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Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.
Sabico, S, Enani, MA, Sheshah, E, Aljohani, NJ, Aldisi, DA, Alotaibi, NH, Alshingetti, N, Alomar, SY, Alnaami, AM, Amer, OE, et al
Nutrients. 2021;13(7)
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A highly contagious virus called SARS-CoV-2 is responsible for the Covid-19 pandemic. Vitamin D adjuvant therapy has been identified as a promising strategy for reducing the severity of Covid-19 outcomes in the elderly. Also, a low Vitamin D status significantly correlates with Covid-19 severity. This multi-centre randomised, open-label clinical trial evaluated the beneficial effects of 5000 IU versus 1000 IU Vitamin D3 daily supplementation for two weeks on recovery of symptoms in patients with mild-to-moderate Covid-19 and suboptimal Vitamin D status. Thirty-six Covid-19 patients received 5000 IU Vitamin D3 daily, and thirty-three Covid-19 patients received 1000 IU Vitamin D3 daily. The 5000 IU Vitamin D3 group was significantly younger and had a significantly lower BMI than the 1000 IU Vitamin D3 group. The 5000 IU Vitamin D3 group showed significant improvements in the severity of the Covid-19 symptoms compared to the 1000 IU Vitamin D3 group. Further robust studies are needed to evaluate the effects of Vitamin D3 supplementation in patients with high BMI, severe Covid-19 symptoms, and prevention of Covid-19. Healthcare professionals can use the results of this study to understand the effects of different doses of Vitamin D3 supplements in patients with mild-to-moderate Covid-19 symptoms and suboptimal Vitamin D status.
Abstract
OBJECTIVE Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.
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Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS-CoV-2 Infection.
Townsend, L, Dyer, AH, McCluskey, P, O'Brien, K, Dowds, J, Laird, E, Bannan, C, Bourke, NM, Ní Cheallaigh, C, Byrne, DG, et al
Nutrients. 2021;13(7)
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Persistence of symptoms following COVID-19 infection is known as long COVID and occurs in up to a third of sufferers and can last for as long as 6 months post infection. Tiredness and reduced capacity to exercise are characteristic of long COVID, however why these symptoms persist in a handful of patients is unknown. Vitamin D deficiency is gaining attention for its potential to improve symptoms of tiredness, however there are few studies examining its relationship with long COVID. This observational study of 149 patients who had been diagnosed with COVID-19 aimed to determine the relationship between symptoms of long COVID, inflammation in the body and vitamin D levels. The results showed that fatigue was common, but there was no association between vitamin D levels and fatigue, inflammation, or capacity to exercise. Interestingly women were more likely to experience fatigue in this study. It was concluded that fatigue and reduced exercise capacity are independent of vitamin D in those who have had COVID-19. This study could be used by healthcare professionals to understand symptoms of long COVID, and that vitamin D may not be effective for those symptoms.
Abstract
The emergence of persistent symptoms following SARS-CoV-2 infection, known as long COVID, is providing a new challenge to healthcare systems. The cardinal features are fatigue and reduced exercise tolerance. Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity. We hypothesize that vitamin D levels are associated with persistent symptoms following COVID-19. Herein, we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance, assessed by the Chalder Fatigue Score, six-minute walk test and modified Borg scale. Multivariable linear and logistic regression models were used to evaluate the relationships. A total of 149 patients were recruited at a median of 79 days after COVID-19 illness. The median vitamin D level was 62 nmol/L, with n = 36 (24%) having levels 30-49 nmol/L and n = 14 (9%) with levels <30 nmol/L. Fatigue was common, with n = 86 (58%) meeting the case definition. The median Borg score was 3, while the median distance covered for the walk test was 450 m. No relationship between vitamin D and the measures of ongoing ill-health assessed in the study was found following multivariable regression analysis. These results suggest that persistent fatigue and reduced exercise tolerance following COVID-19 are independent of vitamin D.
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Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.
Holman, N, Knighton, P, Kar, P, O'Keefe, J, Curley, M, Weaver, A, Barron, E, Bakhai, C, Khunti, K, Wareham, NJ, et al
The lancet. Diabetes & endocrinology. 2020;8(10):823-833
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Diabetes, cardiovascular disease, and hypertension are the most common chronic conditions predisposing people to severe COVID-19 disease. The aim of this population-based cohort study, using data from 98% of general practices in England, was to investigate the associations between various risk factors, including poor blood sugar control, and COVID-19-related deaths in people with type 1 and type 2 diabetes. Between Feb 16 and May 11, 2020, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes, of which almost 30% had COVID-19 listed on the death certificate, either a primary underlying or secondary cause of death. Male gender, age and being of Black or Asian ethnicity were associated with an increased mortality from COVID-19. Poor blood sugar control, as determined by HbA1C, prior to infection was strongly associated with COVID-19-related death, independent of other risk factors. Obesity (BMI of 30 or over) as well as being underweight were also significantly associated with COVID-19 mortality. The authors discuss that people with diabetes are at increased risk of many serious infections and that high blood glucose levels are known to impair immunity and may amplify the hyperimmune response associated with severe COVID-19.
Abstract
BACKGROUND Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. METHODS We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. FINDINGS Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017-19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48-53 mmol/mol (6·5-7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50-3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47-1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48-53 mmol/mol (HR 1·22 [95% CI 1·15-1·30, p<0·0001] for 59-74 mmol/mol [7·6-8·9%] and 1·36 [1·24-1·50, p<0·0001] for 75-85 mmol/mol [9·0-9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001). INTERPRETATION Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. FUNDING None.
4.
Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?
Li, L, Spranger, L, Soll, D, Beer, F, Brachs, M, Spranger, J, Mai, K
Metabolism: clinical and experimental. 2020;113:154401
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Obesity is now recognised as a risk factor for increased severity of Covid-19 infections. ACE-2 is a protein that has many functions but also allows Covid-19 into cells and is particularly evident in body tissues, which store fat. It is therefore possible that Covid-19 will target fat-storing tissues in the body. This 12-month randomised control weight-loss intervention study of 143 obese individuals aimed to determine ACE-2 expression and whether it could be modified by weight loss. The results showed that ACE-2 was only present in fat storing tissue and not muscle tissue. Interestingly individuals with pre-diabetes or diabetes had the lowest levels of ACE-2. Weight loss resulted in reduced ACE-2 in fat storing tissue, which resulted in an improvement in markers for diabetes. It was concluded that reduction of ACE-2 in fat storing tissues as a result of weight loss can improve markers for diabetes and could impact the severity of Covid-19 infection. Healthcare professionals could use this study to understand how weight loss in patients with obesity could decrease their risk of severe Covid-19 infection.
Abstract
BACKGROUND & AIMS Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.