Today 2016; 51:167-174.
Shirakawa AK, Nagakubo D, Hieshima K, Nakayama T, Jin Z, Yoshie O. 1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells. J Immunol 2008; 180:2786–95.
Ertesvag A, Engedal N, Naderi S, Blomhoff HK. Retinoic acid stimulates the cell cycle machinery in normal T cells: involvement of retinoic acid receptor-mediated IL-2 secretion. J Immunol 2002; 169:5555–63. https://doi: 10.4049/jimmunol.169.10.5555
Simonnet A, Chetboun M, Poissy J, Raverdy, V Noulette J, Duhamel A, et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 2020; 28:7. https://doi:10.1002/oby.22831.
Williamson E, Walker A, Bhaskaran K, Bacon S, Bates C, Morton C, et al. OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. medRxiv 2020. https://doi 10.1101/2020.05.06.20092999
Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois. et al. Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission. Clin Infect Dis 2020. https://doi:10.1093/cid/ciaa415.
ICNARC Report on COVID-19 in critical care 2020. Available online at https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports [Accessed June 8 2020)
Docherty A, Harrison E, Green, Hardwick H, Pius R, Norman L, et al. (2020). Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. medRxiv. 2020. https://doi 10.1101/2020.04.23.20076042
Centres for Disease Control and Prevention. Obesity is a Common, serious and costly disease 2020. Available online at https://www.cdc.gov/obesity/data/adult.html [Accessed June 8 2020]
NHS Digital. Statistics on Obesity, Physical Activity and Diet England 2019. Available online at https://digital.nhs.uk/data-and-information/publications/ statistical/statistics-on-obesity-physical-activity-and-diet/statistics-on-obesity-physical-activity-and-diet-england-2019 [Accessed June 8 2020]
Stefan N, Birkenfeld A, Schulze M, & Ludwig D. Obesity and impaired metabolic health in patients with COVID-19 Nat Rev Endocrinol 2020; 16:341-342 https://doi 10.1038/ s41574-020-0364-6
Sattar N, McInnes I, & McMurray J. Obesity is a Risk Factor for Severe COVID-19 Infection Multiple Potential Mechanisms Circulation 2020; 142: 1 https://doi 1 0.1161/CIRCULATIONAHA.120.047659
Kassir R. Risk of COVID-19 for patients with obesity. Obes Rev. 2020.
Kalligeros M, Shehadeh F, Evangelia K, Benitez G, Beckwith C, Chan P, et al. Association of Obesity with Disease Severity among Patients with COVID-19 Obesity 2020; 28:7. https://doi: ID : 0000-0002-4624-0777
Huttunen R & Syrjänen J. Obesity and the risk and outcome of infection. Int J Obes (Lond) a.2013; 37:333-40.
Zhou P, Yang X, Shi Z. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579: 270-273 https://doi. org/10.1038/s41586-020-2012-7
Ley RE, Turnbaugh PJ, Klein S, & Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006; 444:1022e3.
Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature 2013; 500:541e6. 16.
Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J 2013; 13:514e22.
Lang JM, Eisen JA, Zivkovic AM. The microbes we eat: abundance and taxonomy of microbes consumed in a day's worth of meals for three diet types. Peer J Computer Science 2014; 2:e659.
Kaplan JL, Walker WA. Early gut colonization and subsequent obesity risk. Curr Opin Clin Nutr Metab Care 2012; 15:278e84.
Aziz Q, Dore J, Emmanuel A, Guarner F, Quigley EM. Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol Motil 2013; 25:4e15.
Furet JP, Kong LC, Tap J, Poitou C, Basdevant A, Bouillot JL, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 2010; 59:3049e57.
Kong LC, Tap J, Aron-Wisnewsky J, Pelloux V, Basdevant A, Bouillot JL, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr 2013; 98:16e24.
Castaner O, Goday A, Park YM, Lee SH, Magkos F, Shiow S, et al. The Gut Microbiome Profile in Obesity: A systematic review. Int J Endocrinol 2018. https://doi.org/10.1155/2018/4095789
Dumas A, Bernard L, Poquet Y, Lugo-Villarino G, Neyrolles O. The role of the lung microbiota and the gut–lung axis in respiratory infectious diseases’, Cell Microbiol. 2018. doi: https://10.1111/cmi.12966.
Groves H, Higham S, Moffatt M, Cox M, Tregoning. Respiratory viral infection alters the gut microbiota by inducing inappetence. mBio. 2020; 11(1): 1-17. https://doi: 10.1128/mBio.03236-19
Burini C, Kano H, Nakagaki M, Frenhani P, & Portero-McLellan. Behavioural factors of Abdominal Obesity and effects of lifestyle changes with Fiber Adequacy. New Insights Obes Gene Beyond.2017; 1: 014-022. https://doi.org/10.29328/journal.hodms.1001004
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334:105e8.
Keim NL, & Martin RJ. Dietary Whole Grain–Microbiota Interactions: Insights into Mechanisms for Human Health, Adv Nutr. 2014; 5: 556–557.
West N, Christophersen C, Pyne D, Cripps A, Conlon M, Topping D, et al. Butyrylated starch increases colonic butyrate concentration but has limited effects on immunity in healthy physically active individuals. Exerc Immunol Rev 2013 19: 102–119.
Tan DX, Reiter RJ. Mitochondria: the birthplace, battleground and the site of melatonin metabolism in cells. Melatonin Research 2019: 2:44-66.
Chellappa SL, Vujovic N, Williams JS, Scheer FAJL. Impact of circadian disruption on cardiovascular function and disease. Trends Endocrinol Metab 2019; 30(10): 767-779. https://doi.org/10.1016/j.tem.2019. 07.008.
Truong KK, Lam MT, Grandner MA, Sassoon CS, Malhotra A. Timing matters: circadian rhythm in sepsis, obstructive lung disease, obstructive sleep apnea and cancer. Ann Am Thorac Soc 2016; 13(7): 1144-1154. https://doi.org/10.1513/AnnalsATS.201602-125FR.
Geto Z, Molla MD, Challa F, Belay Y, Getahun T. Mitochondrial dynamic dysfunction as a main triggering factor for inflammation associated chronic non-communicable diseases. J Inflamm Res 2020; 13:97-107. https://doi.org/10.2147/JIR.S232009.
Davis J, Hodges V, Gillham B. Normal-Weight Adults Consume More Fiber and Fruit than Their Age- and Height-Matched Overweight/Obese Counterparts. J Amer Diet Assoc 2006; 106:6. https:// doi: 10.1016/j.jada.2006.03.013
Brown B. Vitamin D and COVID-19: ignoring the evidence costs lives. Integrative Healthcare and Applied Nutrition 2020; 10-14.
McCartney DM, & Byrne DG. Optimisation of vitamin D status for enhanced Immuno-protection against Covid-19. Ir Med J 2020; 113: 58.
Mak JW, Chan FK, & Ng SC. Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol 2020. Doi.org/10.1016/S2468-1253:30122-9
Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, & Ranasinghe P. Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes Metab Syndr 2020. Doi.org/10.1016/j.dsx.2020.04.015
GOV.UK. Tackling Obesity: Empowering Adults and Children to lead healthier lives (Policy Paper). 2020. Available from: https://www.gov.uk/government/publications/tackling-obesity-government-strategy/tackling-obesity-empowering-adults-and-children-to-live-healthier-lives (Accessed: 04/08/20)
SACN. Vitamin D and Health Report. 2016. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/537616/SACN_Vitamin_D_and_Health_report.pdf (Accessed: 01/05/20)
Lanham-New SA, Webb AR, Cashman KD, Buttriss JL, Fallowfield JL, Masud T, et al. Vitamin D and SARS-CoV-2 virus/COVID-19 disease. BMJ Nutr Prev Health. 2020;bmjnph-2020-000089.
Calder PC, Carr AC, Gombart, AF, & Eggersdorfer M. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients 2020; 12(4), 1181.
Derbyshire E, & Delange, J. COVID-19: is there a role for immunonutrition, particularly in the over 65s? BMJ Nutr Prev Health. 2020; 0:1-6.
Committee on Medical Aspects of Food Policy. Dietary Reference Values for food energy and nutrients for the United Kingdom. London, Stationery Office Books 1991.
Gibney M, Lanham-New S, Cassidy A, and Vorster H. An Introduction to Human Nutrition. 2nd edition. Oxford, Wiley-Blackwell 2009.
Mehrbod P, Amini E, & Tavassoti-Kheiri M. Antiviral activity of garlic extract on influenza virus. Iran J Virol 2009; 3: 19-23.
Panyod S, Ho CT, & Sheen LY. Dietary therapy and herbal medicine for COVID-19 prevention: A review and perspective. J Tradit Complement Med 2020. Doi.org/10.1016/j.jtcme.2020.05.004
Tong JY, Wong A, Zhu D, Fastenberg JH, Tham T. The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Reviewand Meta-analysis. Otolaryngol Head Neck Surg 2020; 163(1) 3–11. DOI: 10.1177/0194599820926473
Liu F, Zhu Y, Zhang J, et al. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial BMJ Open 2020; 10:e039519. doi: 10.1136/bmjopen-2020-039519.
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