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Overweight and obesity as risk factors for COVID-19-associated hospitalisations and death: systematic review and meta-analysis.
Sawadogo, W, Tsegaye, M, Gizaw, A, Adera, T
BMJ nutrition, prevention & health. 2022;5(1):10-18
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A novel coronavirus named SARS-CoV-2, causing COVID-19, emerged in late 2019. The prognosis of COVID-19 has been consistently reported to worsen with older age, male sex and comorbidities. The aim of this study was to quantify the association between overweight or obesity and COVID-19-related hospitalisations and death, and to assess the magnitude of the association and the potential dose–response relationships. This study is a systematic review and meta-analysis of 208 studies. A total of 3 550 977 participants from over 32 countries were included in this study. Results indicate that being overweight increases the risk of COVID-19-related hospitalisations but not death while obesity and extreme obesity increase the risk of both COVID-19-related hospitalisations and death. In addition, there was a linear dose–response association between obesity categories and COVID-19 outcomes. However, the strength of the association has weakened over time following the pattern of the first wave of COVID-19. Authors conclude that their findings suggest the importance of increased vigilance towards people with excess adiposity. Some preventative measures for this vulnerable group include prompt access to COVID-19 testing and healthcare, as well as prioritisation for COVID-19 vaccination.
Abstract
Objective: To quantify the current weight of evidence of the association between overweight and obesity as risk factors for COVID-19-related hospitalisations (including hospital admission, intensive care unit admission, invasive mechanical ventilation) and death, and to assess the magnitude of the association and the potential dose-response relationships. Design: PubMed, Embase, Cochrane, Web of Sciences, WHO COVID-19 database and Google Scholar were used to identify articles published up to 20 July 2021. Peer-reviewed studies reporting adjusted estimates of the association between overweight or obesity and COVID-19 outcomes were included. Three authors reviewed the articles and agreed. The quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis was used to estimate the combined effects. Results: A total of 208 studies with 3 550 997 participants from over 32 countries were included in this meta-analysis. Being overweight was associated with an increased risk of COVID-19-related hospitalisations (OR 1.19, 95% CI 1.12 to 1.28, n=21 studies), but not death (OR 1.02, 95% CI 0.92 to 1.13, n=21). However, patients with obesity were at increased risk of both COVID-19-related hospitalisations (OR 1.72, 95% CI 1.62 to 1.84, n=58) and death (OR 1.25, 95% CI 1.19 to 1.32, n=77). Similarly, patients with extreme obesity were at increased risk of COVID-19-related hospitalisations (OR 2.53, 95% CI 1.67 to 3.84, n=12) and death (OR 2.06, 95% CI 1.76 to 3.00, n=19). There was a linear dose-response relationship between these obesity categories and COVID-19 outcomes, but the strength of the association has decreased over time. Conclusion: Being overweight increases the risk of COVID-19-related hospitalisations but not death, while obesity and extreme obesity increase the risk of both COVID-19-related hospitalisations and death. These findings suggest that prompt access to COVID-19 care, prioritisation for COVID-19 vaccination and other preventive measures are warranted for this vulnerable group.
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Lifestyle risk behaviours among adolescents: a two-year longitudinal study of the impact of the COVID-19 pandemic.
Gardner, LA, Debenham, J, Newton, NC, Chapman, C, Wylie, FE, Osman, B, Teesson, M, Champion, KE
BMJ open. 2022;12(6):e060309
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The global spread of COVID-19 and subsequent lockdown measures have presented challenges worldwide. Previous research has highlighted the importance of six key lifestyle behaviours, including diet, physical activity, sleep, sedentary behaviour (including recreational screen time), alcohol use and smoking—collectively referred to as the ‘Big 6’—for the short-term and long-term health of adolescents. The aim of this study was to examine changes in the prevalence of six key chronic disease risk factors from before to during the COVID-19 pandemic, and also to explore whether differences over time are associated with gender and lockdown status. This study is a prospective cohort study among a large and geographically diverse sample of adolescents. The sample included 983 students (girls = 54.8%) from 22 schools. Results show that: - over the 2-year period, the prevalence of excessive recreational screen time, insufficient fruit intake and alcohol and tobacco use increased. - alcohol use increased more among girls compared to boys. - the prevalence of insufficient sleep reduced in the overall sample; yet, increased among girls. - being in lockdown was associated with improvements in sugar-sweetened beverages consumption and discretionary food intake. Authors conclude that supporting young people to improve or maintain their health behaviours, regardless of the course of the pandemic, is important, alongside targeted research and intervention efforts to support groups that may be disproportionately impacted, such as adolescent girls.
Abstract
OBJECTIVE To examine changes in the prevalence of six key chronic disease risk factors (the "Big 6"), from before (2019) to during (2021) the COVID-19 pandemic, among a large and geographically diverse sample of adolescents, and whether differences over time are associated with lockdown status and gender. DESIGN Prospective cohort study. SETTING Three Australian states (New South Wales, Queensland and Western Australia) spanning over 3000 km. PARTICIPANTS 983 adolescents (baseline Mage=12.6, SD=0.5, 54.8% girl) drawn from the control group of the Health4Life Study. PRIMARY OUTCOMES The prevalence of physical inactivity, poor diet (insufficient fruit and vegetable intake, high sugar-sweetened beverage intake, high discretionary food intake), poor sleep, excessive recreational screen time, alcohol use and tobacco use. RESULTS The prevalence of excessive recreational screen time (prevalence ratios (PR)=1.06, 95% CI=1.03 to 1.11), insufficient fruit intake (PR=1.50, 95% CI=1.26 to 1.79), and alcohol (PR=4.34, 95% CI=2.82 to 6.67) and tobacco use (PR=4.05 95% CI=1.86 to 8.84) increased over the 2-year period, with alcohol use increasing more among girls (PR=2.34, 95% CI=1.19 to 4.62). The prevalence of insufficient sleep declined across the full sample (PR=0.74, 95% CI=0.68 to 0.81); however, increased among girls (PR=1.24, 95% CI=1.10 to 1.41). The prevalence of high sugar-sweetened beverage (PR=0.61, 95% CI=0.64 to 0.83) and discretionary food consumption (PR=0.73, 95% CI=0.64 to 0.83) reduced among those subjected to stay-at-home orders, compared with those not in lockdown. CONCLUSION Lifestyle risk behaviours, particularly excessive recreational screen time, poor diet, physical inactivity and poor sleep, are prevalent among adolescents. Young people must be supported to find ways to improve or maintain their health, regardless of the course of the pandemic. Targeted approaches to support groups that may be disproportionately impacted, such as adolescent girls, are needed. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12619000431123).
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A Systematic Review of the Impact of the First Year of COVID-19 on Obesity Risk Factors: A Pandemic Fueling a Pandemic?
Daniels, NF, Burrin, C, Chan, T, Fusco, F
Current developments in nutrition. 2022;6(4):nzac011
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Coronavirus disease 2019 (COVID-19) is one of the most serious infectious disease outbreaks in recent history. Among the factors that can increase the risk of obesity, some seem to play a more prominent role than others such as depression, emotional eating, sedentary lifestyle and the socioeconomic status. The aim of this study was to explore the indirect effects of the first year of COVID-19 on obesity and its risk factors. This study is a systematic review of 87 studies with over 350,000 participants. Results show that: - overall, there was a general trend of weight gain during the pandemic. - there were differences in dietary changes, with some studies showing an improvement in diet. - some beneficial effects were observed in the dieting domain, such as higher consumption of home-cooked meals and healthy food (e.g., vegetables). However, there was an increasing trend in the overall food and alcohol consumption. - financial hardship and job loss were unavoidable consequences of the pandemic lockdown. However, although the impact of the countermeasures used to curb the COVID-19 pandemic was evident on obesity risk factors, none of the studies included in the research explored the direct impact of the risk factors on obesity itself. Authors conclude by pointing out the need for future research that aims at strengthening the link between stressful circumstances and a rise in risk factors for obesity and weight gain.
Abstract
Obesity is increasingly prevalent worldwide. Associated risk factors, including depression, socioeconomic stress, poor diet, and lack of physical activity, have all been impacted by the coronavirus disease 2019 (COVID-19) pandemic. This systematic review aims to explore the indirect effects of the first year of COVID-19 on obesity and its risk factors. A literature search of PubMed and EMBASE was performed from 1 January 2020 to 31 December 2020 to identify relevant studies pertaining to the first year of the COVID-19 pandemic (PROSPERO; CRD42020219433). All English-language studies on weight change and key obesity risk factors (psychosocial and socioeconomic health) during the COVID-19 pandemic were considered for inclusion. Of 805 full-text articles that were reviewed, 87 were included for analysis. The included studies observed increased food and alcohol consumption, increased sedentary time, worsening depressive symptoms, and increased financial stress. Overall, these results suggest that COVID-19 has exacerbated the current risk factors for obesity and is likely to worsen obesity rates in the near future. Future studies, and policy makers, will need to carefully consider their interdependency to develop effective interventions able to mitigate the obesity pandemic.
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Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.
Dissanayake, HA, de Silva, NL, Sumanatilleke, M, de Silva, SDN, Gamage, KKK, Dematapitiya, C, Kuruppu, DC, Ranasinghe, P, Pathmanathan, S, Katulanda, P
The Journal of clinical endocrinology and metabolism. 2022;107(5):1484-1502
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Vitamin D is implicated in optimum function of the immune system. Its deficiency has been linked to susceptibility to respiratory infections. It is postulated that vitamin D deficiency/insufficiency is also associated with COVID-19. The aim of this study was to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. This study is a systematic review and meta-analysis of seventy-six publications. Results show increased odds of developing COVID-19, progression to severe COVID-19 and death in people with vitamin D deficiency/insufficiency. In fact, people who developed COVID-19, severe COVID-19 and fatal disease had lower 25-hydroxy vitamin D concentration compared to people without COVID-19 or non-severe COVID-19 or non-fatal COVID-19 respectively. Authors conclude that Vitamin D deficiency/insufficiency may increase the risk of developing COVID-19 infection and susceptibility to more severe disease.
Abstract
PURPOSE Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.
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Effects of Vitamin D Serum Level on Morbidity and Mortality in Patients with COVID-19: A Systematic Review and Meta-Analysis.
Hu, Y, Kung, J, Cave, A, Banh, HL
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 2022;25:84-92
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COVID-19 caused by SARS-CoV-2 infection is associated with severe acute respiratory syndrome resulting from the excessive inflammatory response at 5-7 days. It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. The aim of this study was to determine the clinical effects of Vitamin D serum concentration in COVID-19 patients. This study is a systematic review and meta-analysis of 20 studies. Results show that Vitamin D serum concentration was not statistically associated with mortality and ICU admission, ventilator support requirement, and length of hospital stay. Authors conclude that additional randomized controlled trials are required to provide a specific supplemental vitamin dose and Vitamin D serum concentration.
Abstract
PURPOSE It has been shown that low Vitamin D serum concentration is associated with increased pneumonia and viral respiratory infections. Vitamin D is readily available, inexpensive, and easy to administer to subjects infected with COVID-19. If effective in reducing the severity of COVID-19, it could be an important and feasible therapeutic intervention. METHODS We performed a systematic review and meta-analysis of the literature to determine the effects of Vitamin D serum concentration on mortality and morbidity in COVID-19 patients. The primary objectives were to determine if Vitamin D serum concentration decrease mortality, ICU admissions, ventilator support, and length of hospital stay in COVID-19 patients. RESULTS A total of 3572 publications were identified. Ultimately, 20 studies are included. A total of 12,806 patients aged between 42 to 81 years old were analyzed. The pooled estimated RR for mortality, ICU admission, ventilator support and length of hospital stay were 1.49 (95% CI: 1.34, 1.65), 0.87 (95% CI: 0.67, 1.14), 1.29 (95% CI: 0.79, 1.84), and 0.84 (95% CI -0.45, 2.13). CONCLUSION There is no statistical difference in mortality, ICU admission rate, ventilator support requirement, and length of hospital stay in COVID-19 patients with low and high Vitamin D serum concentration.
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Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review.
Chen, M, Qin, R, Jiang, M, Yang, Z, Wen, W, Li, J
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;104:415-422
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The rapidly spreading nature of COVID-19 has put an emphasis on the importance of fast diagnosis. Gold standard diagnosis is through reverse transcription polymerase chain reaction (RT-PCR) tests, which aims to detect the presence of COVID-19. However, challenges with collection techniques and when in the disease lifecycle these tests are taken, can affect their reliability, highlighting a need for alternative methods of testing. Other testing methods exist, which involve testing the body’s own immune response to the presence of COVID-19, however these may also have their limitations. This systematic review and meta-analysis aimed to determine the effectiveness of testing the body’s own immune reaction for the presence of COVID-19. The results showed that testing the body’s immune reaction was effective, however if the person being tested is at an early stage in the disease, then it may be misdiagnosed. This study could be used by healthcare professionals to understand that the use of any type of COVID-19 testing may have its limitations, and although a person may test negative, there is still a possibility that they have the infection if symptoms exist
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.
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Online-Delivered Group and Personal Exercise Programs to Support Low Active Older Adults' Mental Health During the COVID-19 Pandemic: Randomized Controlled Trial.
Beauchamp, MR, Hulteen, RM, Ruissen, GR, Liu, Y, Rhodes, RE, Wierts, CM, Waldhauser, KJ, Harden, SH, Puterman, E
Journal of medical Internet research. 2021;23(7):e30709
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A widely scalable, nonpharmacological, and cost-effective approach promoted by the World Health Organization to support mental health during the pandemic corresponds to regular physical activity. The aim of this study was to assess whether a group-based online exercise programme or a personal online exercise programme compared to a waitlist control can improve the psychological health of previously low active older adults during the early stages of the COVID-19 pandemic. The study is a prospective, 3-arm, parallel, randomized controlled trial. Two-hundred and forty-one low active older adults, aged between 65 and 69 years, were enrolled in the study. Participants were stratified to ensure equal distribution of men and women across conditions. Results indicate that both physical activity programmes showed improvements in mental health when compared with control participants, which represents a notable outcome for older adults in the current COVID-19 pandemic. Authors conclude that virtually delivered interventions are feasible and, when delivered in a group setting, can aid the retention of previously low active older adults.
Abstract
BACKGROUND In response to the COVID-19 pandemic, experts in mental health science emphasized the importance of developing and evaluating approaches to support and maintain the mental health of older adults. OBJECTIVE The aim of this study was to assess whether a group-based exercise program relative to a personal exercise program (both delivered online) and waitlist control (WLC) can improve the psychological health of previously low active older adults during the early stages of the COVID-19 pandemic. METHODS The Seniors COVID-19 Pandemic and Exercise (SCOPE) trial was a 3-arm, parallel randomized controlled trial conducted between May and September 2020 in which low active older adults (aged ≥65 years) were recruited via media outlets and social media. After baseline assessments, consented participants were randomized to one of two 12-week exercise programs (delivered online by older adult instructors) or a WLC condition. A total of 241 older adults (n=187 women) provided baseline measures (via online questionnaires), were randomized (ngroup=80, npersonal=82, ncontrol=79), and completed measures every 2 weeks for the duration of the trial. The trial's primary outcome was psychological flourishing. Secondary outcomes included global measures of mental and physical health, life satisfaction, and depression symptoms. RESULTS The results of latent growth modeling revealed no intervention effects for flourishing, life satisfaction, or depression symptoms (P>.05 for all). Participants in the group condition displayed improved mental health relative to WLC participants over the first 10 weeks (effect size [ES]=0.288-0.601), and although the week 12 effect (ES=0.375) was in the same direction the difference was not statistically significant (P=.089). Participants in the personal condition displayed improved mental health, when compared with WLC participants, in the same medium ES range (ES=0.293-0.565) over the first 8 weeks, and while the effects were of a similar magnitude at weeks 10 (ES=0.455, P=.069) and 12 (ES=0.258, P=.353), they were not statistically significant. In addition, participants in the group condition displayed improvements in physical health when compared with the WLC (ES=0.079-0.496) across all 12 weeks of the study following baseline. No differences were observed between the personal exercise condition and WLC for physical health (slope P=.271). CONCLUSIONS There were no intervention effects for the trial's primary outcome (ie, psychological flourishing). It is possible that the high levels of psychological flourishing at baseline may have limited the extent to which those indicators could continue to improve further through intervention (ie, potential ceiling effects). However, the intervention effects for mental and physical health point to the potential capacity of low-cost and scalable at-home programs to support the mental and physical health of previously inactive adults in the COVID-19 pandemic. TRIAL REGISTRATION ClinicalTrials.gov NCT04412343; https://clinicaltrials.gov/ct2/show/NCT04412343.
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Eating Behaviour Changes during the COVID-19 Pandemic: A Systematic Review of Longitudinal Studies.
González-Monroy, C, Gómez-Gómez, I, Olarte-Sánchez, CM, Motrico, E
International journal of environmental research and public health. 2021;18(21)
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The appearance of coronavirus disease 2019 (COVID-19), has led not only to changes in relationship patterns but also lifestyle habits. The aim of this study was to evaluate eating behaviour changes during the COVID-19 pandemic by establishing a comparison of eating behaviours before and after the outbreak of the pandemic. This study is a systematic review of 23 longitudinal studies. Results indicate that: - the frequency of meals is not associated with the amount of food eaten. - there was not a correlation between gender and age with specific eating behaviours. Authors conclude that further research focusing not only on food intake but also on alcohol consumption and its consequences is required. This may aid in the development of a progression of ‘eating behaviour during a state of alarm’ and in the establishment of a benchmark for future directions to help improve guidelines for achieving proper nutrition aimed at the new normality.
Abstract
Eating behaviour is a complex construct that is liable to be modified by external factors. Due to the outbreak of coronavirus disease 2019 (COVID-19), many restrictive measures were carried out with the aim of reducing the impact of this disease. As a result, lifestyles were disrupted, which could affect eating behaviours. The aim of this systematic review of longitudinal studies was to assess changes in eating behaviour during the COVID-19 pandemic by establishing a comparison of eating behaviours before and after the outbreak of the pandemic. This study followed the PRISMA guidelines (PROSPERO CRD42020203246), whereas to assess the quality of the studies, the Newcastle-Ottawa Quality Assessment Scale (NOS) was applied. Out of a set of 826 studies, 23 were included in this systematic review. The main findings provided information about a shift towards modified eating behaviours, characterized by an increased snack frequency and a preference for sweets and ultra-processed food rather than fruits, vegetables, and fresh food. Additionally, an increased alcohol consumption was found among different countries. Consequently, adherence to healthy diets decreased. These findings are relevant to future policies and strategies to assess nutrition in cases of alarming situations such as the current COVID-19 pandemic.
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No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data.
Amin, HA, Drenos, F
BMJ nutrition, prevention & health. 2021;4(1):42-48
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Vitamin D is commonly discussed in terms of bone health and calcium and phosphate homeostasis, however, evidence has started to emerge that it may also be involved in cancer, the cardiovascular system and inflammation. The aim of this study was to assess whether genetically increased vitamin D levels are associated with SARS-CoV-2 infection risk and COVID-19 severity. This study is based on data from genome-wide association studies for vitamin D levels, vitamin D deficiency and COVID-19 incidence and severity. Results show no evidence that vitamin D is causally related to COVID-19 outcomes and there is no evidence to suggest that current National Institute for Health and Care Excellence guidance should change to support the use of vitamin D supplementation against COVID-19. Authors conclude that their findings support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
Abstract
BACKGROUND Upper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19. METHODS We used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity. RESULTS We found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI -0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI -0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=-0.04 (95% CI -0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=-0.24 (95% CI -0.55 to 0.08, p=0.14)). CONCLUSIONS In conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
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Vitamin D supplementation for the treatment of COVID-19: a living systematic review.
Stroehlein, JK, Wallqvist, J, Iannizzi, C, Mikolajewska, A, Metzendorf, MI, Benstoem, C, Meybohm, P, Becker, M, Skoetz, N, Stegemann, M, et al
The Cochrane database of systematic reviews. 2021;5:CD015043
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This study is part of a series of Cochrane Reviews investigating treatments and therapies for coronavirus disease 2019 (COVID-19). COVID-19 is a rapidly spreading infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic interventions to treat COVID-19 are being investigated with immense emphasis. Recently, vitamin D supplementation for treatment of COVID-19 gained attention, since studies suggested an association between vitamin D deficiency and risk or prognosis of the disease. The aim of this study was to assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 This study is a living systematic review of seven records (three randomised controlled studies – 356 adult participants). Results for the effectiveness of vitamin D supplementation for participants with COVID-19 are inconclusive. Moreover, inconsistency in the reporting of adverse and serious adverse events impeded evaluation of safety of vitamin D supplementation. Authors conclude that to elucidate the effectiveness and safety of vitamin D supplementation for individuals with COVID-19, more randomised controlled trials are needed.
Abstract
BACKGROUND The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7, whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.