French recommended 200,000 IU of Vitamin D to stop COVID-19 - Jan 2021

Two articles in French after Google Translation to English

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Beneficial effect of vitamin D in Covid: what are the data?

Original in French
~~#4e4e4e:The beneficial role of vitamin D in preventing SARS-CoV-2 infection and severe forms has been suggested by numerous publications.  What data are currently available in the literature? What practical messages can we draw from this? What supplementation to offer for prevention and in the event of Covid?  Position and recommendations of experts and French national learned societies *. Exclusive!#4e4e4e"> After 12 months of viral circulation, Covid-19, linked to SARS-CoV-2, has infected millions of people around the world, killing hundreds of thousands, especially in the elderly, frail and those with chronic diseases. ¹ In the absence of an effective and accessible curative treatment to date against Covid-19, resorting to already existing molecules could help control the pandemic. The potential beneficial role of vitamin D is discussed in numerous publications. ^2-5  The objective of this position paper was to specify the data currently available in the biomedical literature on this subject, and to draw clear and pragmatic messages from them. with regard to the interest of ensuring a satisfactory vitamin D status in the general population in the context of Covid-19.Vitamin D as an aid in the prevention of SARS-CoV-2 infection?

Vitamin D deficiency, defined by a circulating concentration of 25-hydroxyvitamin D, or 25 (OH) D, less than 12 ng / mL (or 30 nmol / L), and vitamin D deficiency, defined by a concentration circulating 25 (OH) D between 12 and 20 ng / mL (or 50 nmol / L), ⁶ can affect the immune system. Indeed, vitamin D stimulates on the one hand the expression and secretion of antimicrobial peptides by monocytes / macrophages, which takes part in the defenses of the mucous membranes, but also the synthesis of anti-inflammatory cytokines while inhibiting the synthesis of cytokines. pro-inflammatory. ⁷ 

Several observational studies have reported an association between low circulating 25 (OH) D concentrations and the risk of acute respiratory infections , including influenza. ⁸ In addition, recent meta-analyzes of randomized controlled trials report a protective effect of vitamin D supplementation on respiratory tract infections, particularly in vitamin D-deficient subjects receiving daily or weekly supplementation. ^9.10Regarding Covid-19, the first reports show that the circulating concentration of 25 (OH) D is lower in infected adults than in others . ^11,12 In an ecological study, inverse correlations were found in 46 countries between vitamin D deficiency in the general population and the incidence of Covid-19. ¹³ More specifically, the existence of a vitamin D insufficiency seems to precede the incidental occurrence of Covid-19, ¹⁴ and not the other way around. Despite the lack of solid intervention data at this time , preliminary results from the Koronastudien.no study , showing in Norway that regular consumers of cod liver oil are less likely to be infected with SARS-CoV -2, ¹⁵ suggest that vitamin D supplementation could help prevent Covid-19. These observational data do not allow to prove the imputability of a low concentration of 25 (OH) D on the risk of occurrence of Covid-19 in an individual, but the known positive effects of vitamin D on the immune system raise the hypothesis that people with a satisfactory vitamin D status are better equipped not to develop the disease.Vitamin D as an aid in the prevention of severe forms of Covid-19?While Covid-19 usually only causes mild symptoms, it can also progress to an uncontrolled inflammatory reaction called a "cytokine storm", in part secondary to SARS-CoV-2 downregulation of the converting enzyme. type 2 of angiotensin (ACE2: counter-regulatory enzyme degrading angiotensin 2 into angiotensin 1-7 with antioxidant, antifibrosis and anti-inflammatory properties). The consequence is a pro-inflammatory condition associated with severe tissue damage, contributing to severe forms of Covid-19 and in particular to the occurrence of acute respiratory distress syndrome (ARDS), which is often fatal. ¹The elderly and those with co-morbidities, such as high blood pressure, diabetes or obesity, are at greater risk of developing a severe form of Covid-19.Vitamin D modulates the activity of the renin angiotensin system and the expression of ACE2 . ¹⁶ A study in rats with chemically induced ARDS showed that administration of vitamin D increased levels of mRNA and ACE2 proteins, and that rats supplemented with vitamin D had milder ARDS symptoms and lesions. pulmonary more moderate than the control rats. ¹⁷ In addition, modulation of adaptive immunity by vitamin D (stimulation of the expression of anti-inflammatory cytokines by macrophages and limitation of the production of pro-inflammatory cytokines by T helper type 17 lymphocytes) could also limit the consequences of the cytokine storm.#4e4e4e:It should also be noted that the main risk factors for vitamin D deficiency (advanced age, obesity, or chronic diseases) are very similar to the risk factors for severe forms of Covid-19. ^1,6 In the event of Covid-19, several studies have shown, taking into account the potential confounding factors, that people with a low 25 (OH) D concentration were more likely to progress to a severe form, ¹⁸ to use non-invasive ventilation, ¹⁹ to have an extended hospital stay, ¹² but also to die from Covid-19, ²⁰ including in intensive care units. ²⁰While many studies find an inverse correlation between 25 (OH) D concentration in Covid-19 patients and disease severity, this is not the case for all studies. ¹⁴ For a critical analysis of studies published up to October 15, 2020 and confounding#000000">associated with vitamin D deficiency, such as low physical activity or poor nutrition , we recommend consulting the review by Mercola et al. ⁵ Thus vitamin D insufficiency could constitute an independent risk factor of the formof Covid-19 which is potentially very interesting, because, unlike other risk factors on which there is little (or no) possibility of acting, vitamin D deficiency is very easily modified by a simple supplementation. ²¹The (rare) published intervention studies support a beneficial effect of vitamin D supplementation in  reducing the severity of symptoms in adults with Covid-19. Thus, a randomized placebo-controlled clinical trial in 40 Covid-19 patients initially deficient in vitamin D showed that a greater proportion of participants who received a high dose of vitamin D (50,000 IU / d for 7 days) did not had more SARS-CoV-2 viral RNA detectable at 21 days on oropharyngeal swabs compared to the placebo group (63% vs 21% respectively; p: 0.018). ²²On the clinical benefit side, a randomized trial reported, in 76 adults with an average age of 53 years hospitalized for Covid-19, that those who received calcifediol supplements (i.e. 25 (OH) D ) in addition to standard care against Covid-19 had significantly less frequent recourse to resuscitation than those who received only standard care (1/50 or 2% vs 13/26 or 50%; p <0.001). ²³ These results are supported by two quasi-experimental studies conducted in France during the first wave which reported less severe forms of Covid-19 and an improvement in survival of around 90% in the event of regular vitamin D3 supplementation in people elderly are hospitalized, ²⁴or residing in an accommodation establishment for dependent elderly people (EHPAD). ²⁵ An English study also reported that taking high doses of vitamin D3 (approximately 280,000 IU over a 7-day period) was associated with an 87% improvement in survival in patients hospitalized for Covid-19, regardless of initial concentrations of 25 (OH) D. ²⁶ However, the small numbers and the design of these studies justify the pursuit of large-scale randomized clinical trials. ²⁷ The above data prompts us to recommend the following actions now

- Vitamin D supplementation before any SARS-CoV-2 infection

Vitamin D supplementation is a simple, effective, safe, inexpensive measure that is reimbursed by Health Insurance. Although there is not yet clear evidence that vitamin D supplementation reduces the risk of SARS-CoV-2 infection, maintaining a satisfactory vitamin D status has benefits beyond that anyway. of Covid-19 by promoting, among other things, bone and neuromuscular health and by being associated with an improvement in the prognosis in certain cancers. ⁶ Several learned societies and groups of national and international experts have already published opinions recommending vitamin D supplementation in the context of the Covid-19 epidemic. ^28-31The British and Scottish governments have for their part planned to provide vitamin D as a preventive measure to several million fragile people. ³²In the absence of a major risk associated with supplementation at an appropriate dose ³³ and given that approximately half of the general French population has hypovitaminosis D, ³⁴ everything is now pushing to supplement vitamin D throughout the year. people at risk of hypovitaminosis D (that is to say people 80 years and over, or sick, or fragile, or dependent, or obese, or living in nursing homes), and the general population during the winter period . ²² The goal is for the majority of the general population to achieve serum 25 (OH) D concentration between 20 and 60 ng / mL. The most methodologically sound studies indicate that intakes of 1200 IU / d are necessary for this, ³⁵which, in the absence of pharmaceutical forms of vitamin D adapted to a simple daily intake, could be replaced by an intake of 50,000 IU of vitamin D3 per month . Double this dose should be prescribed for obese subjects. This attitude in fact corresponds to respecting the recommendation (excluding Covid-19) to maintain a satisfactory vitamin D status in the general population, and therefore does not require waiting for the results of randomized controlled trials dedicated to Covid-19 to be applied. The dosage of 25 (OH) D is not necessary (and is also not reimbursed in France) in this case.³⁶ 4000 IU / d, ³⁷ or 100,000 IU / month. ³⁸In some patients (patients with "fragile bones", patients with chronic renal failure with GFR <45 mL / min / 1.73 m², patients with malabsorption or in post-malabsortive bariatric bypass surgery , and elderly patients who fall), the target concentration is rather between 30 and 60 ng / mL. The 25 (OH) D assay is then necessary, and the supplementation modalities are described in the recommendations of the Group for Research and Information on Osteoporosis (GRIO). ³⁹ In elderly and very elderly patients, a recharging rate spread over several weeks may be proposed in order to avoid any undesirable effects linked to too rapid repletion. ^{21, 40}In children from 0 to 18 years old, and even if Covid-19 is often mild in this population (except for the rare cases of multisystem inflammatory syndrome), vitamin D supplementation should be continued during this pandemic, like the results found in bronchiolitis in children. ⁴¹- Vitamin D supplementation in case of proven Covid-19As we have seen above, hypovitaminosis D could be an independent risk factor for a severe form of Covid-19 which has the advantage of being very easily modified by simple supplementation. Although it seems logical, as recommended by the Academy of Medicine, ⁴²to supplement vitamin D in patients with Covid-19 based on a dosage of circulating 25 (OH) D, we are also aware that this dosage result could in many cases only be available after a delay in our view unacceptable. For example, performing an outpatient blood test incorporates several steps (making an appointment and going to the laboratory, waiting for the test result, prescription of the supplement and recovery at the pharmacy) which may discourage patients, and this especially since they should remain isolated because of their Covid-19. Similar difficulties can be encountered in nursing homes that do not have a pharmacy for indoor use. To the hospital,Even if the impact on the prevention and / or improvement of severe forms of Covid-19 is still the subject of ongoing studies,  we therefore recommend, pending the results of the ongoing controlled trials, to obtain satisfactory vitamin D status as quickly as possible in the event of infection with SARS-CoV-2 (recommendation grade 1B). We suggest prescribing in adults,  as an adjunct to the standard treatment protocols available, a loading dose of vitamin D upon diagnosis of Covid-19, for example 100,000 IU of vitamin D3 per os (200,000 IU in patients with obese patients and / or with other risk factors of severity of Covid-19) to be renewed after one week. ^2 1This supplementation makes it possible to rapidly increase the concentration of 25 (OH) D without any risk outside of rare clinical situations (sarcoidosis and other granulomatoses) or very rare (inactivating mutations of certain genes such as CYP24A1 ), and to obtain a vitamin status. D satisfactory during the critical period of approximately one month during which patients with Covid-19 can report severe forms. The potential benefit of higher dosages is currently under study. ²⁷

Read also :  Vitamin D in Covid: the answers to your questions (interview with Prof. Cédric Annweiler), January 22, 2021.

Authors* With the support of the French Association for the Fight against Rheumatism (AFLAR), the French Society of Endocrinology (SFE), the French Society of Geriatrics and Gerontology (SFGG), the French Pediatric Society (SFP), the French Society of Pediatric Endocrinology and Diabetology (SFEDP), and the Francophone Society of Nephrology, Dialysis and Transplantation (SFNDT).Cédric Annweiler ( [email protected] ), department of geriatrics, University hospital center of Angers, Angers, Jean-Pierre Aquino, general delegation of the SFGG. Justine Bacchetta, referral center for rare kidney diseases, referral center for rare calcium and phosphorus diseases, Femme Mère Enfant hospital, Bron.Pierre Bataille, nephrology service, CH of Boulogne-sur-Mer, Boulogne-sur-Mer.Stanislas Bataille, center for nephrology and kidney transplantation, Marseille.Alexandra Benachi, obstetric gynecology department, Antoine Béclère hospital, APHP, Clamart.Gilles Berrut, university hospital center of clinical gerontology, Nantes University Hospital, Nantes.Hubert Blain, geriatric ward, Montpellier University Hospital, Montpellier.Sylvie Bonin-Guillaume, department of internal medicine geriatrics, APHM, Marseille.Marc Bonnefoy, department of geriatric medicine, CHU Lyon, Pierre-Bénite.Valérie Bousson, osteoarticular radiology department, Lariboisière hospital, APHP, Paris.Béatrice Bouvard, rheumatology department, Angers University Hospital, Angers.Véronique Breuil, department of rheumatology, CHU de Nice, Nice.Olivier Bruyère, WHO Collaborating Center for the Study of Health and Aging of the Musculoskeletal System, Department of Public Health Sciences, Liège.Étienne Cavalier, department of clinical chemistry, CHU de Liège, Liège.Thomas Célarier, department of clinical gerontology, CHU de Saint-Étienne, Saint-Étienne.Olivier Chabre, endocrinology, CHU Grenoble-Alpes, Grenoble.Philipe Chanson, Department of Endocrinology and Reproductive Diseases, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre.Roland Chapurlat, Édouard Herriot hospital, Lyon.Philippe Chassagne, geriatric internal medicine department, Charles Nicolle hospital, Rouen.Charles Chazot, nephrology, NephroCare Tassin-Charcot, Sainte Foy-les-Lyon.Martine Cohen-Solal, department of rheumatology, Lariboisière hospital, APHP, Paris.Catherine Cormier, rheumatology department, Cochin hospital, APHP, Paris.Bernard Cortet, department of rheumatology, CHRU de Lille, Lille.Marie Courbebaisse, Functional Explorations Department, Georges Pompidou European Hospital, APHP, Paris.Tristan Cudennec, geriatric medicine department, Ambroise Paré hospital, Boulogne-Billancourt.Françoise Debiais, department of rheumatology, CHU de Poitiers, Poitiers. Rachel Desailloud, Department of Endocrinology, Diabetes and Nutrition, University Hospital of Amiens, Amiens.Brigitte Delemer, endocrinology, diabetology, nutrition, Robert Debré hospital, Reims University Hospital, Reims.Marc Duquenne, endocrinology, CH de Saumur, Saumur.Patrice Fardellone, department of rheumatology, University Hospital of Amiens, Amiens.Denis Fouque, department of nephrology, Lyon-Sud hospital, Lyon.Gérard Friedlander, University of Paris foundation, Paris.Thomas Funck-Brentano, department of rheumatology, Lariboisière hospital, APHP, Paris.Jean-Bernard Gauvain, geriatric short-stay service, CHR d'Orléans, Orléans. Gaetan Gavazzi, clinical geriatrics department, CHU Grenoble-Alpes, Saint-Martin-d'Hères.Laurent Grange, president of AFLAR, rheumatology department, CHU Grenoble Alpes, southern hospital, Échirolles.Olivier Guérin, president of the SFGG, department of geriatric and therapeutic medicine, CHU de Nice, NiceDominique Guerrot, president of the nephrology commission of the SFNDT, nephrology service, Rouen University Hospital, Rouen.Pascal Guggenbuhl, NUMECAN Institute (Nutrition Metabolisms and Cancer), Rennes University Hospital, Rennes.Pascal Houillier, Functional Explorations Department, Georges Pompidou European Hospital, Paris.Maryvonne Hourmant, president of the SFNDT, department of nephrology and transplantation, Nantes University Hospital, Nantes. Rachida Inaoui, department of rheumatology, Pitié-Salpêtrière, APHP, Paris.Rose-Marie Javier, department of rheumatology, Hautepierre hospital, Strasbourg.Guillaume Jean, Nephrology, NephroCare Tassin-Charcot, Sainte Foy-les-Lyon.Claude Jeandel, gerontology center, Montpellier University Hospital, Montpellier.Peter Kamenicky, Department of Endocrinology and Reproductive Diseases, Endocrine Physiology and Pathophysiology, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre.Véronique Kerlan, President of the SFE, Department of Endocrinology, Diabetes and Metabolic Diseases, Cavale Blanche Hospital, Brest.Mare-Hélène Lafage-Proust, Inserm U1059, University of Saint-Étienne, Saint-Étienne.Erick Legrand, rheumatology department, Angers University Hospital, Angers.Bruno Lesourd, Department of Geriatrics, Clermont-Ferrand University Hospital, Clermont-Ferrand.Éric Lespessailles, department of rheumatology, CHR d'Orléans, Orléans.Agnès Linglart, pediatric endocrinology department, Bicêtre hospital, APHP, Le Kremlin Bicêtre.Pierre Marès, obstetric gynecology department, Nîmes CHRU, Nîmes.Elena Paillaud, Geriatrics Department, Georges Pompidou European Hospital, APHP, Paris.Dominique Prié, BioPhyGen department, Necker-Enfants Malades hospital, Paris.Yves Rollan, Gérontopôle de Toulouse, CHU de Toulouse, Toulouse.Claire Roubaud, department of clinical gerontology, Bordeaux University Hospital, Bordeaux.Jean-Marc Sabatier, Institute of Neuro-physiopathology Marseille.Guillaume Sacco, CNRS UMR 7284 / INSERM U108, CHU de Nice, Nice. Jean-Luc -Saladin, general medicine, Le Havre.Jean-Pierre Salles, Endocrinology Unit, Bone Diseases, Children's Hospital, Toulouse University Hospital, Toulouse.Nathalie Salles, department of clinical gerontology, Bordeaux University Hospital, Bordeaux.Martin Soubrier, department of rheumatology, CHU Gabriel-Montpied, Clermont-Ferrand.Bruno Sutter, Institut Calot, Berck-sur-Mer.Achille Tchalla, clinical research and innovation unit in gerontology, CHU de Limoges, Limoges.Florence Trémollières, menopause center, Paule-de-Viguier hospital, Toulouse.Pablo Antonio Urena Torres, Department of Renal Physiology, Necker-Enfants Malades Hospital, APHP, Paris.Marie-Christine Vantyghem, endocrinology and metabolism service, C. Huriez hospital, Lille CHRU, Lille.Jean-Paul Viard, Immuno-infectiology unit, Hôtel-Dieu, APHP, Paris.Emmanuelle Vignot, Inserm UMR 1033, E. Herriot hospital, LyonDaniel Wendling, department of rheumatology, CHRU de Besançon Besançon.Jacques Young, Department of Endocrinology and Reproductive Diseases, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre.Jean-Claude Souberbielle, functional explorations department, Necker-Enfants Malades hospital, APHP, Paris.All authors meet all of the following criteria: contribution to the design or analysis and interpretation of the data; writing of the article or critical review and significant intellectual input; approval of the final version to be published.Links of interestSource of funding: none.C. Annweiler participated in ad hoc training or expertise interventions for the Mylan laboratory. H. Blain participated in ad hoc training or expertise interventions for the Mylan laboratory. F. Bruyère has received research grants and participated in ad hoc training or expertise interventions for the Amgen, Aptissen, Biophytis, IBSA, MEDA, Novartis, Sanofi, Servier, SMB, TRB Chemedica and UCB laboratories. F. Debiais participated in ad hoc training or expertise interventions for Abbott, Abbvie, Alexion, Amgen, Astrazenaca, Expanscience, Lilly, MSD, Novartis, Pfizer, Roche, Theramex, UCB laboratories.P. Fardellone has participated in occasional interventions for Arrow, Amgen, IPRAD, Lilly, Mylan, UCB laboratoriesF. Trémollieres participated in ad hoc training or expertise actions for the Amgen, Astellas, Arrow, Lilly France, Téva and Théramex laboratories.E. Vignot has participated in ad hoc training or expertise actions for AbbVie, Amgen, BMS, Janssen Cilag, Kyowa Kirin, Lilly, Novartis, Pfizer, Roche Chugaï, Theramex, UCB laboratories.D. Wendling has participated in one-off actions for AbbVie, BMS, MSD, Pfizer, Roche Chugai, Nordic Pharma, UCB, Novartis, Lilly, Grunenthal, Galapagos laboratories, and has indirect interests: Abbvie, Pfizer, Roche Chugai, MSD , UCB, Mylan, Fresenius Kabi.#f72323:

Figures and tables//www.larevuedupraticien.fr/|]#f72323:

References

• (1) Rauf A, Abu-Izneid T, Olatunde A, et al. COVID-19 Pandemic: epidemiology, etiology, conventional and non-conventional therapies. Int J Environ Res Public Health 2020; 17: 8155. 
• (2) Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020; 12: 988. 
• (3) Annweiler C, Cao Z, Sabatier JM. Point of view: should COVID-19 patients be supplemented with vitamin D? Maturitas 2020; 140: 24-6. ~
• (4) Zemb P, Bergman P, Camargo CA Jr, et al. Vitamin D deficiency and the COVID-19 pandemic. J Glob Antimicrob Resist 2020; 22: 133-4. ~
• :(5) Mercola J, Grant WB, Wagner C. Evidence regarding vitamin D and risk of COVID-19 and its severity. Nutrients 2020;
• (6) Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 2019; 40: 1109-51. 
• (7) Bishop E, Ismailova A, Dimeloe SK, Hewison M, White JH. Vitamin D and immune regulation: antibacterial, antiviral, and anti-inflammatory. JBMR Plus 2020 Aug 22; 10.1002 / jbm4.10405
• (8) Jolliffe DA, Griffiths CJ, Martineau AR. Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies. J Steroid Biochem Mol Biol 2013; 136: 321-9.
• :(9) Jolliffe DA, Camargo CA, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomized controlled trials. medRxiv 2020 Nov 25: 2020.07.14.20152728. 
• (10) Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583.
• (11) D'Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients 2020; 12: 1359.
• (12) Hernández JL, Nan D, Fernandez-Ayala M, et al. Vitamin D status in hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol Metab 2020 Oct 27; dgaa733.
• (13) Mariani J, Giménez VMM, Bergam I, et al. Association between vitamin D deficiency and COVID-19 incidence, complications, and mortality in 46 countries: an ecological study. Health Secur 2020 Dec 14. doi: 10.1089 / hs.2020.0137.
• (14) Hastie CE, Mackay DF, Ho F, et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 2020; 14: 561-5.
• (15) https: // oslo-universitetssykehus. no / om-oss / nyheter / kan-tran-forebygge-korona # facts-about-the-cod-liver-oil-study.
• (16) Kong J, Zhu X, Shi Y, et al. VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system. Mol Endocrinol 2013; 27: 2116-25.
• (17) Yang J, Zhang H, Xu J. Effect of Vitamin D on ACE2 and vitamin D receptor expression in rats with LPS-induced acute lung injury. Chinese J Emerg Med 2016; 25: 1284-9.
• (18) De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Serum 25 (OH) D level on hospital admission associated with COVID-19 stage and mortality. Am J Clin Pathol 2020. doi: 10.1093 / ajcp / aqaa252.
• (19) Baktash V, Hosack T, Patel N, et al. Vitamin D status and outcomes for hospitalized older patients with COVID-19. Postgrad Med J 2020. doi: 10.1136 / postgradmedj-2020-138712.
• (20) Vassiliou AG, Jahaj E, Pratikaki M, Orfanos SE, Dimopoulou I, Kotanidou A. Low 25-hydroxyvitamin D levels on admission to the intensive care unit may predispose COVID-19 pneumonia patients to a higher 28-day mortality risk: a pilot study on a greek ICU cohort. Nutrients 2020; 12: E3773.
• (21) Annweiler C, Souberbielle JC. Vitamin D supplementation and COVID-19: expert consensus and guidelines. Geriatr Psychol Neuropsychiatr Old 2020. doi: 10.1684 / pnv.2020.0907.
• (22) Rastogi A, Bhansali A, Khare N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomized, placebo-controlled, study (SHADE study). Postgrad Med J 2020. doi: 10.1136 / postgradmedj-2020-139065.
• (23) 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.
• (24) Annweiler G, Corvaisier M, Gautier J, et al. Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: the GERIA-COVID quasi-experimental study. Nutrients 2020; 12: E3377.
• (25) Annweiler C, Hanotte B, Grandin de l'Eprevier C, Sabatier JM, Lafaie L, Célarier T. Vitamin D and survival in COVID-19 patients: a quasi-experimental study. J Steroid Biochem Mol Biol 2020; 204: 105771.
• (26) Ling SF, Broad E, Murphy R, et al. High-dose cholecalciferol booster therapy is associated with a reduced risk of mortality in patients with COVID-19: a cross-sectional multi-center observational study. Nutrients 2020; 12: E3799.
• (27) Annweiler C, Beaudenon M, Gautier J, et al. COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial. Trials 2020. doi: 10.1186 / s13063-020-04928-5.
• (28) McCartney DM, O'Shea PM, Faul JL, et al. Vitamin D and SARS-CoV-2 infection-evolution of evidence supporting clinical practice and policy development: a position statement from the Covit-D Consortium. Ir J Med Sci 2020: 1-13.
• (29) Lanham-New SA, Webb AR, Cashman KD, et al. Vitamin D and SARS-CoV-2 virus / COVID-19 disease. BMJ Nutr Prev Health 2020; 3: 106-10.
• (30) Chhetri JK, Chan P, Arai H, et al. Prevention of COVID-19 in older adults: a brief guidance from the International Association for Gerontology and Geriatrics (IAGG) Asia / Oceania Region. J Nutr Health Aging 2020: 1-2.
• (31) http://shraga-elam.blogspot.com/2020/10/israeli-official-campaign-to-boost.html
• (32) https://www.theguardian.com/world/2020/nov/14 / COVID-uk-government-requests-guidance-on-vitamin-d-use.
• (33) Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr 2007; 85: 6-18.
• (34) Vernay M, Sponga M, Salanave B, et al. Vitamin D status of the adult population in France: the National Health Nutrition Study (ENNS, 2006-2007). Bull Epidemiol Hebd 2012; 16-7: 189-94.
• (35) Cashman K. Vitamin D requirements for the future-Lessons learned and charting a path forwards. Nutrients 2018; 10: 533.
• (36) 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.
• (37) Pittas AG, Dawson-Hughes B, Sheehan P, et al. Vitamin d supplementation and prevention of type 2 diabetes. N Engl J Med 2019; 381: 520-30. 
• (38) Malihi Z, Lawes CMM, Wu Z, et al. Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial. Am J Clin Nutr 2019; 109: 1578-87. 
• (39) Souberbielle JC, Cormier C, Cavalier E, et al. Vitamin D Supplementation in France in patients with or at risk for osteoporosis: recent data and new practices. Joint Bone Spine 2020; 87: 25-9. 
• (40) Annweiler C, Legrand E, Souberbielle JC. Vitamin D in adults: update on testing and supplementation. Geriatr Psychol Neuropsychiatr Old 2018; 16: 7-22. 
• (41) Vo P, Koppel C, Espinola JA, et al. Vitamin D Status at the time of hospitalization for bronchiolitis and its association with disease severity. J Pediatr 2018; 203: 416-422.e1. 
• (42)http://www.academie-medecine.fr/vitamin-d-and-COVID-19/?lang=en.

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Vitamin D in Covid: the answers to your questions  - Interview of Cédric Annweiler

Original in French

On January 8, we published an article - co-signed by 73 experts and 6 learned societies - on the interest of vitamin D in Covid, which generated a lot of reactions, but also questions. Why is it so difficult to prove with certainty the link between vitamin D status and susceptibility to Covid? What supplementation regimens to offer, according to the patients (obese, elderly, already supplemented or not)? What are the risks ? Interview with Prof. Cédric Annweiler, head of the geriatrics department of the University Hospital of Angers, first author of this text.~~~~ The association between vitamin D deficiency and the risk of being infected with SARS-CoV-2 or of having a severe form of Covid has been mentioned since the start of the pandemic, without formal proof. Why is it so hard to prove this link?Vitamin D has been shown to benefit bone and neuromuscular health, but its suspected (unproven) effects are manifold. Indeed, it is complicated, from observational studies , when we note an association between having hypovitaminosis D and a health event (death by Covid, for example), to specify whether the death is due to the cause of hypovitaminosis D, its consequences, or the hypovitaminosis itself . To prove this link, we need to conduct randomized clinical trials. In this pandemic context, recruitment in clinical trials is complicated, because there is a kind of "competition" between the many molecules to be tested. At Angers hospital, for example, we started a multicenter trial (10 centers in France) in April (Covit-Trial) in elderly people, to compare the effect of the administration of strong doses (400,000 IU per os in one go) versus a standard dose (50,000 IU per os in one go), from the diagnosis of Covid, on the risk of death at 14 days and on the prevention of serious forms. We had to wait 2 ^e  epidemic wave to complete inclusions and we have the results in a few weeks ...Based on the existing data, what vitamin D supplementation do you recommend?Even though there is no compelling evidence yet, there is plenty of evidence to suggest that vitamin D deficiency is an independent risk factor for severe form of Covid and death. You should know that hypovitaminosis D concerns 40 to 50% of the French population! We therefore believe that maintaining a satisfactory vitamin D status is particularly important in the context of the pandemic . To achieve this, in the consensus paper published on January 8 , we recommend supplementation of 50,000 IU per month (80,000 to 100,000 IU in the obese) throughout the year in those at risk of 'hypovitaminosis D (obese, dependent, very old or with chronic diseases) and during the winter period in the general population (from November to April). Of course, in patients with "fragile bones", chronic renal insufficiency, elderly patients who fall, or in the event of malabsorption, the 25 (OH) D must be measured and the supplementation procedures recommended by the Group of research and information on osteoporosis .

Wouldn't daily supplementation be more physiological?

Yes, theoretically, a contribution of 1000 to 1200 IU per day of vitamin D3 would be to favor compared to the spaced boluses, but in France there is no pharmaceutical form allowing a simple daily administration apart from very weakly concentrated drops used in newborns. As for food supplements, care must be taken to favor those of pharmaceutical quality. In addition, compliance is better with spaced boluses , especially in the elderly ...

And in the event of Covid, should you supplement?

The (rare) intervention studies support a beneficial effect of vitamin D supplementation in  reducing the severity of symptoms of Covid. While awaiting the results of ongoing trials, we propose to administer , as soon as Covid is diagnosed in adults, a loading dose of 100,000 IU per os (200,000 IU in obese patients and / or those having other risk factors for the severity of Covid), to be repeated after one week. 

And this, even in people regularly supplemented?

In a paper recently published by our team , we propose to prescribe a loading dose (to be renewed) of 100,000 IU in adults regularly supplemented with vitamin D and 200,000 IU in those who have not received supplementation or whose the last administration was more than 1 month old. We also propose here * a scheme in the event of a known dosage of 25 (OH) D.

What are the risks of supplementation? 

No intoxication has been described below a dose of 10,000 IU per day . The poisonings reported are most often linked to massive self-medication ingestions (in the United States, you can find vitamin D candy!), Or to prescription errors. 

Do you want to give a final message to GPs?

In this position paper bringing together 73 experts, we simply call for good medical practice to ensure that everyone has a normal level of vitamin D all year round, and especially in the event of Covid . Vitamin D supplementation is a simple, risk-free, inexpensive measure that is of interest in general, and undoubtedly particularly in the current pandemic context, even if it is not intended to replace either standard treatments or measures. barriers or vaccination . We especially do not want to fuel conspiracy theories!

Cinzia Nobile, The Practitioner's Review 

{DIV(type="p", align="justify")}#4e4e4e:* Supplementation of vitamin D3 per os upon confirmation of the diagnosis Covid-19  

(in adults, when the concentration of 25 (OH) D is known, regardless of age and severity factors Covid-19) :

• if 25 (OH) D <20 ng / mL: 1 loading dose of 200,000 IU, to be renewed after one week;
• if 25 (OH) D between 20 and 30 ng / mL: 1 loading dose of 100,000 IU, to be renewed after one week
• Si 25 (OH) D between 30 and 40 ng / mL of 50,000 IU: 1 loading dose, to be repeated after one week;
• Si 25 (OH) D> 40 ng / mL: no loading dose.

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French Consensus – 200,000 IU of Vitamin D if get COVID-19 – Dec 22, 2020 in Vitamin D Life