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Vitamin D and survival in COVID-19 patients: A quasi-experimental study

Annweiler et al., The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2020.105771
Oct 2020  
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Mortality 89% Improvement Relative Risk Vitamin D  Annweiler et al.  EARLY TREATMENT Is early treatment with vitamin D beneficial for COVID-19? Retrospective 66 patients in France Lower mortality with vitamin D (p=0.0019) c19early.org Annweiler et al., The J. Steroid Bioch.., Oct 2020 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,000+ studies for 109 treatments. c19early.org
Vitamin D3 supplementation during or just before COVID-19 was associated with 68% lower mortality and less severe COVID-19 in frail elderly.
Retrospective 66 French nursing home residents, mean age 87.7, 9 control patients, and 57 that received an oral bolus of 80,000 IU vitamin D3 either in the week following the suspicion or diagnosis of COVID-19, or during the previous month. 17.5% mortality in the treatment group and 55.6% in the control group.
Bolus treatment is less effective. Pharmacokinetics and the potential side effects of high bolus doses suggest that ongoing treatment spread over time is more appropriate. Research has confirmed that lower dose regular treatment with vitamin D is more effective than intermittent high-dose bolus treatment for various conditions, including rickets and acute respiratory infections1,2. The biological mechanisms supporting these findings involve the induction of enzymes such as 24-hydroxylase and fibroblast growth factor 23 (FGF23) by high-dose bolus treatments. These enzymes play roles in inactivating vitamin D, which can paradoxically reduce levels of activated vitamin D and suppress its activation for extended periods post-dosage. Evidence indicates that 24-hydroxylase activity may remain elevated for several weeks following a bolus dose, leading to reduced levels of the activated form of vitamin D. Additionally, FGF23 levels can increase for at least three months after a large bolus dose, which also contributes to the suppression of vitamin D activation1.
This is the 4th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
risk of death, 89.0% lower, RR 0.11, p = 0.002, treatment 10 of 57 (17.5%), control 5 of 9 (55.6%), NNT 2.6, adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Annweiler et al., 13 Oct 2020, retrospective, France, peer-reviewed, mean age 87.7, 6 authors, dosage 80,000IU single dose, 80,000IU either in the week following the suspicion or diagnosis of COVID-19, or during the previous month.
This PaperVitamin DAll
Vitamin D and survival in COVID-19 patients: A quasi-experimental study
Cédric Annweiler, Bérangère Hanotte, Claire Grandin De L’eprevier, Jean-Marc Sabatier, Ludovic Lafaie, Thomas Célarier
The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2020.105771
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Authors contribution -CA has full access to all of the data in the study, takes responsibility for the data, the analyses and interpretation and has the right to publish any and all data, separate and apart from the attitudes of the sponsors. All authors have read and approved the manuscript. Declaration of Competing Interest The authors report no declarations of interest.
References
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Annweiler, Souberbielle, Schott, Decker, Berrut et al., Vitamin D in the elderly: 5 points to remember, Geriatr. Psychol. Neuropsychiatr
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Dancer, Parekh, Lax, Souza, Zheng et al., Vitamin d deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax
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Dijkman, Jebbink, Deijs, Milewska, Pyrc et al., Replication-dependent downregulation of cellular angiotensin-converting enzyme 2 protein expression by human coronavirus NL63, J. Gen. Virol
Fabbri, Infante, Ricordi, Editorial -Vitamin D status: a key modulator of innate immunity and natural defense from acute viral respiratory infections, Eur. Rev. Med. Pharmacol. Sci
Ferner, Aronson, Chloroquine and hydroxychloroquine in covid-19, BMJ, doi:10.1136/bmj.m1432
Gbinigie, Frie, Should azithromycin be used to treat COVID-19? A rapid review, BJGP Open
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Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab. Syndr
Heaney, Guidelines for optimizing design and analysis of clinical studies of nutrient effects, Nutr. Rev
Hoffmann, Kleine-Weber, Schroeder, Krüger, Herrler et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell
Hossein-Nezhad, Holick, Vitamin D for health: a global perspective, Mayo Clin. Proc
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin. Exp. Res
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Kong, Zhu, Shi, Liu, Chen et al., VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system, Mol. Endocrinol
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Meltzer, Best, Zhang, Vokes, Arora et al., Association of vitamin d status and other clinical characteristics with covid-19 test results, JAMA Netw. Open
Mendy, Apewokin, Wells, Morrow, Factors associated with hospitalization and disease severity in a racially and ethnically diverse population of COVID-19 patients, doi:10.1101/2020.06.25.20137323
Rochon, Gondan, Kieser, To test or not to test: preliminary assessment of normality when comparing two independent samples, BMC Med. Res. Methodol
Rolland, De Souto, Barreto, Van Kan, Annweiler et al., Vitamin D supplementation in older adults: searching for specific guidelines in nursing-homes, J. Nutr. Health Aging
Sterne, Angus, Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis, JAMA, doi:10.1001/jama.2020.17023
Vetel, Leroux, Ducoudray, Practical use. Geriatric autonomy group resources needs, Soins Gerontol
Yang, Zhang, Xu, Effect of Vitamin D on ACE2 and Vitamin D receptor expression in rats with LPS-induced acute lung injury, Chinese J Emerg Med
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