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2.
J Intern Med ; 292(4): 604-626, 2022 10.
Article in English | MEDLINE | ID: covidwho-1922998

ABSTRACT

Vitamin D, when activated to 1,25-dihydroxyvitamin D, is a steroid hormone that induces responses in several hundred genes, including many involved in immune responses to infection. Without supplementation, people living in temperate zones commonly become deficient in the precursor form of vitamin D, 25-hydroxyvitamin D, during winter, as do people who receive less sunlight exposure or those with darker skin pigmentation. Studies performed pre-COVID-19 have shown significant but modest reduction in upper respiratory infections in people receiving regular daily vitamin D supplementation. Vitamin D deficiency, like the risk of severe COVID-19, is linked with darker skin colour and also with obesity. Greater risk from COVID-19 has been associated with reduced ultraviolet exposure. Various studies have examined serum 25-hydroxyvitamin D levels, either historical or current, in patients with COVID-19. The results of these studies have varied but the majority have shown an association between vitamin D deficiency and increased risk of COVID-19 illness or severity. Interventional studies of vitamin D supplementation have so far been inconclusive. Trial protocols commonly allow control groups to receive low-dose supplementation that may be adequate for many. The effects of vitamin D supplementation on disease severity in patients with existing COVID-19 are further complicated by the frequent use of large bolus dose vitamin D to achieve rapid effects, even though this approach has been shown to be ineffective in other settings. As the pandemic passes into its third year, a substantial role of vitamin D deficiency in determining the risk from COVID-19 remains possible but unproven.


Subject(s)
COVID-19 , Vitamin D Deficiency , Dietary Supplements , Hormones , Humans , Sunlight , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamins/therapeutic use
3.
Am J Clin Nutr ; 115(5): 1367-1377, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1662101

ABSTRACT

BACKGROUND: Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed. OBJECTIVES: We aimed to examine the relationship between vitamin D status and mortality from COVID-19. METHODS: In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression. RESULTS: There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality. CONCLUSIONS: Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).


Subject(s)
COVID-19 , Vitamin D Deficiency , Aged , Albumins/metabolism , Female , Humans , Male , Vitamin D , Vitamin D Deficiency/complications , Vitamin D-Binding Protein , Vitamins
4.
Case Rep Crit Care ; 2021: 5541298, 2021.
Article in English | MEDLINE | ID: covidwho-1243732

ABSTRACT

Evidence exists for the use of high-flow nasal oxygen (HFNO) in the general critical care population for acute hypoxemic respiratory failure. There is discord between guidelines for hypoxemia management in COVID-19. Both noninvasive management and intubation present risk to patients and staff and potentially overwhelm hospital mechanical ventilator capacity. The use of HFNO has been particularly controversial in the UK, with oxygen infrastructure failure. We discuss our experience of managing COVID-19 with HFNO and awake self-prone positioning. We focus upon the less-usual case of an eighteen-year-old female to illustrate the type of patient where HFNO may be used when perhaps earlier intubation once was. It is important to consider the wider implications of intubation. We have used HFNO as a bridge to intubation or as definitive management. As we await clinical trial evidence, HFNO with self-prone positioning has a role in COVID-19 for certain patients. Response parameters must be set and reviewed, oxygen infrastructure considered, and potential staff droplet exposure minimised.

5.
Aliment Pharmacol Ther ; 53(1): 4-5, 2021 01.
Article in English | MEDLINE | ID: covidwho-1146855
6.
Clin Med (Lond) ; 21(2): e144-e149, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1089178

ABSTRACT

The value of vitamin D supplementation in the treatment or prevention of various conditions is often viewed with scepticism as a result of contradictory results of randomised trials. It is now becoming apparent that there is a pattern to these inconsistencies. A recent large trial has shown that high-dose intermittent bolus vitamin D therapy is ineffective at preventing rickets - the condition that is most unequivocally caused by vitamin D deficiency. There is a plausible biological explanation since high-dose bolus replacement induces long-term expression of the catabolic enzyme 24-hydroxylase and fibroblast growth factor 23, both of which have vitamin D inactivating effects. Meta-analyses of vitamin D supplementation in prevention of acute respiratory infection and trials in tuberculosis and other conditions also support efficacy of low dose daily maintenance rather than intermittent bolus dosing. This is particularly relevant during the current COVID-19 pandemic given the well-documented associations between COVID-19 risk and vitamin D deficiency. We would urge that clinicians take note of these findings and give strong support to widespread use of daily vitamin D supplementation.


Subject(s)
COVID-19 , Dietary Supplements , Respiratory Tract Infections , Rickets , Vitamin D Deficiency , Vitamin D , Humans , Pandemics , Respiratory Tract Infections/prevention & control , Rickets/prevention & control , SARS-CoV-2 , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/prevention & control
7.
Aliment Pharmacol Ther ; 52(7): 1261-1262, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-751796
8.
R Soc Open Sci ; 7(12): 201912, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1003869

ABSTRACT

Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable-links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l-1, as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021-although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800-1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU-1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain.

10.
Clin Med (Lond) ; 21(1): e48-e51, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-914784

ABSTRACT

There is growing evidence linking vitamin D deficiency with risk of COVID-19. It is therefore distressing that there is major disagreement about the optimal serum level for 25-hydroxyvitamin D (25(OH)D) and appropriate supplement dose. The UK Scientific Advisory Committee for Nutrition has set the lowest level for defining sufficiency (10 ng/ml or 25 nmol/L) of any national advisory body or scientific society and consequently recommends supplementation with 10 micrograms (400 IU) per day. We have searched for published evidence to support this but not found it. There is considerable evidence to support the higher level for sufficiency (20 ng/ml or 50 nmol/L) recommended by the European Food Safety Authority and the American Institute of Medicine and hence greater supplementation (20 micrograms or 800 IU per day). Serum 25(OH)D concentrations in the UK typically fall by around 50% through winter. We believe that governments should urgently recommend supplementation with 20-25 micrograms (800-1,000 IU) per day.


Subject(s)
COVID-19/epidemiology , Pandemics , Vitamin D Deficiency/prevention & control , Vitamin D/analogs & derivatives , Vitamin D/administration & dosage , Dietary Supplements , Dose-Response Relationship, Drug , Humans , SARS-CoV-2 , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , Vitamins/administration & dosage
11.
World J Pediatr Congenit Heart Surg ; 12(1): 43-47, 2021 01.
Article in English | MEDLINE | ID: covidwho-781410

ABSTRACT

OBJECTIVE: Response to the coronavirus/COVID-19 pandemic has resulted in several initiatives that directly impact hospital operations. There has been minimal information on how COVID-19 has affected exercise testing in pediatric patients. DESIGN: A web-based survey was designed and sent to pediatric exercise testing laboratories in the United States and Canada. Questions were designed to understand the initial and ongoing adaptations made by pediatric exercise testing laboratories in response to COVID-19. Results were analyzed as frequency data. RESULTS: There were responses from 42% (35/85) of programs, with 68% (23/34) of laboratories discontinuing all exercise testing. Of the 23 programs that discontinued testing, 15 (65%) are actively working on triage plans to reopen the exercise laboratory. Personal protective equipment use include gloves (96%; 25/26), surgical masks (88%; 23/26), N-95 masks (54%; 14/26), face shields (69%; 18/26), and gowns (62%; 16/26). Approximately 47% (15/32) of programs that typically acquire metabolic measurements reported either ceasing or modifying metabolic measurements during COVID-19. Additionally, 62% (16/26) of the programs that previously obtained pulmonary function testing reported either ceasing or modifying pulmonary function testing. Almost 60% of respondents expressed a desire for additional guidance on exercise laboratory management during COVID-19. CONCLUSIONS: Pediatric exercise testing laboratories largely closed during the early pandemic, with many of these programs either now open or working on a plan to open. Despite this, there remains heterogeneity in how to minimize exposure risks to patients and staff. Standardization of exercise testing guidelines during the COVID-19 pandemic may help reduce some of these differences.


Subject(s)
COVID-19 , Exercise Test/statistics & numerical data , Canada , Child , Health Care Surveys , Humans , Personal Protective Equipment/statistics & numerical data , United States
14.
J Neurotrauma ; 37(19): 2057-2068, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-245006

ABSTRACT

Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long-term functional outcome is neutral or negative, despite apparently promising pre-clinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects, and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multi-variate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity, and blinded outcome assessment appeared to predict neurobehavioral outcome on multi-variate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The pre-clinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting pre-clinical TBI studies in the future.


Subject(s)
Brain Injuries, Traumatic/therapy , Hypothermia, Induced , Animals , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/etiology , Disease Models, Animal , Humans , Outcome Assessment, Health Care , Pragmatic Clinical Trials as Topic
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