Overgewicht geeft virussen meer kans

Van de patiënten die met COVID-19 op een Nederlandse IC terechtkomen (1) lijden velen aan het ‘metaboolsyndroom’: een combinatie van overgewicht, hoge bloeddruk en een verstoorde glucose- en vethuishouding. Het is een bekende voorloper van diabetes mellitus type 2, hart- en vaatziekten en kanker (2-5). Maar waarom verhoogt het metabool syndroom bij een (virus)infectie de kans op een ernstig verloop (6,7)?

Wat het metaboolsyndroom en de risicofactoren voor ernstige COVID-19 (8-10) gemeen hebben is een toestand van chronische ‘metaflammatie’. Dit is een samenvoeging van metabolisme (stofwisseling) en inflammatie (ontsteking) (11-14). Het is een vorm van laaggradige ontsteking in het gehele lichaam met continu licht verhoogde hoeveelheden ontstekingsstoffen (cytokinen). Zo’n systemische ontstekingsreactie kost weinig energie. Dat is anders dan bij een acute infectie. Afhankelijk van de ernst, kost die zo’n 25 tot 60 procent extra energie (15-17). Chronische ‘metaflammatie’ wordt veroorzaakt door een slechte leefstijl, waaronder onvolwaardige voeding, onvoldoende beweging en slaap, ongunstige darmbacteriën en chronische stress (13,14,18). Hoe meer vetmassa, des te erger de metaflammatie(19-24).

Dat ons immuunsysteem onder deze omstandigheden hapert(19-22), wordt zichtbaar als een ziekteverwekker binnendringt (25). Bij ernstige infecties, zoals met SARS-Cov-2 (26-28), SARS-CoV (29) en influenza A (22), reageert het immuunsysteem dan zwak en/of traag. Obese COVID-19 patiënten dragen veel grotere hoeveelheden virus bij zich en raken het minder snel kwijt (26). Bij de uitbraak van de Mexicaanse griep in 2009 tekende de relatie tussen overgewicht en ernstig ziekteverloop zich ook al af (22). Het virus krijgt simpelweg meer kans. De immuunreactie is ‘gedempt’ en er is grotere kans op bijkomende infecties. Vaccinatie en antimicrobiële middelen zijn minder effectief. Ook kan het virus sneller muteren (19,20,22). Obesitas en diabetes vormden ook een risico voor ernstige infecties met SARS-CoV (30,31) en MERS-CoV (10,32,33); de voorgangers van SARS-Cov-2.

Hoe meer vetmassa, des te erger de metaflammatie

Het mechanisme is te verklaren vanuit een disbalans tussen onderdelen van de immuunreactie. Bij gezonde mensen zijn deze perfect op elkaar afgestemd. Metaflammatie zorgt ervoor dat bij ernstige virusinfecties de verschillende soorten (immuun)cellen niet goed met elkaar communiceren (10,22,25). Het gaat mis in de eerste verdedigingslijn die de vermenigvuldiging en verspreiding van het virus moet tegengegaan (10,34-40c). Het virus frustreert dit proces en grijpt zijn kans. In plaats van eerst te verdedigen stuurt het immuunsysteem steeds meer ontstekingscellen naar de longen: de plek waar het virus binnenkwam. Deze aanval veroorzaakt een lokaal slagveld met veel schade. De ontstekingsreactie versterkt zichzelf door de roep van de signaalstoffen om nog meer hulp. Er ontstaat een ‘cytokinenstorm’ en stolling. Met vaak fatale gevolgen (8,10,41,42). Lees ook: Coronapatiënten overlijden niet aan het virus per se, maar aan een overactief immuunsysteem.

Waarom vertoont een chronisch licht ontstoken lichaam geen goede immuunrespons? Dat heeft te maken met de ontregeling van de stofwisseling. De hormoonhuishouding en energiestofwisseling liggen overhoop. Door de metaflammatie ontstaat ongevoeligheid voor de hormonen insuline (6,19,21,43-45) en leptine (6,10,19,21,29,46-49). De daarbij verstoorde glucosehuishouding staat centraal in de overreactie van het immuunsysteem (50-60). Behalve van energie is het geactiveerde immuunsysteem ook sterk afhankelijk van vitamines en mineralen (61-65). Tekorten daarvan worden gezien bij ernstige COVID-19 (67-69), ouderen (68-72) en bij obesitas en diabetes (73). Uit het onderzoek is niet het detail, maar wel de conclusie allang duidelijk: het lichaam in conditie houden of brengen, is het beste advies. Het is niet te laat om gisteren te beginnen!

Prof. dr. Frits Muskiet is emeritus hoogleraar Pathofysiologie en Klinisch Chemische Analyse. Eerdere columns van Muskiet vindt u hier. De columns verschenen eerder in ons ledenmagazine Uitzicht.

                Percentage Nederlandse COVID-19 patiënten in de IC

1.             Epidemiologische situatie van SARS-CoV-2 in Nederland. Rijksinstituut voor Volksgezondheid en Milieu – RIVM 12 januari 2021, 10:00

https://www.rivm.nl/sites/default/files/2021-01/COVID-19_WebSite_rapport_wekelijks_20210112_1259_final.pdf

                Metabool syndroom

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https://pubmed.ncbi.nlm.nih.gov/16286599/

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Obesitas en ernstig COVID-19 verloop

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https://pubmed.ncbi.nlm.nih.gov/32845580/

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https://pubmed.ncbi.nlm.nih.gov/32437642/

                Metabool syndroom en ernstige COVID-19

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https://pubmed.ncbi.nlm.nih.gov/32409499/

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https://pubmed.ncbi.nlm.nih.gov/32669390/

                Metaflammatie

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https://pubmed.ncbi.nlm.nih.gov/19656309/

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https://pubmed.ncbi.nlm.nih.gov/20701689/

                Energiekosten van een infectie

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                Leefstijlfactoren bij het metabool syndroom

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                Vetmassa, immuunresponse en metaflammatie

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                Infectie bovenop metaflammatie

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                Ernstige SARS-CoV-2, SARS-CoV en influenza A infectie en zwakke/trage immuunresponse

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                Obesitas en diabetes zijn risicofactoren voor ernstige SARS-Cov en SARS-MERS infecties

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                Zwake eerste verdedigingslijn bij ernstige COVID-19 (interferon)

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                Pathofysiologie van infecties met SARS-CoV-2, SARS-CoV en MERS-CoV

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                Metaflammatie, immuunsysteem en insuline

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                Metaflammatie, immuunsysteem en leptine

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                Geactiveerd immuunsysteem, insuline en glucose

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52.           Wang S, Ma P, Zhang S, et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study [published online ahead of print, 2020 Jul 10]. Diabetologia. 2020;1-10. doi:10.1007/s00125-020-05209-1

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53.           Tucker ME. Hyperglycemia Predicts COVID-19 Death Even Without Diabetes. Medscape 13 July 2020.

https://www.medscape.com/viewarticle/933787

54.           Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, de Biagi Junior CAO, Crunfli F, Jimenez Restrepo JL, Vendramini PH, Reis-de-Oliveira G, Bispo Dos Santos K, Toledo-Teixeira DA, Parise PL, Martini MC, Marques RE, Carmo HR, Borin A, Coimbra LD, Boldrini VO, Brunetti NS, Vieira AS, Mansour E, Ulaf RG, Bernardes AF, Nunes TA, Ribeiro LC, Palma AC, Agrela MV, Moretti ML, Sposito AC, Pereira FB, Velloso LA, Vinolo MAR, Damasio A, Proença-Módena JL, Carvalho RF, Mori MA, Martins-de-Souza D, Nakaya HI, Farias AS, Moraes-Vieira PM. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis. Cell Metab. 2020 Sep 1;32(3):437-446.e5. doi: 10.1016/j.cmet.2020.07.007. Epub 2020 Jul 17. Erratum in: Cell Metab. 2020 Sep 1;32(3):498-499. PMID: 32697943; PMCID: PMC7367032.

https://pubmed.ncbi.nlm.nih.gov/32697943/

55.           Gleeson LE, O’Leary SM, Ryan D, McLaughlin AM, Sheedy FJ, Keane J. Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium tuberculosis Infection. Am J Respir Cell Mol Biol. 2018 Nov;59(5):572-579. doi: 10.1165/rcmb.2018-0162OC. PMID: 29944387.

https://pubmed.ncbi.nlm.nih.gov/29944387/

56.           Gleeson LE, Sheedy FJ. Metabolic reprogramming & inflammation: Fuelling the host response to pathogens. Semin Immunol. 2016 Oct;28(5):450-468. doi: 10.1016/j.smim.2016.10.007. Epub 2016 Oct 22. PMID: 27780657.

https://pubmed.ncbi.nlm.nih.gov/27780657/

57.           Gleeson LE, Roche HM, Sheedy FJ. Obesity, COVID-19 and innate immunometabolism. Br J Nutr. 2020 Sep 7:1-5. doi: 10.1017/S0007114520003529. Epub ahead of print. PMID: 32892755; PMCID: PMC7520638.

https://pubmed.ncbi.nlm.nih.gov/32892755/

58.           Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013 Apr 18;38(4):633-43. doi: 10.1016/j.immuni.2013.04.005. PMID: 23601682; PMCID: PMC3654249.

https://pubmed.ncbi.nlm.nih.gov/23601682/

59.           Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease. Am J Cardiol. 2007 Feb 19;99(4A):15B-26B. doi: 10.1016/j.amjcard.2006.11.003. Epub 2006 Dec 27. PMID: 17307055.

https://pubmed.ncbi.nlm.nih.gov/17307055/

60.           Donath MY. Glucose or Insulin, Which Is the Culprit in Patients with COVID-19 and Diabetes? Cell Metab. 2021 Jan 5;33(1):2-4. doi: 10.1016/j.cmet.2020.11.015. Epub 2020 Nov 24. PMID: 33248018; PMCID: PMC7685630.

https://pubmed.ncbi.nlm.nih.gov/33248018/

                Immuunsysteem en vitaminen/mineralen

61.           Amare B, Moges B, Mulu A, Yifru S, Kassu A. Quadruple burden of HIV/AIDS, tuberculosis, chronic intestinal parasitoses, and multiple micronutrient deficiency in ethiopia: a summary of available findings. Biomed Res Int. 2015;2015:598605. doi: 10.1155/2015/598605. Epub 2015 Feb 12. PMID: 25767808; PMCID: PMC4342072.

https://pubmed.ncbi.nlm.nih.gov/25767808/

62.           Maggini S, Pierre A, Calder PC. Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients. 2018 Oct 17;10(10):1531. doi: 10.3390/nu10101531. PMID: 30336639; PMCID: PMC6212925

https://pubmed.ncbi.nlm.nih.gov/30336639/

63.           Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020 Jan 16;12(1):236. doi: 10.3390/nu12010236. PMID: 31963293; PMCID: PMC7019735.

https://pubmed.ncbi.nlm.nih.gov/31963293/

64.           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 Apr 23;12(4):1181. doi: 10.3390/nu12041181. PMID: 32340216; PMCID: PMC7230749.

https://pubmed.ncbi.nlm.nih.gov/32340216/

65.           Di Renzo L, Gualtieri P, Pivari F, Soldati L, Attinà A, Leggeri C, Cinelli G, Tarsitano MG, Caparello G, Carrano E, Merra G, Pujia AM, Danieli R, De Lorenzo A. COVID-19: Is there a role for immunonutrition in obese patient? J Transl Med. 2020 Nov 7;18(1):415. doi: 10.1186/s12967-020-02594-4. PMID: 33160363; PMCID: PMC7647877.

https://pubmed.ncbi.nlm.nih.gov/33160363/

                COVID-19 en vitaminen/mineralen

66.           Heller RA, Sun Q, Hackler J, Seelig J, Seibert L, Cherkezov A, Minich WB, Seemann P, Diegmann J, Pilz M, Bachmann M, Ranjbar A, Moghaddam A, Schomburg L. Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker. Redox Biol. 2021 Jan;38:101764. doi: 10.1016/j.redox.2020.101764. Epub 2020 Oct 20. PMID: 33126054; PMCID: PMC7574778

https://pubmed.ncbi.nlm.nih.gov/33126054/

67.           Bennouar S, Cherif AB, Kessira A, Bennouar DE, Abdi S. Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19. J Am Coll Nutr. 2021 Jan 12:1-11. doi: 10.1080/07315724.2020.1856013. Epub ahead of print. PMID: 33434117; PMCID: PMC7814570.

https://pubmed.ncbi.nlm.nih.gov/33434117/

68.           Bauer JM, Morley JE. Editorial: COVID-19 in older persons: the role of nutrition. Curr Opin Clin Nutr Metab Care. 2021 Jan;24(1):1-3. doi: 10.1097/MCO.0000000000000717. PMID: 33323712; PMCID: PMC7752213.

https://pubmed.ncbi.nlm.nih.gov/33323712/

69.           Fedele D, De Francesco A, Riso S, Collo A. Obesity, malnutrition, and trace element deficiency in the coronavirus disease (COVID-19) pandemic: An overview. Nutrition. 2021 Jan;81:111016. doi: 10.1016/j.nut.2020.111016. Epub 2020 Sep 8. PMID: 33059127.

https://pubmed.ncbi.nlm.nih.gov/33059127/

                Ouderen en vitaminen/mineralen

70.           Weeden A, Remig V, Holcomb CA, Herald TJ, Baybutt RC. Vitamin and mineral supplements have a nutritionally significant impact on micronutrient intakes of older adults attending senior centers. J Nutr Elder. 2010 Apr;29(2):241-54. doi: 10.1080/01639366.2010.480897. PMID: 20473815.

https://pubmed.ncbi.nlm.nih.gov/20473815/

71.           Smit E, Winters-Stone KM, Loprinzi PD, Tang AM, Crespo CJ. Lower nutritional status and higher food insufficiency in frail older US adults. Br J Nutr. 2013 Jul 14;110(1):172-8. doi: 10.1017/S000711451200459X. Epub 2012 Nov 1. PMID: 23113895; PMCID: PMC4023911.

https://pubmed.ncbi.nlm.nih.gov/23113895/

72.           Fantacone ML, Lowry MB, Uesugi SL, Michels AJ, Choi J, Leonard SW, Gombart SK, Gombart JS, Bobe G, Gombart AF. The Effect of a Multivitamin and Mineral Supplement on Immune Function in Healthy Older Adults: A Double-Blind, Randomized, Controlled Trial. Nutrients. 2020 Aug 14;12(8):2447. doi: 10.3390/nu12082447. PMID: 32823974; PMCID: PMC7468989.

                Obesitas/diabetes en vitaminen/mineralen

https://pubmed.ncbi.nlm.nih.gov/32823974/

73.           Via M. The malnutrition of obesity: micronutrient deficiencies that promote diabetes. ISRN Endocrinol. 2012;2012:103472. doi: 10.5402/2012/103472. Epub 2012 Mar 15. PMID: 22462011; PMCID: PMC3313629.

https://pubmed.ncbi.nlm.nih.gov/22462011/

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