This website is intended for healthcare professionals only.

Newsletter          
Hospital Healthcare Europe
HOPE LOGO
Hospital Healthcare Europe

Press Releases

Take a look at a selection of our recent media coverage:

Statin induced muscle symptoms not improved with vitamin D

5th December 2022

Statin induced muscle symptoms may be helped by vitamin D but a recent trial found that supplementing did not affect the discontinuation rate

Supplementing with vitamin D did not reduce statin induced muscle aches and pains or discontinuation rates compared to placebo according to the results of a randomised trial by US researchers.

Statins therapy is a recognised treatment for reducing the risk of all-cause and cardiovascular mortality and cardiovascular events and these benefits are even greater among those with a higher baseline risk. Nevertheless, it has become widely recognised that statin induced muscular symptoms is a common real-world problem, even with average dosage statin therapy and which has a large impact on patients’ life. Moreover, these effects can lead to discontinuation and therefore reducing the cardiovascular disease benefit. In a 2015 meta-analysis, it was shown that low vitamin D levels were associated with myalgia in patients on statin therapy. In fact, a prospective study found in many cases, statin intolerance due to myalgia, myositis or myopathy in patients with low serum vitamin D levels, could be resolved by supplementing with the vitamin. However, to date, no randomised, placebo-controlled trials have addressed the value of supplementing with vitamin D on either statin induced muscular symptoms or drug discontinuation rates.

The current study was part of the VITAL trial that explored the value of both vitamin D and omega-3 fatty acids on cardiovascular and cancer outcomes. Researchers identified a sub cohort within VITAL prescribed statin therapy and who had been randomised to vitamin D or placebo. In both cohorts, baseline vitamin D levels had been recorded. The primary endpoint of the study was the development of muscle symptoms while taking a statin and the main secondary endpoint was statin discontinuation.

Statin induced muscle symptoms and vitamin D

Statins were initiated in 1033 participants with a mean age of 66.8 years (49% female) and 1050 individuals were assigned to placebo and followed for a mean of 4.8 years.

During follow-up, statin induced muscle symptoms were reported by 31% of those assigned to vitamin D and placebo, giving an adjusted odds ratio, OR of 0.97 (95% CI 0.80 – 1.18, p = 0.78).

In addition, the discontinuation rate was 13% in both groups (OR = 1.04, 95% CI 0.80 – 1.35, p = 0.78). When looking at the incidence of statin related muscle symptoms and serum vitamin D levels, a similar proportion of participants in both groups reported muscle problems where levels were either below 20 ng/mL or below 30 ng/mL.

The authors concluded that vitamin D supplementation did not prevent statin associated muscle symptoms or reduce the rate of drug discontinuation irrespective of pre-treatment vitamin D levels.

Citation
Hlatky MA et al. Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo. JAMA Cardio 2022

Review suggests serum vitamin D levels might protect against developing COVID-19

21st November 2022

Serum vitamin D levels may protect against the development of COVID-19 but appears to have little impact on other outcomes such as mortality

Serum vitamin D levels might offer some protection against infection from COVID-19 but there is a lack of positive evidence for other outcomes such as reducing disease severity or mortality, according to the conclusion of a systematic review (available as a preprint) by researchers from the Philadelphia College of Osteopathic Medicine, US.

Much has been made of the potential protective role of higher serum vitamin D levels and COVID-19. This arises from studies showing how vitamin D affects multiple immune system mechanisms including a dampening of the entry and replication of the virus, reducing concentrations of pro-inflammatory cytokines, raising levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activation of defensive cells such as macrophages. Much of the hope for the vitamin comes from a 2017 systematic review in which the vitamin was given as a supplement, concluding that it protected against acute respiratory tract infections and how those who had a deficiency of vitamin D or who did not receive bolus doses, experienced the most benefit. Moreover, throughout the COVID-19 pandemic, emerging data has demonstrated an association between deficiency of vitamin D and the severity of infection and subsequent post-infection mortality.

In the present review, the US researchers looked at studies assessing vitamin D levels and how this impacted on the level of infection, levels of inflammatory markers, disease severity and mortality. The team compared the effects of sufficient vitamin D (serum 25(OH) D levels > 30 ng/ml, insufficient (21 – 29 ng/ml) and deficient levels (< 20 ng/ml).

Serum vitamin D levels and COVID-19 outcomes

A total of 19 studies were included. Among those who tested positive for COVID-19, the median vitamin D levels were 27.08 nmol/L and 48.67 nmol/L in those who were negative. The authors termed this difference to be ‘near significant’ (p = 0.059).

In some of the included studies, elevated levels of C-Reactive Protein (which is a marker for inflammation) and therefore disease severity, were found to be significantly associated with low levels of vitamin D. In one such study, inpatients with a median serum vitamin D levels < 12 ng/ml had more severe disease compared to those with median values > 12 ng/ml (p = 0.004). However, this was not a consistent finding.

In relation to length of hospital stay (used as a measure of disease severity), studies were mixed, with some highlighting a significant association and others no difference. In fact, median vitamin D levels were 45.02 nmol/L in those categorised as having moderate severity disease and 38.08 nmol/L in those with severe disease and this difference was not significant (p = 0.22). Finally, the differences in serum levels between those who survived and died of COVID-19 were also not significantly different.

The authors concluded that there seemed to be a correlation between vitamin D deficiency and the likelihood of developing severe illness from COVID-19 when observing studies individually but that when comparing studies on a larger scale, the significant difference seemed to fade.

Citation
Kersh L et al. What is the Impact of Vitamin D Levels on COVID-19 Severity?: A Systematic Review. Research Square 2022

RCT finds no reduction in cataract surgery after long-term high-dose vitamin D

7th November 2022

The need for cataract surgery was not reduced over a 5-year period among individuals given high-dose vitamin D compared to matching placebo

The need for cataract surgery among older adults did not reduce after 5-years of routinely supplementing with high-dose vitamin D compared to placebo according to the findings of a randomised trial by Australian researchers.

A cataract is a clouding or opacification of the normally clear lens of the eye or its capsule that obscures the passage of light through the lens to the retina. It is an extremely common condition with an estimated 95 million people worldwide affected and represents the leading cause of blindness in middle-income and low-income countries. Cataract surgery is a common medical procedure involving the extraction of the lens from an eye and data show that the procedure was conducted round 4.5 million times in 2016 across the EU Member States. The potential role of vitamin D in the development of a cataract has been suggested due to the presence of its receptors within the eye and research on how expression of the receptor plays a significant role during retinal vascular development, especially during maturation of retinal vasculature. Additionally, observational data has shown that the risk of age-related cataract is reduced in men with higher serum 25-hydroxyvitamin D levels after adjusting for potential confounding factors. Nevertheless, this has not been a consistent finding with other study concluding that there does not appear to be a role for vitamin D in cataractogenesis among men. But as the currently available evidence is largely observational in nature, the Australian team undertook a randomised, controlled trial to determine if long-term supplementation with high-dose vitamin D might reduce the incidence of cataracts using the need for cataract surgery as a surrogate marker.

The Australian team used data generated from the D-Health trial, which enrolled adults aged between 60 and 79 years of age and which was designed to examine the effect of high-dose vitamin D (60,000 IU per month) on all-cause mortality. However, participant data collected included demographics and existing health conditions although baseline ophthalmic examinations were not included. The researchers set the primary outcome as the need for cataract surgery and although vitamin D levels were not measured in all participants, the researchers developed a model to predict baseline levels using data collected from a random sample of the participants.

Cataract surgery and vitamin D levels

A total of 19,925 individuals with a mean age of 69.3 years (46% female) were included and randomised to vitamin D (9941) or matching placebo and were followed for a median of 5 years.

A total of 3668 (18.4%) of the entire cohort underwent cataract surgery during follow-up and the rate was similar between the two groups (Hazard Ratio, HR = 1.02, 95% CI 0.95 – 1.09). In subgroup analysis, the incidence of cataract was higher among women (HR = 1.22, 95% CI 1.13 – 1.29) and in those aged over 75 years compared to ages 60 – 64 (HR = 3.53). There was also no difference between individuals with estimated vitamin D levels predicted to be either greater than or less than 50 nmol/L.

The authors concluded that there was no evidence to support the routine use of vitamin D in older adults as a strategy to reduce the need for cataract surgery.

Citation
Rahman ST et al. Vitamin D Supplementation and the Incidence of Cataract Surgery in Older Australian Adults Ophthalmology 2022

Low vitamin D levels linked to worse overall survival in invasive melanoma

21st September 2022

Low vitamin D levels in those with invasive melanoma are associated with a lower overall rate of survival but not melanoma specific survival

Low vitamin D levels (LVD) are independently associated with a worse overall survival among patients with invasive melanoma but not melanoma specific survival according to the findings of a retrospective analysis by Spanish researchers presented at the 31st Dermatology and Venereology congress and simultaneously published in the journal Melanoma Research.

Melanoma of the skin is the 17th most common cancer worldwide and there were more than 150,000 new cases in 2020. In recent years it has been suggested that there is positive association between circulating levels of vitamin D (Vit D) and the risk of melanoma although this is confounded by sun exposure. However, single nucleotide polymorphisms in the Vit D receptor gene may alter the expression or the function of the VDR protein leading to various diseases, including melanoma. In the present study, the Spanish team sought to analyse the relationship between Vit D levels and prognosis in patients with a melanoma. The team retrospectively examined patients with an invasive melanoma at a university hospital in Barcelona and assessed their Vit D level. Individuals were categorised as having either LVD (defined as < 10 ng/ml) or equal to or higher than 10 ng/ml. The team examined differences in overall survival (OS) and what they termed ‘melanoma-specific survival (MSS) based on levels of vitamin D and used multivariate survival analysis, adjusted for age, gender, Breslow index and season when the test was done, since this affected the intensity of ultraviolet radiation.

Low vitamin D levels and overall survival

A total of 264 invasive melanoma patients with a mean age of 57.51 years (54.2% women) were followed for a median of 6.7 years.

Survival analysis showed that after 5 years, 90.1%of those with a Vit D level > 10 ng/ml were still alive compared to 84.2% of those with levels < 10 ng/ml. In multivariable regression, the hazard ratio (HR) for OS was 2.45 (95% CI 1.28 – 4.68, p = 0.007), i.e., survival was significantly lower among those with lower levels of Vit D. However, when the researchers looked at MSS, the hazard ratio was non-significant (HR = 0.76, 95% CI 0.25 – 2.30, p = 0.629).

The authors suggested that these findings would suggest that vitamin D levels affect overall survival among patients with an invasive melanoma although levels did not appear to have any significant effect on melanoma-specific survival.

At the congress, Lead researcher Dr Inés Gracia-Darder, from the Hospital University Son Espases,Mallorca, Spain, commented that “although previous research has identified that normal levels of vitamin D play a protective role in melanoma survival, this study aimed to further understand this relationship. These findings suggest that vitamin D has a significant impact on people with melanoma, showing in particular that vitamin D deficient patients have a lower overall survival.’

No effect from vitamin D supplementation on acute respiratory infections or COVID-19

13th September 2022

Vitamin D supplementation given to those with a suboptimal status for 6 months had no impact on acute respiratory infections or COVID-19

Vitamin D supplementation (VDS) given to patients identified having suboptimal levels of the vitamin for a period of six months had no effect on the development of all cause acute respiratory infections or COVID-19 according to the findings of a randomised, placebo-controlled trial by a team of UK researchers.

Much has been written on the potential role of vitamin D or VDS as a means of preventing or reducing the adverse sequelae associated with a COVID-19 infection. In fact, regulation of immune function continues to be one of the most well-recognised extra-skeletal actions of vitamin D and there is data indicating that vitamin D up-regulates LL-37, a well-known antimicrobial peptide with antiviral effects and a which provides mechanism through which the vitamin could protect against COVID-19. Moreover, it is already known that vitamin D supplementation is associated with a small, but significant reduction in the risk of acute respiratory infections compared with placebo. During the course of the COVID-19 pandemic, a meta-analysis of observational studies involving nearly 2 million adults, suggested vitamin D deficiency/insufficiency increased susceptibility to COVID-19 and severe COVID-19, although there was a high risk of bias and heterogeneity in studies

However, there is a lack of randomised, controlled trials of VDS in COVID-19 apart from one small, double-blind, placebo-controlled trial of vitamin D supplementation in healthcare workers which found a 77% lower risk of becoming infected among those who received the supplement. For the present study, researchers used a test and treat approach to correct suboptimal vitamin D levels and to then determine the effect on the risk of all cause acute respiratory tract infections and COVID-19. Individuals were recruited from the COVIDENCE UK research study and offered a finger prick test to determine vitamin D status. Participants were then randomised into two groups if their blood 25-hydroxyvitamin D levels were < 75 nmol/L; a low group (800 IU/day) or a high group (3200 IU/day), for 6 month course of vitamin D supplementation. A third group, designated ‘no offer’ served as the placebo arm, i.e., those from the COVIDENCE trial who did not get supplementation and individuals were then randomised 2:1:1 (no offer, low dose, high dose). During the 6-month follow-up, participants were emailed every month with questionnaires to capture incident swab test positive or doctor diagnosed acute respiratory tract infections (including COVID-19) and details of any hospital admission, ventilatory support within hospital and prescriptions for antibiotics. The primary outcome was the proportion of participants who had at least one swab test confirmed or doctor confirmed acute respiratory tract infection. The secondary outcome was the proportion developing a PCR confirmed COVID-19 infection although subgroup analysis was performed examining the impact on hospitalisation and mortality.

Vitamin D supplementation and COVID-19 infection

A total of 6,200 participants with a median age of 60.2 years (67% female) were included and randomised to ‘no offer’ (3,100) or 800 IU/day (1550) with the remainder receiving the higher dose. By the end of the trial (June 2021), 89.1% of participants had one or more doses of a COVID-19 vaccine although at the start, only 0.4% of participants were fully vaccinated.

Overall, 299 participants experienced the primary end point, i.e., at least one test swab confirmed or doctor confirmed acute respiratory tract infection. Compared to the ‘no offer’ group, there was no statistically significant difference for the low dose group (Odds ratio, OR = 1.26, 95% CI 0.96 – 1.66 , p = 0.10) or for the higher dose group (OR = 1.09, 95% CI 0.82 – 1.46, p = 0.55).

For the secondary outcome of COVID-19 infection, there were also no significant differences for a swab confirmed test between the ‘no offer’ and low dose group (OR = 1.39, 95% CI 0.98 – 1.97, p = 0.07) or for the higher dose group (OR = 1.13, 95% CI 0.78 – 1.63, p = 0.53). Similarly, there were no significant differences for admission to hospital, in-hospital use of ventilatory support or death.

The authors concluded that while vitamin D supplementation led to increases in serum 25-hydroxyvitamin D levels, this was not associated with protection against all cause acute respiratory tract infections or COVID-19.

Citation
Jollife DA et al. Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT) BMJ 2022

Severe vitamin D deficiency associated with higher sepsis mortality and longer hospital stay

22nd July 2022

Severe vitamin D deficiency at emergency department admission for severe sepsis is linked to a higher mortality and longer hospital stay

Patients with severe vitamin D deficiency upon admission to an emergency department (ED) with severe sepsis have a higher level of mortality and a longer hospital stay according to the findings of a single centre, prospective study by researchers from Belgium and Italy.

Alterations in the levels of vitamin D have been associated with a higher susceptibility to immune-mediated disorders and inflammatory diseases. However, whilst research suggests that vitamin D has a potential role in the optimal functioning of the immune system, whether correction of vitamin D depletion, particularly among critical care patients, serves an important adjunctive role in either the prevention or treatment of infection is uncertain. In fact, if anything, the available evidence would indicate that vitamin D administration does not improve clinical outcomes among critically ill patients. Nevertheless, an important consideration is how vitamin D levels were normally measured once a patient had been admitted to hospital or after the provision of various treatments and this could have affected measured levels of the vitamin. As a result, in the present study, the researchers sought to determine whether severe vitamin D upon admission to an ED in those with severe sepsis was associated with a higher risk of mortality and a longer hospital stay.

The research team recruited adult patients admitted to the ED with a suspicion of severe sepsis and measured vitamin D levels alongside routine blood samples. Using the patient’s medical records, the team also collected demographic and clinical factors such as the age-adjusted Charleson Comorbidity Index (ACCI), Acute Physiological and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Severe vitamin D deficiency was defined as a level < 12 ng/ml and moderate severity as between 12 and 20 ng/ml. The primary outcome was set at 90-day all-cause mortality and for the secondary outcomes, the team selected a number of measures including the length of hospital stay.

Severe vitamin D levels and mortality

A total of 164 patients with a median age of 66.7 years (35% female) were included in the final analysis. Among the cohort, 46.3% of patients had vitamin D levels below 12 ng/ml and 121 of the cohort were admitted to intensive care. The 90-day all-cause mortality occurred in 26.4% of the entire cohort and the median hospital length of stay was 14 days.

Among those with vitamin D levels below 12 ng/ml, 32.9% of patients died compared to 20.5% in the non-severe deficiency group (p = 0.07) and in multivariable analysis after adjustment for sepsis severity and co-morbidities, this was found to be independently associated with 90-day mortality (odds ratio, OR = 2.69, 95% CI 1.03 – 7, p = 0.043). Using Cox analysis again adjusted for confounders, severe vitamin D deficiency was also associated with a lower chance of hospital discharge (hazard ratio, HR = 0.66, 95% CI 0.44 – 0.98, p = 0.043).

As with the overall cohort, among patients admitted to ICU, those with severe vitamin D deficiency had a higher risk of 90-day mortality (HR = 3.06, 95% CI 1.05 – 8.94, p = 0.04) and a lower chance of discharge (HR = 0.51).

Citation
Malinverni S et al. Severe vitamin D deficiency in patients admitted to the emergency department with severe sepsis is associated with an increased 90-day mortality Emerg Med J 2022

Study finds vitamin D status and COVID-19 diagnosis shows inconsistent associations

14th June 2022

A large study revealed no consistent associations between vitamin D status and COVID-19 outcomes such as infection, hospitalisation and death

There are inconsistent associations between vitamin D status and the diagnosis of COVID-19, hospitalisations and mortality according to the findings of a large cohort study by researchers from Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Vitamin D is essential for bone health such that prolonged and severe vitamin D deficiency gives rise to rickets in children and osteomalacia in adults. Furthermore, vitamin D is an immune system modulator that induces an increase in antimicrobial proteins and activity against pathogens. In a systemic review of studies, it was found that supplementation with vitamin D results in a small reduction in the risk of acute respiratory infections although the role of vitamin D in COVID-19 remains uncertain. In a 2021 Cochrane review, the authors concluded that there is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. But if vitamin D status and in particular, a deficiency of the vitamin, is associated with COVID-19, the use of supplements could be a valuable health intervention. As a result, for the present study, the UK team set out to examine the association between vitamin D status and several COVID-19 outcomes including infection, hospitalisation and death. They used data held within the UK Biobank and included individuals for whom at least one serum vitamin D test was available. Levels were recorded as deficient (< 25 nmol/L), insufficient (25 – 49 nmol/L) and sufficient ( > 50 nmol/L) and the primary outcome of interest was a laboratory confirmed infection with COVID-19. For their secondary outcomes, the team examined hospitalisation and mortality due to infection with the virus. The team also considered the risk of being diagnosed with COVID-19 when the vitamin D status was assessed, i.e., during the summer and winter months and used the definition of vitamin D sufficiency as the reference point. The analysis was performed using logistic regression after adjustment for covariates which included demographics, body mass index, smoking status and ethnicity.

Vitamin D status and COVID-19 outcomes

A total of 307, 512 individuals were included in the analysis of whom, 46% were deemed to vitamin D sufficient, 41% insufficient and 12% deficient. A total of 10,165 people became infected with COVID-19 with 51.4% of infections reported during autumn, 31% in the winter and only 3.8% in the summer.

Interestingly, during the summer months, participants who were vitamin D deficient had a 14% lower risk of being diagnosed with COVID-19 compared to those who were vitamin D sufficient (Hazard ratio, HR = 0.86, 95% CI 0.77 – 0.95, p < 0.01). In contrast, during the non-summertime months, the risk of becoming infected with COVID-19 was 14% higher among those who were vitamin D deficient (HR = 1.14, 95% CI 1.01 – 1.30, p = 0.04). However, there were no significant associations for individuals deemed vitamin D insufficient irrespective of the time of year.

With respect to COVID-19-related hospitalisations, compared to those who were vitamin D sufficient, there was no evidence that any other vitamin D status significantly affected the risk. Similarly, there was no evidence that the risk of COVID-19 mortality was affected by vitamin D levels.

In their conclusion the authors reported that there were inconsistent associations between vitamin D status and a diagnosis of COVID-19 and no clear association between vitamin D levels and either hospitalisation or death.

Citation
Lin LY et al. The association between vitamin D status and COVID-19 in England: A cohort study using UK Biobank PLoS One 2022

Combination of exercise, omega-3 fatty acids and vitamin D reduces cancer risk in the elderly

13th May 2022

A randomised trial has found that a combination of exercise, omega-3 fatty acids and vitamin D significantly reduces cancer risk in patients over 70

Cancer is the second leading cause of death globally and in 2018, it accounted for approximately 9.6 million deaths. Although cancer can strike at any age, many types of cancer become more prevalent with increasing age. However, recent research has found that for most adults, cancer does not have to be an inevitable consequence of growing older. In fact, adoption of healthy lifestyle measures based on a combination of exercise, diet, smoking status, alcohol consumption, and anthropometry, in other words, simple behavioural modifications, have been shown to produce a sizeable reduction in the risk of some cancers. Among healthy interventions, there is evidence that physical activity is associated with a lower risk of several cancers. Equally, use of vitamin D supplements has some evidence to support its use in reducing the incidence of advanced (metastatic or fatal) cancer. Finally, an omega-3 fatty acid-rich diet, can significantly delay mouse tumour growth when compared with a monounsaturated fatty acid-rich diet. Nevertheless, whether a combination of exercise, vitamin D and omega-3 fatty acids provides a synergistic and preventative effect against cancer is less clear.

For the present study, the researchers undertook a randomised controlled trial, which sought to examine the combination of exercise, supplementation with vitamin D and omega-3 fatty acids in older adults and how this impacted on the subsequent development of cancer. Their DO-HEALTH trial examined the combined effect of simple home strength exercise (SHEP), vitamin D (2000 IU/day) and/or 1g/day of marine omega-3 fatty acids, in healthy adults 70 years of age and older. For the primary outcome, the team considered the time to the development of a verified invasive cancer.

Combination of exercise, omega-3 fatty acids, vitamin D and cancer development

A total of 2157 individuals with a mean age of 74.9 years (61.7% female) were included in the study and followed for a median of 2.99 years. During this period of time there were 81 invasive cancers diagnosed and verified.

For the three separate interventions, the adjusted hazard ratios (compared to controls) were 0.76 (95% CI 0.49 – 1.18) for vitamin D, 0.70 (95% CI 0.44 – 1.09) for omega-3 fatty acids and 0.74 (95% CI 0.48 – 1.15) for SHEP). In other words, while there were beneficial effects from the individual interventions, the effects were not statistically significant, but when two of the interventions were combined, the effect did become statistically significant. For instance, the combination of SHEP and omega-3 resulted in an adjusted hazard ratio of 0.52 (95% CI 0.28 – 0.97, p = 0.039). However, the greatest benefit was derived from the combination of exercise, vitamin D and omega-3 fatty acids, with an adjusted hazard ratio of 0.39 (95% CI 0.18 – 0.85, p = 0.017).

The authors calculated that the number needed to treat to prevent one incident case of cancer after three years with the three treatments combined was 35.

They concluded that future studies should focus on the benefit of combining interventions as a means of cancer prevention.

Citation
Bischoff-Ferrari HA et al. Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial Am J Clin Nutr 2022

Oral bolus of vitamin D at admission failed to improve overall COVID-19 outcomes

4th March 2022

An oral bolus of 100,000 IU of vitamin D given to patients with COVID-19 upon admission to hospital was of no overall benefit

The use of a large oral bolus of cholecalciferol (vitamin D) given to patients with moderate-to-severe COVID-19 upon admission to a hospital failed to improve overall outcomes compared with no treatment. This was the conclusion of a large, randomised trial by researchers from the Hospital Universitario Central de Asturias (HUCA), Avda. Roma, Spain. However, in a separate subgroup analysis, it did appear that there were positive benefits among those with higher baseline calcidiol levels upon admission.

An inverse relationship has been established between vitamin D levels and the development of several autoimmune diseases although whether this effect on the immune system has a positive impact upon the body’s ability to fight respiratory infections and on chronic diseases is currently uncertain. Much has been written on the potential benefits of vitamin D among patients with COVID-19 and one systematic review concluded that low vitamin D levels represent an increased risk of acute respiratory distress syndrome, admission to an intensive care unit or mortality due to COVID-19 infection. Nevertheless, a limitation from the aforementioned systematic review, it how the data were derived from observational studies and there has been a distinct absence of randomised, controlled trials, which can provide more robust evidence.

For the present study, the Spanish team undertook a randomised trial (COVID-VIT-D) to investigate whether a single, large, oral bolus of 100,000 IU of cholecalciferol given upon admission to hospital, could impact on the outcomes associated with a COVID-19 infection. Eligible patients (18 years and over) were those hospitalised for moderate-to-severe COVID-19 infection and who were randomised 1:1, to receive a single oral bolus of cholecalciferol or nothing. Patients were followed from admission until discharge and demographic, co-morbidity, biochemical, imaging results and all treatments used were recorded. The three primary outcomes for the trial were: length of hospitalisation; admission to an intensive care unit (ICU) and mortality. In a separate cohort analysis, the researchers examined the relationship between serum calcidiol upon admission with pulmonary involvement and the same three primary outcomes of the trial.

Single oral bolus and COVID-19 outcomes

A total of 543 patients with a median age of 58 years (65% male) were randomised to vitamin D (274) or nothing. The most frequent co-morbidities were hypertension (43.8%), diabetes (24.7%) and cardiovascular disease (21.2%). In addition, pulmonary involvement was diagnosed in 83.1% of those upon admission.

With respect to the primary outcomes, there were no differences between the two groups. The median length of hospital stay was 10 vs 9.5 days (vitamin D vs control), admission to ICU (172.% vs 16.4%) and mortality (8% vs 5.6%).

When considering the lowest (< 10ng/ml) and highest(> 25 ng/ml) baseline levels, the presence of a higher calcidiol level was associated with a lower risk of pulmonary involvement upon admission (odds ratio, OR = 0.21, 95% CI 0.08 – 0.60) and a lower risk of ICU admission (hazard ratio, HR = 0.35, 95% CI 0.13 – 0.95). However, baseline calcidiol levels had no effect on the length of hospitalisation or mortality.

The authors concluded that while a single oral bolus of vitamin D did not improve overall outcomes for those hospitalised with COVID-19, higher baseline calcidiol levels did appear to have better outcomes.

Citation
Cannata‐Andía JB et al. A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D—a randomised multicentre international clinical trial BMC Med 20222


Vitamin D-deficient patients 14-times more likely to get severe COVID-19

7th February 2022

Vitamin D-deficient patients are more likely to get severe COVID-19 and die compared with those with sufficient levels of the vitamin

Vitamin D-deficient individuals have been shown to be much more likely to experience severe COVID-19 and die in comparison to those with normal or sufficient levels of the vitamin. This was an important finding by researchers from the Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, Israel.

Previous research has shown how vitamin D has a protective effect against respiratory tract infections when taken as a once daily dosage. Moreover, a 2021 systematic review which included 46 randomised controlled trials with 48,488 individuals, re-affirmed the benefits of daily supplementation with 400 –1000 IU of vitamin D for reducing the risk of acute respiratory tract infections compared with placebo. Several studies undertaken during the COVID-19 pandemic have suggested that a vitamin D deficient status was associated with increased COVID-19 risk. Furthermore, other data has shown how the vitamin D level is markedly low in severe COVID-19 patients although this was measured once in hospital. However, what is less clear, is the extent to which pre-infection or baseline vitamin D levels, impact on the clinical outcomes once patients become infected with COVID-19.

For the present study, the Israeli team set out to determine whether COVID-19 disease severity correlated with patient’s most recent vitamin D levels as documented in their medical records. They undertook a retrospective study of hospitalised, adult patients with a PCR-confirmed COVID-19 infection. The team defined COVID-19 disease severity at the point of highest severity. For instance, if a patient was admitted with mild disease and which subsequently deteriorated, this would be categorised as a critical illness. They used the most recent medical record for vitamin D status and then categorised patients as vitamin D deficient (< 20 ng/ml), insufficient (20 – 29.9 ng/ml), adequate (30 – 39.9 ng/ml) and high-normal (40 ng/ml). They used multivariable analysis to examine the relationship between vitamin D status and COVID-19 disease severity.

Vitamin D deficient status and COVID-19 severity

A total of 253 individuals with a mean age of 63.3 years (56.9% female) were included in the analysis. Among the cohort, 52.5% were vitamin D-deficient, 14.2% had levels between 20 and 30ng/ml and 15.8% had a level of 40ng/ml or above.

Mortality from COVID-19 occurred in 2.3% of those with adequate vitamin D levels and 25.6% of individuals who were vitamin D deficient (p < 0.001). When stratifying COVID-19 disease severity with vitamin D status, among those with the lowest vitamin D levels, a higher proportion (87.4%) developed severe or critical COVID-19 compared to mild to moderate disease, 34.3% (p < 0.001). In regression analysis, patients with vitamin D deficiency compared to those with high-normal levels (40 ng/ml) were 14 times more likely to develop severe or critical illness (odds ratio, OR = 14, 95% CI 4 – 51, p < 0.001). Overall, when comparing pre-hospital vitamin D levels with COVID-19 disease severity, there was a clear inverse relationship such that as vitamin D levels reduced, COVID-19 disease severity increased.

Further analysis revealed that age was an independent risk factor for more severe disease and the strongest correlation between vitamin D status and COVID-19 severity occurred in those aged 50 years and over (r = – 0.74, p < 0.001). However, this correlation was still significant among those under 50 years of age (r = -0.66, p < 0.001).

The authors described how early on in the current pandemic, there was much debate on the role of vitamin D in protecting against COVID-19. They suggested that their study provided further evidence of how vitamin D deficient patients were at a much higher risk of more severe COVID-19 infection and called for further studies to investigate if and when vitamin D supplementing in those who are deficient, impacts on COVID-19-related outcomes.

Citation
Dror AA et al. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness PloS One 2022