COVID-19 et Supplémentation en vitamine D / COVID-19 and Supplementation vitamin D

CONTEXTE: Le présent document ainsi que les constats qu'il énonce ont été rédigés dans le contexte de la crise sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. L'objectif est de réaliser une recension des données publiées et de mobiliser les savoirs clés afin d'informer les décideurs publics et les professionnels de la santé et des services sociaux. Bien que les constats reposent sur un repérage exhaustif des données scientifiques publiées, l'évaluation de la qualité méthodologique des études et une appréciation du niveau de preuve scientifique par paramètre clinique d'intérêt, le processus ne repose pas sur une méthode systématique ni une validation externe selon les normes habituelles à l'INESSS. Par ailleurs, les positions ne découlent pas d'un processus de consultation élaboré. Dans les circonstances d'une telle crise de santé publique, l'INESSS reste à l'affût de toutes nouvelles données, qu'elles soient de nature scientifique ou contextuelle, susceptibles de lui faire modifier cette réponse. MÉTHODOLOGIE: Questions d'évaluation Comparativement aux standards de soins, est-ce qu'un supplément de vitamine D, chez les personnes ayant ou non une déficience ou une insuffisance, est efficace et sécuritaire pour, prévenir l'infection et les manifestations cliniques de la COVID-19? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce n'exige pas une hospitalisation? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce exige o une hospitalisation sans le recours à une oxygénothérapie; o une hospitalisation avec le recours à une oxygénothérapie non invasive (oxygène à faible débit, à haut débit, ventilation mécanique non invasive); o une hospitalisation avec le recours à une oxygénothérapie invasive (ventilation mécanique invasive, ECMO)? Quelle est la position des sociétés savantes, des agences règlementaires, des agences de santé publique et des agences d'évaluation des technologies en santé sur l'usage d'un supplément de vitamine D dans la prévention et le traitement de la COVID-19? Type de revue de littérature: Revue rapide. RÉSULTATS: ÉTAT ACTUEL DES CONNAISSANCES SCIENTIFIQUES. Données cliniques sur l'efficacité de la supplémentation en vitamine D dans le contexte de la COVID-19. Depuis l'instauration en mars 2020 de la recherche systématique en continu de la littérature scientifique sur les médicaments à visée thérapeutique, 42 027 notices ont été recensées dont 113 études cliniques où l'intervention étudiée portait sur la vitamine D. De ce nombre, 3 ECRA [Murai et al., 2021; Castillo et al., 2020; Rastogi et al., 2020] ont été retenus. Ces études sont décrites ci-dessous en fonction du type de prise en charge, soit la prophylaxie pré/post-exposition, ou le traitement de patient dont l'état de santé requiert ou non une hospitalisation. Seuls les paramètres d'intérêts sur l'évolution de la charge virale, l'amélioration ou la résolution des symptômes ou d'évolution clinique, le pronostic, l'innocuité ou la mortalité sont présentés. Supplémentation en vitamine D en prophylaxie: En date du 24 février 2021, aucun ECRA ni aucune étude observationnelle publiés n'ont été retracés par la recherche de la littérature scientifique sur les bénéfices cliniques associés à l'usage de vitamine D en prophylaxie pré- ou post- exposition au SARS-CoV-2. Par contre, il y a quelques essais cliniques actuellement enregistrés sur le site de ClinicalTrials, dont un essai comparatif à répartition aléatoire multicentrique à triple insu (PROTECT6 ) en cours de réalisation au sein de deux hôpitaux du Québec. Le principal objectif de cet essai est d'étudier les effets prophylactiques d'une supplémentation à hautes doses de vitamine D3 per os (bolus 100 000 UI suivi de 10 000 UI par semaine pendant 16 semaines) chez les travailleurs de la santé exposés à la COVID-19. Il est prévu que l'essai se termine en juin 2021. DISCUSSION: Au terme des travaux, il ressort qu'aucun ECRA ni aucune étude observationnelle publiés dans la littérature ne permettent d'évaluer l'effet d'une supplémentation en vitamine D utilisée en prophylaxie pré- ou post- exposition au SRAS-CoV-2 ni dans le traitement des sujets COVID-19 confirmés dont l'état n'exige pas une hospitalisation. Toutefois, en ce qui concerne les personnes atteintes de la COVID-19 dont l'état de santé requiert une hospitalisation, l'état actuel des connaissances scientifiques suggère qu'une supplémentation en vitamine D3 ne permet pas de réduire la durée d'hospitalisation et le nombre de nouveaux sujets ayant besoin de ventilation mécanique invasive et ne permet pas d'établir un lien en une supplémentation en vitamine D et les admissions aux soins intensifs ou la mortalité. Un supplément en vitamine D3 à raison de 60 000 UI par jour pendant 8 ou 14 jours, chez des personnes ayant une déficience en vitamine D, pourrait cependant permettre d'augmenter la proportion de sujets avec une négativation de la RTPCR sans toutefois avoir d'impact sur la durée moyenne avant la négativation de celle-ci. Il est toutefois important de souligner que les trois ECRA ont été réalisés sur des populations distinctes, hospitalisées pour une COVID-19 de sévérité variable, et avec différentes posologies et formes de vitamine D3 (calcifédiol ou cholécalciférol). Les profils d'innocuité et d'interactions médicamenteuses de la vitamine D sont aujourd'hui bien connus dans plusieurs contextes extérieurs à la COVID-19 [Euro-Pharm International Canada, 2018; Vifor Pharma, 2018]. Fondé sur 2 ECRA à double insu conduits au Brésil et en Inde dans le contexte de la COVID-19, la supplémentation de vitamine D3 à haute dose semble sécuritaire lorsque cette dernière est administrée en prise unique ou de manière quotidienne pendant une durée maximale de 14 jours chez des sujets adultes atteints de la COVID-19 et hospitalisés. Dans tous les documents consultés présentant des positions ou des recommandations cliniques, aucune organisation ne se prononce en faveur de l'usage de la vitamine D en prévention d'une infection par le SARS-CoV-2 ou comme traitement d'une telle infection en dehors d'un essai clinique, en raison d'une insuffisance de preuves. Compte tenu des risques potentiels d'effets indésirables, un suivi régulier des personnes recevant des doses de vitamine D supérieures à 4 000 UI par jour est également recommandé. Cette réponse rapide de l'INESSS comporte certaines limites qui méritent d'être soulignées. D'abord, l'analyse du niveau de preuve scientifique est basée sur 3 études primaires de type ECRA, elles aussi, empreintes de biais et de limites méthodologiques (y compris des déséquilibres dans les caractéristiques des sujets, dans la puissance statistique et dans les posologies et formes de vitamine D3 utilisées) affectant la confiance envers les résultats actuellement disponibles. Par ailleurs, le manque de résultats ne permet pas de conclure quant à d'éventuelles différences d'efficacité entre des sujets à différents stades de la maladie ou avec des niveaux de vitamine D différents au début des études (taux normal, insuffisance, déficience). Enfin, les constats ne découlent pas d'un processus de consultation élaboré. À la suite de l'analyse effectuée, la tendance pointe vers une absence de bénéfice de la supplémentation en vitamine D ayant 2021-03-08 15:16 22 un réel impact sur l'évolution clinique ou la mortalité liée à la COVID-19. Il faudra toutefois attendre les résultats d'ECRA supplémentaires dont la qualité méthodologique sera jugée acceptable avant d'infirmer ou confirmer une absence de bénéfices. L'efficacité et l'innocuité d'une supplémentation en vitamine D sont présentement évaluées dans plusieurs études cliniques en cours, soit en prophylaxie, chez des patients non hospitalisés ou chez des patients hospitalisés9 . En demeurant à l'affût de nouvelles données scientifiques, cette réponse rapide permet d'informer les professionnels de la santé et de les soutenir dans leur prise de décision clinique dans le contexte de la pandémie actuelle.

Possible role of vitamin D in Covid-19 infection in pediatric population.

PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and ß-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.

Mini-Review on the Roles of Vitamin C, Vitamin D, and Selenium in the Immune System against COVID-19.

Low levels of micronutrients have been associated with adverse clinical outcomes during viral infections. Therefore, to maximize the nutritional defense against infections, a daily allowance of vitamins and trace elements for malnourished patients at risk of or diagnosed with coronavirus disease 2019 (COVID-19) may be beneficial. Recent studies on COVID-19 patients have shown that vitamin D and selenium deficiencies are evident in patients with acute respiratory tract infections. Vitamin D improves the physical barrier against viruses and stimulates the production of antimicrobial peptides. It may prevent cytokine storms by decreasing the production of inflammatory cytokines. Selenium enhances the function of cytotoxic effector cells. Furthermore, selenium is important for maintaining T cell maturation and functions, as well as for T cell-dependent antibody production. Vitamin C is considered an antiviral agent as it increases immunity. Administration of vitamin C increased the survival rate of COVID-19 patients by attenuating excessive activation of the immune response. Vitamin C increases antiviral cytokines and free radical formation, decreasing viral yield. It also attenuates excessive inflammatory responses and hyperactivation of immune cells. In this mini-review, the roles of vitamin C, vitamin D, and selenium in the immune system are discussed in relation to COVID-19.

Vitamin D3 as Potential Treatment Adjuncts for COVID-19.

Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the "cytokine storm", promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.

Covid-19 and vit-d: Disease mortality negatively correlates with sunlight exposure.

The novel COVID-19 disease is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a new virus of the coronavirus family, SARS-CoV-2. Alike with other coronaviruses, some studies show a COVID-19 neurotropism, inducing de-myelination lesions as encountered in Guillain-Barré syndrome. In particular, an Italian report concluded that there is a significant vitamin D deficiency in COVID-19 infected patients. In the current study, we applied a Pearson correlation test to public health as well as weather data, in order to assess the linear relationship between COVID-19 mortality rate and the sunlight exposure. For instance in continental metropolitan France, average annual sunlight hours are significantly (for a p-value of 1.532 × 10-32) correlated to the COVID-19 mortality rate, with a Pearson coefficient of -0.636. This correlation hints at a protective effect of sunlight exposure against COVID-19 mortality. This paper is proposed to foster academic discussion and its hypotheses and conclusions need to be confirmed by further research.

Scientific Rationale for a Bottom-Up Approach to Target the Host Response in Order to Try and Reduce the Numbers Presenting With Adult Respiratory Distress Syndrome Associated With COVID-19. Is There a Role for Statins and COX-2 Inhibitors in the Prevention and Early Treatment of the Disease?

The inflammatory response to and the subsequent development of Adult Respiratory Distress Syndrome (ARDS) is considered to underpin COVID-19 pathogenesis. With a developing world catastrophe, we need to examine our known therapeutic stocks, to assess suitability for prevention and/or treatment of this pro-inflammatory virus. Analyzing commonly available and inexpensive immunomodulatory and anti-inflammatory medications to assess their possible effectiveness in improving the host response to COVID-19, this paper recommends the following: (1) optimize current health-cease (reduce) smoking, ensure adequate hypertension and diabetes control, continue exercising; (2) start on an HMG CoA reductase inhibitor "statin" for its immunomodulatory and anti-inflammatory properties, which may reduce the mortality associated with ARDS; and (3) consider using Diclofenac (or other COX-2 inhibition medications) for its anti-inflammatory and virus toxicity properties. For purposes of effectiveness, this needs to be in the early course of the disease (post infection and/or symptom presentation) and given in a high dose. The downsides to these recommended interventions are considered manageable at this stage of the pandemic.

The ethics and value of contact tracing apps: International insights and implications for Scotland's COVID-19 response.

The COVID-19 pandemic has put health systems, economies and societies under unprecedented strain, calling for innovative approaches. Scotland's government, like those elsewhere, is facing difficult decisions about how to deploy digital technologies and data to help contain, control and manage the disease, while also respecting citizens' rights. This paper explores the ethical challenges presented by these methods, with particular emphasis on mobile apps associated with contact tracing. Drawing on UK and international experiences, it examines issues such as public trust, data privacy and technology design; how changing disease threats and contextual factors can affect the balance between public benefits and risks; and the importance of transparency, accountability and stakeholder participation for the trustworthiness and good-governance of digital systems and strategies. Analysis of recent technology debates, controversial programmes and emerging outcomes in comparable countries implementing contact tracing apps, reveals sociotechnical complexities and unexpected paradoxes that warrant further study and underlines the need for holistic, inclusive and adaptive strategies. The paper also considers the potential role of these apps as Scotland transitions to the 'new normal', outlines challenges and opportunities for public engagement, and poses a set of ethical questions to inform decision-making at multiple levels, from software design to institutional governance.

Covid-19 pandemic and the motivations for demanding health service in indigenous villages.

OBJECTIVE: To discuss the fundamental aspects in the establishment of preventive measures to tackle covid-19 among indigenous people in view of the motivations for seeking health care in villages of the Terra Indígena Buriti, Mato Grosso do Sul, Brazil. METHODS: Theoretical-reflective study based on assumptions of the National Health System and previous ethnographic research that enabled the identification of the motivations to seek health care in Buriti villages. RESULTS: Indigenous people seek health centers for health care programs assistance, treatment of cases they cannot resolve and to chat. Such motivations were the basis for discussing the indigenization process in the confrontation of the new coronavirus pandemic in indigenous lands. FINAL CONSIDERATIONS: The motivations for seeking health care show the physical and social vulnerability of the Terena ethnicity. The effectiveness of the social isolation measure in the villages depends on the dialogue with indigenous leaders, professional engagement and intersectoral actions.

COVID-19 and 'immune boosting' on the internet: a content analysis of Google search results.

OBJECTIVE: The spread of misinformation has accompanied the coronavirus pandemic, including topics such as immune boosting to prevent COVID-19. This study explores how immune boosting is portrayed on the internet during the COVID-19 pandemic. DESIGN: Content analysis. METHODS: We compiled a dataset of 227 webpages from Google searches in Canada and the USA using the phrase 'boost immunity' AND 'coronavirus' on 1 April 2020. We coded webpages for typology and portrayal of immune boosting and supplements. We recorded mentions of microbiome, whether the webpage was selling or advertising an immune boosting product or service, and suggested strategies for boosting immunity. RESULTS: No significant differences were found between webpages that appeared in the searches in Canada and the USA. The most common types of webpages were from news (40.5%) and commercial (24.7%) websites. The concept of immune boosting was portrayed as beneficial for avoiding COVID-19 in 85.5% of webpages and supplements were portrayed as beneficial in 40% of the webpages, but commercial sites were more likely to have these portrayals. The top immune boosting strategies were vitamin C (34.8%), diet (34.4%), sleep (34.4%), exercise (30.8%) and zinc (26.9%). Less than 10% of the webpages provide any critique of the concept of immune boosting. CONCLUSIONS: Pairing evidence-based advice for maintaining one's health (eg, healthy diet, exercise, sleep) with the phrase immune boosting and strategies lacking in evidence may inadvertently help to legitimise the concept, making it a powerful marketing tool. Results demonstrate how the spread of misinformation is complex and often more subtle than blatant fraudulent claims.

Impact of non-pharmaceutical interventions for reducing transmission of COVID-19: a systematic review and meta-analysis protocol.

INTRODUCTION: Implementing non-pharmaceutical interventions (NPIs) protect the public from COVID-19. However, the impact of NPIs has been inconsistent and remains unclear. This study, therefore, aims to measure the impact of major NPIs (social distancing, social isolation and quarantine) on reducing COVID-19 transmission. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis research of both randomised and non-randomised controlled trials. We will undertake a systematic search of: MEDLINE, Embase, Allied & Complementary Medicine, COVID-19 Research, WHO database on COVID-19, ClinicalTrails.Gov for clinical trials on COVID-19, Cochrane Resources on Coronavirus (COVID-19), Oxford COVID-19 Evidence Service and Google Scholar for published and unpublished literatures on COVID-19 including preprint engines such as medRxiv, bioRxiv, Litcovid and SSRN for unpublished studies on COVID-19 and will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Outcomes of interest for impact analysis will include the reduction of COVID-19 transmission, avoiding crowds and restricting movement, isolating ill and psychological impacts. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist has been used for this protocol. For quality of included studies, we will use the Cochrane Collaboration's tool for assessing risk of bias for randomised controlled trials and the Newcastle-Ottawa Scale for observational studies. The Grading of Recommendations Assessment, Development and Evaluation approach will grade the certainty of the evidence for all outcome measures across studies. Random-effects model for meta-analysis will measure the effect size of NPIs or the strengths of relationships. For quantitative data, risk ratio or OR, absolute risk difference (for dichotomous outcome data), or mean difference or standardised mean difference (for continuous data) and their 95% CIs will be calculated. Where statistical pooling is not possible, a narrative synthesis will be conducted for the included studies. To assess the heterogeneity of effects, I2 together with the observed effects will be evaluated to provide the true effects in the analysis. ETHICS AND DISSEMINATION: Formal ethical approval from an institutional review board or research ethics committee is not required as primary data will not be collected. The final results of this study will be published in an open-access peer-reviewed journal, and abstract will be presented at suitable national/international conferences or workshops. We will also share important information with public health authorities as well as with the WHO. In addition, we may post the submitted manuscript under review to medRxiv, or other relevant preprint servers. TRIAL REGISTRATION NUMBER: CRD42020207338.

Do Low Vitamin D Levels Increase COVID-19 Risk?

Two recent studies arrive at different conclusions.

Potential benefits of Yoga in pregnancy-related complications during the COVID-19 pandemic and implications for working women.

BACKGROUND: Pregnancy is a vulnerable period of growth and enrichment along with many physiological and psychological challenges. These changes can lead to complications if compounded by external stress and anxiety. COVID-19 has emerged as a chief stressor among the general population and is a serious threat among vulnerable populations. Therefore, there is a need for stress management tools, such as Yoga and physical exercises, both at home and at work. These can be adopted during the pandemic with proper maintenance of social distancing. OBJECTIVE: To evaluate and compile literature that has reported the health outcomes of Yoga intervention on pregnancy at the workplace and analyzes both the restrictions as well as advantages of its beneficial effects in comparison to physical exercises. METHODOLOGY: A comprehensive literature review was conducted utilizing PubMed and Google Scholar. The keywords used for the search include "Yoga", "work", "complications", "physical exercise", "drugs" and "COVID" indifferent permutations and combinations with "pregnancy". We compiled the literature with respect to pregnancy complications and the effects of drugs, physical activity and Yoga for preventing these complications. RESULTS: We noted that pregnancy-related complications are becoming more prevalent because of a sedentary lifestyle, restricted physical activity and growing stress. In such situations, a home or workplace Yoga protocol can combine both exercise and mindfulness-based alleviation of anxiety for both working and non-working women. CONCLUSION: Yoga can be effective for combating stress and anxiety besides boosting immunity in pregnant working women confronted with the COVID-19 pandemic.

The first cohort of the COVID-19 patients in Vietnam and the national response to the pandemic.

The COVID-19 pandemic is a novel infectious disease pandemic with the agent SARS-CoV-2 virus which is currently affecting and causing damage globally. The outbreak has been crossing over 200 countries in the world. In the situation of the outbreak of COVID-19, Vietnam has first sixteen typical cases confirmed positive updated to Feb 28th, 2020. After completely applying the medical prevention and active control, Vietnam has the ability to take control of the outbreak of COVID-19 as a recent of WHO assessment. Vietnam has been reported as an effective country for prevention and control the outbreak of COVID-19. We retroactive reviewed our experience with 16 positive cases isolation. This article aims to present the first cohort of COVID-19 patients updated to Feb 28th, 2020 in Vietnam and sharing the national response to the pandemic.

The Battle Between Politics and Science Is Costing Us a Timely Victory Over the COVID-19 Pandemic.

Against the backdrop of the COVID-19 pandemic, the author discusses what he views as a persistent tension between the nature and aims of politics vs science. He outlines a call to action for osteopathic physicians to stand with science, advocate for best practices, undertake dialogue with local and state health authorities, and act as role models for colleagues and patients alike.

Omega-3 fatty acids in the psychological and physiological resilience against COVID-19.

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.