Rolle von Vitamin D als Präventionsmaßnahme in der COVID-19 Pandemie

Zusammenfassung

Aktuell ist die Beweislage zu Vitamin D und COVID-19 als vielversprechend, jedoch aufgrund fehlender Daten einer grossen randomisierter Interventionsstudie, als nicht umfänglich belegt zu werten. Mehrere kleinere Interventionsstudien bei COVID-19 Patientinnen und Patienten zeigen gemischte Resultate mit einem Signal, dass die einmalige hohe Bolusgabe von Vitamin D eine neutrale Wirkung hat und hingegen kleinere Dosierungen von Calcifediol in mehrtägigen Intervallen das Risiko einer Intensivmedizin-Behandlung und Mortalität vermindern könnten. Gleichzeitig zeigt die Literatur anhand grosser Beobachtungsstudien ein starkes Signal, dass Menschen mit einem Vitamin D Mangel eine höhere Anfälligkeit bezüglich einer COVID-19 Infektion und auch ein erhöhtes Risiko für schwere Verläufe und Mortalität haben. Diese epidemiologischen Studien bieten jedoch keinen Kausalitätsanspruch. Insbesondere auch weil ein Vitamin D-Mangel häufiger bei Menschen mit Übergewicht und chronischen Erkrankungen wie Diabetes und Herz-Kreislauferkrankungen vorkommt, und diese Faktoren das Risikoprofil für schwerere Verläufe der COVID-19 Infektion abbilden. Auf der mechanistischen Ebene ist Vitamin D ein etablierter Faktor der Immunmodulation, mit Hinweisen, dass eine gute Vitamin D-Versorgung im Rahmen der COVID-19 Infektion die starke Inflammationsreaktion «Zytokin-Sturm» vermindert. Nicht COVID-spezifisch, aber eine Wirkung von Vitamin D auf akute Entzündungen unterstützend, fand eine 2021 publizierte Meta-Analyse von 46 randomisierten klinischen Studien, dass die tägliche Gabe von Vitamin D verglichen zu Placebo, das Risiko jeglicher akuter Atemwegsinfekte um 20 Prozent vermindert. Nimmt man diese Beweislage in der aktuellen Krisensituation einer globalen Pandemie-Situation auf, unterstützt eine umsichtige Risiko-Benefit Analyse, dass eine unmittelbare Volksgesundheitliche Empfehlung zur täglichen Einnahme von Vitamin D als präventive Maßnahme im Rahmen der COVID-Pandemie sinnvoll ist. Dies ist analog zu den heutigen Empfehlungen zur Vitamin D-Supplementation zu sehen, da zudem in den Hochrisiko-Populationen durch die Infektion ein Zusatzrisiko eingeführt wird für die Entwicklung von Sarkopenie und Osteoporose. Ökonomisch und vom Risiko her ist die Maßnahme zudem begründet mit der kostengünstigen breiten Verfügbarkeit und dem hohen Sicherheitsprofil einer täglichen Gabe von Vitamin D.

Abstract

Currently, the evidence on vitamin D and COVID-19 is promising, but due to the lack of data from a large randomized intervention trial, the evidence is not comprehensive. Several smaller intervention studies in COVID-19 patients show inconsistent results with a signal that single high bolus doses of vitamin D have a neutral effect, whereas lower doses of calcifediol at multi-day intervals may reduce the risk of ICU treatment and mortality. At the same time, based on large observational studies, the literature shows a strong signal that people with vitamin D deficiency have a higher susceptibility with respect to COVID-19 infection and also an increased risk of complications and mortality. However, these epidemiologic studies do not provide a causal claim, especially because among other reasons vitamin D deficiency is more common in people with obesity and chronic diseases such as diabetes and cardiovascular disease, and these factors also coin the risk profile for more severe courses of COVID-19 infection.

At the mechanistic level, vitamin D is an established factor in immunomodulation, with evidence that vitamin D administration in the setting of COVID-19 infection reduces the potent inflammatory response "cytokine storm." Albeit not COVID-specific, but supporting an effect of vitamin D on acute inflammation, a meta-analysis of 46 randomized clinical trials published in 2021 found that daily administration of vitamin D, compared with placebo, reduced the risk of any acute respiratory infection by 20 percent.

Taking this evidence into the current crisis of a global pandemic situation, a prudent risk-benefit analysis supports that an immediate public health recommendation to take vitamin D daily as a preventive treatment in the context of the COVID pandemic is reasonable. This is analogous to current recommendations for vitamin D supplementation because, in addition, in high-risk populations, COVID infection introduces an important risk factor for developing sarcopenia and osteoporosis. Economically and in terms of risk, daily vitamin D supplementation is also justified by the cost-effective broad availability and its high safety profile.

Schlüsselwörter

Vitamin D - Immunomodulation - COVID-19-Infektion - Zytokin-Sturm - Muskuloskelettale Gesundheit

Key words

vitamin D - musculoskeletal health - immunomodulation - COVID-19 infection - cytokine storm

Publication History

Received: 07 December 2021
Received: 07 December 2021

Accepted: 14 December 2021

Article published online:
21 February 2022

• Literatur

• 1 Hewison M, Burke F, Evans KN. et al. Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease. J Steroid Biochem Mol Biol 2007; 103: 316-321
• 2 Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 2010; 39: 365-379 table of contents
• 3 Kearns MD, Alvarez JA, Tangpricha V. Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2014; 20: 341-351
• 4 Mazess RBB-F HA, Dawson-Hughes B. Vitamin D: Bolus is Bogus – A Narrative Review. JBMR Plus 2021; https://doi.org/10.1002/jbm4.10567
• 5 Hansdottir S, Monick MM, Hinde SL. et al. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. Journal of immunology 2008; 181: 7090-7099
• 6 Hollis BW, Wagner CL. Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab 2013; 98: 4619-4628
• 7 Gibson CC, Davis CT, Zhu W. et al. Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium. PLoS One 2015; 10: e0140370
• 8 Owens DJ, Tang JC, Bradley WJ. et al. Efficacy of High-Dose Vitamin D Supplements for Elite Athletes. Med Sci Sports Exerc 2017; 49: 349-356
• 9 Xu Y, Baylink DJ, Chen CS. et al. The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19. J Transl Med 2020; 18: 322
• 10 Kumar R, Rathi H, Haq A. et al. Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus research 2021; 292: 198235
• 11 Chung C, Silwal P, Kim I. et al. Vitamin D-Cathelicidin Axis: at the Crossroads between Protective Immunity and Pathological Inflammation during Infection. Immune Netw 2020; 20: e12
• 12 Hughes DA, Norton R. Vitamin D and respiratory health. Clinical and experimental immunology 2009; 158: 20-25
• 13 Vargas Buonfiglio LG, Cano M, Pezzulo AA. et al. Effect of vitamin D3 on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial. BMJ Open Respir Res 2017; 4: e000211
• 14 Barlow PG, Beaumont PE, Cosseau C. et al. The human cathelicidin LL-37 preferentially promotes apoptosis of infected airway epithelium. American journal of respiratory cell and molecular biology 2010; 43: 692-702
• 15 Azer SA. COVID-19: pathophysiology, diagnosis, complications and investigational therapeutics. New Microbes New Infect 2020; 37: 100738
• 16 Abrishami A, Dalili N, Mohammadi Torbati P. et al. Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study. European journal of nutrition 2021; 60: 2249-2257
• 17 Ricci A, Pagliuca A, D'Ascanio M. et al. Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients. Respir Res 2021; 22: 76
• 18 Kloc M, Ghobrial RM, Lipinska-Opalka A. et al. Effects of vitamin D on macrophages and myeloid-derived suppressor cells (MDSCs) hyperinflammatory response in the lungs of COVID-19 patients. Cell Immunol 2021; 360: 104259
• 19 Martineau AR, Jolliffe DA, Greenberg L. et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health technology assessment 2019; 23: 1-44
• 20 Jolliffe DA, Camargo CA, Sluyter JD. et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. The lancet Diabetes & endocrinology 2021; 9: 276-292
• 21 Kaufman HW, Niles JK, Kroll MH. et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One 2020; 15: e0239252
• 22 Merzon E, Tworowski D, Gorohovski A. et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J 2020; 287: 3693-3702
• 23 Brenner H. Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths-Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action. Nutrients 2021; 13
• 24 Hastie CE, Mackay DF, Ho F. et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 2020; 14: 561-565
• 25 Teshome A, Adane A, Girma B. et al. The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis. Front Public Health 2021; 9: 624559
• 26 Angelidi AM, Belanger MJ, Lorinsky MK. et al. Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients. Mayo Clinic proceedings 2021; 96: 875-886
• 27 Petrelli F, Luciani A, Perego G. et al. Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies. J Steroid Biochem Mol Biol 2021; 211: 105883
• 28 Charoenngam N, Shirvani A, Reddy N. et al. Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 2021; 27: 271-278
• 29 Bassatne A, Basbous M, Chakhtoura M. et al. The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis. Metabolism 2021; 119: 154753
• 30 Wang R, DeGruttola V, Lei Q. et al. The vitamin D for COVID-19 (VIVID) trial: A pragmatic cluster-randomized design. Contemporary clinical trials 2021; 100: 106176
• 31 Murai IH, Fernandes AL, Sales LP. et al. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA 2021; 325: 1053-1060
• 32 Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM. et al. “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”. J Steroid Biochem Mol Biol 2020; 203: 105751
• 33 Nogues X, Ovejero D, Pineda-Moncusi M. et al. Calcifediol treatment and COVID-19-related outcomes. J Clin Endocrinol Metab 2021; doi:10.1210/clinem/dgab405
• 34 Manson JE, Cook NR, Lee IM. et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2019; 380: 33-44
• 35 Bischoff-Ferrari HA, Vellas B, Rizzoli R. et al. Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial. JAMA 2020; 324: 1855-1868
• 36 The Lancet Diabetes E. Vitamin D and COVID-19: why the controversy?. The lancet Diabetes & endocrinology 2021; 9: 53
• 37 Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 1995; 61: 638S-645S