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Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study

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... The sample size of the studies ranged from 134 to 79,381. The studies were conducted in Europe (14,(20)(21)(22)(23)(24)(25), America (26,27), and Asia (28)(29)(30)(31)(32). Moreover, the studies were cohort studies (14,22,25,27,30), case-control studies (20,21,26,31,32), cross-sectional studies (23,28,29) and interim audit (24) (see Table 1). ...
... The studies were conducted in Europe (14,(20)(21)(22)(23)(24)(25), America (26,27), and Asia (28)(29)(30)(31)(32). Moreover, the studies were cohort studies (14,22,25,27,30), case-control studies (20,21,26,31,32), cross-sectional studies (23,28,29) and interim audit (24) (see Table 1). ...
... A population-based study from Israeli also reported that low plasma 25(OH)D level appears to be an independent risk factor for COVID-19 infection and hospitalization (22). Also, it was indicated that the odds of death were higher in COVID-19 cases with insufficient vitamin D status (28,30). ...
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Background: Coronavirus disease (COVID-19) is a respiratory and systemic disorder caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or novel Coronavirus (nCoV). To date, there is no proven curative treatment for this virus; as a result, prevention remains to be the best strategy to combat coronavirus infection (COVID-19). Vitamin D deficiency (VDD) has been proposed to play a role in coronavirus infection (COVID-19). However, there is no conclusive evidence on its impact on COVID-19 infection. Therefore, the present review aimed to summarize the available evidence regarding the association between Vitamin D levels and the risk of COVID-19 infection. Methods: A systematic literature search of databases (PUBMED/MEDLINE, Cochrane/Wiley library, Scopus, and SciELO) were conducted from May 15, 2020, to December 20, 2020. Studies that assessed the effect of vitamin D level on COVID-19/SARS-2 infection were considered for the review. The qualities of the included studies were evaluated using the JBI tools. Meta-analysis with a random-effects model was conducted and odds ratio with their 95%CI were reported. This systematic review and meta-analysis are reported according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. Results: The electronic and supplementary searches for this review yielded 318 records from which, only 14 of them met the inclusion criteria. The qualitative synthesis indicated that vitamin D deficient individuals were at higher risk of COVID-19 infection as compared to vitamin D sufficient patients. The pooled analysis showed that individuals with Vitamin-D deficiency were 80% more likely to acquire COVID-19 infection as compared to those who have sufficient Vitamin D levels (OR = 1.80; 95%CI: 1.72, 1.88). Begg’s test also revealed that there was no significant publication bias between the studies (P = 0.764). The subgroup analysis revealed that the risk of acquiring COVID-19 infection was relatively higher in the case-control study design (OR = 1.81). Conclusions: In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serumis associated with a significantly decreased risk of COVID-19 infection.
... 24 Our study noted that a considerable number of pediatric patients suffering from COVID-19 had low vitamin D levels. A study by Molla et al. assessed the importance of nutrition in the regulation of the immune system, and it was found that most of the pediatric COVID-19 patients were deficient in Vitamin D. 15 The pathology of COVID-19 provokes release of inflammatory mediators due to the complex interaction between the virus 26 It was also found that vitamin D has a clear impact on disease severity and hence COVID associated mortality. As a result, there is a policy implication adopted by various regulatory bodies, where vitamin D supplementation has been recommended in deficient adults. ...
... Patients with high fever had deficient or insufficient levels of Vitamin D. Although adequate studies are not available assessing the role of vitamin D and disease severity in pediatric patients, several studies have shown that children with insufficient or deficient levels of vitamin D are more susceptible to respiratory infections. 27 Raharusun et al., observed mortality in 26 Also previous studies found an inverse correlation between vitamin D level and pneumonia severity, increased risk of sepsis, CRP level and ARDS risk. [28][29][30][31] Vitamin D is known as 'sunshine vitamin', as sunlight helps in the conversion of 7-dehydrocholesterol in the skin to • There is an association between vitamin D deficiency and clinical severity in pediatric COVID-19 cases. ...
Article
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Aim: We aim to study the relationship between vitamin D level, risk and severity of COVID-19 infection in pediatric population through systematic review. Methods: We searched PubMed, CINAHL, EMBASE, Cochrane Library and Google Scholar from December 2019 to June 2021 for retrieving articles studying association between vitamin D deficiency with COVID-19. Qualitative details were synthesized in evidence table and quantitative data was used for deriving pooled estimate through meta-analysis. Results: After initial search of 2261 articles, eight eligible studies (two reviews) were included in the systematic review. Meta-analysis of the quantitative data (six studies) showed pooled prevalence of vitamin D deficiency as 45.91% (95% CI : 25.148-67.450). In infected pediatric patients, low levels of vitamin D increased the risk of severe disease (odds ratio - 5.5; 95% CI : 1.560- 19.515; p = 0.008). It was also found that children and adolescents having vitamin D deficiency had greater risk of COVID infection as compared to patients with normal vitamin D levels. Improvement in disease severity with vitamin D supplementation was also noted. Conclusion: The systematic review showed that almost half of the pediatric COVID patients suffer from vitamin D deficiency. It is also clear that the low level of vitamin D is associated with greater risk of infection and poorer outcome in pediatrics.
... However, further search using the reference list of related articles and other databases yielded six articles. [55][56][57][58][59][60] (Table 2). The average period till publication was 33 days. ...
... However, this website does not distinguish retraction and withdrawal of papers. 79 Based on our search criteria, we pointed to six retracted papers related to COVID-19 treatment as shown in Table 2. [55][56][57][58][59][60]80 Authors have raised the concern that the results of some retracted papers could be used and cited in another publications and quickly spread through the social media before or without knowing the retraction of the original paper. 80 In contrast to the high number of COVID-19 publications which were believed to be based on high quality data, the retractions of two articles from prestigious journals in 2020 such as The New England Journal of Medicine (NEJM) and The Lancet, raised concerns about the ethical standards applied in these studies as well as the expedited peer-review process by these journals. ...
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The current COVID-19 pandemic situation has stimulated an unplanned clinical research paradigm which is evident from the surge of clinical trial registrations and the increasing number of COVID-related publications. We aimed to explore the standards for research conduction, publications and retraction of articles related to COVID-19 pharmacotherapy research during the pandemic. We analysed data from the contemporary literatures on studies reporting pharmacological agents for COVID-19 using MEDLINE, PubMed, WHO database and Google Scholar between January 01, 2020 and March 20, 2021. The initial search revealed a total of 61,801 articles. Based on the inclusion criteria, a total of 124 studies related to various pharmacological agents were included in the final analysis. Most of the studies were reported from the United States ( n = 30, 24%). Of the 124 studies, 50 (40%) were randomized controlled trials (RCTs). Immunomodulatory drugs-related ( n = 17, 34%) and COVID-19 vaccine-related studies ( n = 14, 28%) were the main topics in the relevant RCTs. The median days for dissemination of findings in journals were 114 days (IQR 61–189). A comparative analysis revealed that RCTs were disseminated earlier (median 79 days; IQR 52–131) when compared to observational studies (median = 144 days; IQR 69–206) ( p = 0.003). Six papers were retracted from high impact journals; in which the average period till publication was 33 days. Retraction of papers occurred within 10–48 days. Expedited reviews, research approval and early publications of COVID-19 related pharmaceutical studies could have an impact on the quality of publications. However, the huge number of publications in short time creates confusion for readers during the early phases of the pandemic. Retraction of papers is alarming but ensures research integrity and correctness of scientific information. These abbreviated processes could affect patient care and public awareness. It is imperative to follow rapid but rigours ethical standards for research approval and peer-review process for publications during health pandemics.
... Based on the data, it has been suggested that vitamin D supplements can alleviate the clinical course of COVID-19 and be used as an effective treatment method [9,10]. A few adult studies have demonstrated an association between vitamin D deficiency and COVID-19 severity and mortality [11,12]; however, pediatric data are scarce. ...
... A negative correlation has also been found between mean vitamin D levels and the number of COVID-19 cases in different countries [10]. Vitamin D deficiency has been reported to be associated with worse clinical outcomes and mortality in adult COVID-19 cases [11,12]. Pediatric research evaluating vitamin D levels and COVID-19 in terms of clinical severity and inflammation markers is scarce. ...
Article
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Vitamin D has an immunomodulating property that regulates the inflammatory response. In this study, the aim was to evaluate the relationship between vitamin D levels and clinical severity and inflammation markers in children and adolescents with COVID-19. The clinical and laboratory records of 103 pediatric cases with COVID-19, whose vitamin D levels had been measured, were retrospectively reviewed. The cases were divided into groups according to their clinical severity (asymptomatic, mild, and moderate-to-severe) and vitamin D levels. The moderate-to-severe clinical group had significantly higher inflammation markers (CRP, procalcitonin, fibrinogen, d-dimer) and a lower lymphocyte count compared to both the mild and asymptomatic groups. The 25 OH vitamin D levels were also significantly lower (p < 0.001), and the ratio of vitamin D deficiency was 70.6% in the moderate-to-severe group. The vitamin D–deficient group had a significantly higher age and fibrinogen levels while also having a lower lymphocyte count compared to the insufficient and normal groups. The 25 OH vitamin D level was correlated positively with the lymphocyte count (r = 0.375, p = <0.001), and negatively with age (r = −0.496, p = <0.001), CRP (r = −0.309, p = 0.002) and fibrinogen levels (r = −0.381, p = <0.001). In a logistic regression analysis, vitamin D deficiency, d-dimer, and fibrinogen levels on admission were independent predictors of severe clinical course.Conclusion: This study revealed an association between vitamin D deficiency and clinical severity, in addition to inflammation markers in pediatric COVID-19 cases. Prophylactic vitamin D supplementation may be considered, especially in the adolescent age group. What is Known: • • The pathology of COVID-19 involves a complex interaction between the SARS-CoV-2 and the immune system. Hyperinflammation/cytokine storm is held responsible for the severity of the disease. • Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection. What is New: • • Clinically more severe group had significantly lower vit D levels and significantly higher inflammation markers. • Lower 25 OH vit D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response.
... From Southeast Asia, a study on 780 patients infected with COVID-19 in Indonesia [55], reported significant comorbidity in 80 % of patients with vitamin D deficiency. In this pre-print yet significant study, mortality was significantly higher with insufficient vitamin D status, (OR = 7.63; p < 0.001). ...
... Similarly, in vitamin D deficient cases, the odds of mortality were 10.12 greater compared to patient with normal concentration, (OR = 10.12; p < 0.001) [55]. Nevertheless, with emerging evidence from observational data, there is heightened need for experimental studies and intervention trials to understand the role of vitamin D in COVID-19 outcomes. ...
Article
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The COVID-19 pandemic requires a rapid understanding of the pathogenesis of the spectrum of the disease and factors associated with varied clinical presentations. Immune dysregulation with a cytokine storm (CS) progressing to ARDS with resemblance to sHLH is suggested as a main cause of tissue injury. Low levels of vitamin D were observed in COVID-19 cases with higher incidence of mortality in 20 European countries, increased risk of severity in COVID-19 contributing to ARDS or fulminant myocarditis and micro vascular thrombosis is proposed. Vitamin D may be protective against acute respiratory tract infections, as it regulates the inflammatory cytokine response of respiratory epithelial cells and macrophages, suppress CS and other manifestations seen in SARS-Cov-2. Hence, it is suggested as one of the therapies in SARS-CoV-2 infection. Major research gaps are identified globally in clinical management and this relationship. There is an imperative requisite to understand the interplay of markers in SARS-CoV-2, its risk factors and potential role of vitamin D to improve clinical outcome by pandemic of COVID-19. We therefore perform this review for understanding the pathophysiology of SARS-CoV-2 infections and the role of vitamin D in combating it.
... Also, multiple studies have advocated role of vitamin D deficiency in COVID-19 severity and mortality [9][10][11][12][13][14][15][16]. In addition to its probable role to COVID, vitamin D deficiency has been associated with fatigue, muscle pain and weakness, together included under fibromyalgia syndrome [17,18]. After the partial release of this lockdown, many citizens have increased their physical activity and subsequently complained of body pains, which has an association with Vitamin D levels. ...
... In addition, several studies have attempted to ascertain any relationship between vitamin D deficiency and COVID-19 morbidity and death. These studies suggest the role of vitamin D in preventing viral multiplication and cause immunomodulation to decrease inflammatory damage in COVID-19 infection [10][11][12][13][14][15][16][17][18]20]. A recent study in the United States has showed that both sunlight and vitamin D in combination can be related to reduced risk of infection and death by COVID-19 [17]. ...
Article
AimsTo evaluate vitamin D3 levels in patients who presented with increased musculo-skeletal pain after release of lockdown period when compared to pre-lockdown status.IntroductionDuring this COVID pandemic, many countries have implemented lockdown measures and people have to work from home and many students and workers have to restrict themselves to home. During this period, their outdoor activities were limited. After the partial release of this lockdown many of them started to have some kind of physical activity and started experiencing body pains. We evaluated such patients for vitamin D3 levels and symptoms of fibromyalgia.Methods This is a retrospective analysis of patients from age group 18–60 presented to outpatient department or on telephonic consultation after partial release of lockdown. All patients who had mild back ache before lockdown and had symptoms exaggerated during this lockdown release were included. All patients were investigated for vitamin D3, PTH, thyroid profile, liver functional and kidney functional tests.ResultsOut of 120 patients presented to us in a period of 3 months, 31 patients had increased symptoms when compared to pre-lockdown status. 20 out of 31 patients had low vitamin D3 levels. 14 patients also developed symptoms of fibromyalgia.Conclusion There might be many reasons for increased pain during lockdown, but we focussed specially only on vitamin D3 because of its association with increased symptoms of COVID-19. This is a gentle reminder to test for vitamin D3 levels and supplement if found deficient.
... The final yield included 43 original articles. Nine studies were not peer-reviewed and therefore excluded (35)(36)(37)(38)(39)(40)(41)(42)(43). We extracted data from 31 peer-reviewed observational studies, and 3 RCTs, that reported on vitamin D status and COVID-19 infection and/or health related outcomes. ...
... We also excluded non peerreviewed articles to enhance the quality of the evidence. The quality of the research is crucial and due to the rapid dissemination of articles during the COVID-19 pandemic, it has been subjected to many flaws and weaknesses (35,96). This systematic review and meta-analysis therefore presents a thorough and reliable review and analysis of the available evidence, and a comprehensive overview of on-going clinical trials, based on a systematic search of the major trial registries. ...
Article
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Background Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes. Methods We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses. Results We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level < 20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95%CI [−9.5, −2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/d, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/d, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes. Conclusion While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.
... Literature searches found the application of nutritional interventions (mostly of vitamin C and vitamin D) in few countries like China, Italy, the USA and Iran, and some other countries. They are also taking into account the application of those nutrients on coronavirus patients seriously (Table 3) [128,129,130,131,132,133,134,135,136]. ...
Article
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The novel coronavirus disease 2019 (COVID-19) has unfolded an unprecedented worldwide public health emergency with disastrous economic consequences. Around 96 million coronavirus cases have already been identified with over half a million deaths. Despite numerous efforts by the government as well as international organizations, these numbers are still increasing with a surprising rate. Although urgent and absolutely necessary, a reliable therapeutic or vaccine is still elusive and this status quo may remain for an uncertain period of time. Taken that into account, boosting up adaptive immunity through nutritional interventions may help subside this epidemic and save many lives. This review focuses on the nexus between a balanced diet and adaptive immunity, particularly, how a poor diet may lead to compromised immunity resulting in susceptibility to viral infections. Additionally, we discuss how nutrients (vitamins, minerals, trace elements) can be used as a tool to modulate immune response and thus impede viral infections. The study also summarizes nutritional recommendations to combat COVID-19 in different countries and territories as well as dietary sources of those key nutrients. Moreover, different nutritional intervention strategies based on different age groups, physiological and medical conditions were also included, and the challenges of nutritional interventions towards the care of COVID-19 patients are also discussed. Since the availability of a drug or vaccine is still uncertain, a balanced diet or nutrient therapy can be used as a robust strategy to combat COVID-19. Thus, we hope this review may help to make an informed decision with regard to diet choice both at individual level as well as clinical settings. Keywords MacronutrientsMicronutrientsCOVID-19SARS-CoV-2ImmunityComplicationsNutritionViral infection
... Lau revealed that VD insufficiency prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients and concluded that may be an underlying driver of COVID-19 severity [70]. Rharusun in his retrospective Indonesian cohort study revealed that majority of the death cases were older male with pre-existing condition and hypovitaminosis D. Majority of the COVID-19 cases with insufficient and deficient VD status died [71]. Bloukh conclude that adequate serum vitamin D levels are needed for the prevention of severe cases of COVID-19 [72,73]. ...
Chapter
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Recent research about the influence of vitamin D (VD) deficiency on the occurrence of viral infections suggests that children with VD deficiency have attenuated immune response. This, in turn, increases the severity of viral infections, especially those of the respiratory tract, that show a typical seasonality pattern during the winter months. Despite the immunization of children at the global level, outbreaks of influenza do frequently occur. Over the past months, we have witnessed that the explosive pandemic of the corona virus disease 2019 (COVID-19) has caused significant mortality in some countries. Numerous studies have shown that VD deficiency is increasingly prevalent worldwide, and that it is potentially associated with the onset of viral infections. Persons with hypovitaminosis D and subsequent secondary immunodeficiencies ought to be identified and treated, while preventive supplementation of VD should be recommended to the general population to avoid VD deficiency during the winter. In this way, the burden of viral infections on population health and economy could be reduced. This paper also reviews the influence of VD on infections caused by hepatitis B and C viruses, human papil-lomavirus, Epstein-Barr virus, Human herpes virus 6, herpes simplex virus, and human immunodeficiency virus.
... Is there objective evidence to support such target recommendations? [72] (Figure 16). ...
Article
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Covid-19 has presented the world with a multitude of different clinical faces. To date their linkage eludes. This article attempts to establish linkage using recent research results regarding blood groups, clinical findings, cytokines, epidemiology, and the CD147 receptor, the orphan sister of ACE2. The role of the immune system controlled by the RAS and vitamin D is explored and recommendations ventured.
... Their results revealed a negative correlation between mean levels of vitamin D and the number of COVID-19 cases in each country [33]. Similarly, in a cohort study of 780 confirmed cases of COVID-19 in Indonesia, Raharusuna et al. revealed a considerable association between vitamin D deficiency and mortality even considering the other contributing factors as age, pre-existing comorbidity, and gender [34]. In another study, Lau et al. assessed vitamin D levels in twenty COVID-19 patients admitted in the intensive care unit which demonstrated the evidence of vitamin D deficiency in 11 subjects supporting the association of vitamin D deficiency and COVID-19 severity [35]. ...
Article
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Background and aims Novel Coronavirus (COVID-19) first appeared in China in late 2019 which was rapidly spread worldwide. As the COVID-19 pandemic continues to spread, it is crucial to determine the prognostic factors contributing to the development of severe disease and higher mortality. Herein we aimed to evaluate the correlation between the severity and prognosis of patients with COVID 19 with serum 25(OH)D levels. Method This descriptive retrospective study was performed from March to April 2020 at a referral center for patients with COVID-19, Tehran, Iran. The data collection was performed by a checklist consisting of the demographic features and laboratory assessments consisted of serum 25(OH)D were evaluated and recorded. And investigate the relationship between serum 25(OH)D and clinical outcomes of patients. Result 205 patients with a mean age of 59.71 years were enrolled. Our findings did not reveal a significant difference in mean levels of vitamin between improved (34.09) and deceased patients (34.54). However, in patients with severe disease, there was a considerable difference in levels of vitamin D in improved and deceased patients (P.value: 0.021). According to our results, the mortality rate was slightly higher in men (odds ratio:2.2). Furthermore, the mean age (64.20 vs. 58.51) and the presence of at least two comorbidities (odds ratio: 2.40) were significantly higher in deceased patients. Conclusion In this study, we did not reveal a statistical difference in mean levels of vitamin D and the outcome of patients with COVID-19. We concluded that in patients with severe disease, vitamin D deficiency could affect the course of the disease and mortality, especially in comorbidity and older people.
... Because of the COVID-19 pandemic, the majority of studies have indicated a correlation between vitamin D deficiency and increased vulnerability to SARS-CoV-2 infection, emphasizing the significance of getting vitamin D levels back to usual. (19) (20) According to an observational study, patients with severe vitamin D deficiency have a 17.3% chance of severe COVID-19, while patients with average vitamin D levels have just a 14.6% risk, a discrepancy of 15.6 per cent. (21) These findings are significant because vitamin D boosts cellular immunity, regulates the adaptive immune response, and enhances antioxidant-related gene expression. ...
... 1,25(OH) 2 D binds to the vitamin D receptor (VDR) and, after forming a heterodimer with the retinoid X receptor (RXR), translocates into the cell nucleus. Once there, it binds to the vitamin D responsive element (VDRE) in the DNA and regulates the transcription of numerous genes [50,51,64]. ...
Article
Worldwide the pandemic of COVID-19 spreads rapidly and has had an enormous public health impact with substantial morbidity and mortality especially in high-risk groups, such as older people and patients with comorbidities like diabetes, dementia or cancer. In the absence of a vaccine against COVID-19 there is an urgent need to find supportive therapies that can stabilize the immune system and can help to deal with the infection, especially for vulnerable groups such as the elderly. This is especially relevant for our geriatric institutions and nursing homes. A major potential contributing factor for elderly is due to their high incidence of malnutrition: up to 80% among the hospitalized elderly. Malnutrition results when adequate macronutrients and micronutrients are lacking in the diet. Often missing in public health discussions around preventing and treating COVID-19 patients are nutritional strategies to support optimal function of their immune system. This is surprising, given the importance that nutrients play a significant role for immune function. Several micronutrients, such as vitamin D, retinol, vitamin C, selenium and zinc are of special importance supporting both the adaptive and innate immune systems. As suboptimal status or deficiencies in these immune-relevant micronutrients impair immune function and reduces the resistance to infections, micronutrient deficiencies should therefore be corrected as soon as possible, especially in the elderly and other vulnerable groups. According to epidemiological, experimental and observational studies, some case reports and a few intervention studies the supplementation of vitamin D and/or zinc are promising. The multiple anti-inflammatory and immunomodulatory effects of Vitamin D could explain its protective role against immune hyper reaction and cytokine storm in patients with severe COVID-19. A randomized, placebo-controlled intervention study even shows that high dose vitamin D supplementation promotes viral clearance in asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals. Besides, the data of a recent prospective study with COVID-19 patients reveal that a significant number of them were zinc deficient. The zinc deficient patients had more complications and the deficiency was associated with a prolonged hospital stay and increased mortality. Thus, immune-relevant micronutrients may help to increase the physiological resilience against COVID-19.
... Based on several observational studies [21,22,97,99,102,105] and through a randomized pilot study conducted in Spain [28], it was found that people with COVID-19 require a sufficient level of vitamin D to prevent severity. The effects of vitamin D will be more significant in people with low vitamin D levels. ...
Article
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The foremost mortality-causing symptom associated with COVID-19 is acute respiratory distress syndrome (ARDS). A significant correlation has been identified between the deficiency in vitamin D and the risk of developing ARDS. It has been suggested that if we can reduce or modify ARDS in COVID-19 patients, we may significantly reduce the severity of COVID-19 symptoms and associated mortality rates. The increased mortality of dark-skinned people, who have a reduced UV absorption capacity, may be consistent with diminished vitamin D status. The factors associated with COVID-19 mortality, such as old age, ethnicity, obesity, hypertension, cardiovascular diseases, and diabetes, are all found to be linked with vitamin D deficiency. Based on this review and as a precautionary measure, it is suggested that the adoption of appropriate and safe solar exposure and vitamin D enriched foods and supplements should be considered to reduce the possible severity of COVID-19 symptoms. Safe sun exposure is deemed beneficial globally, specifically in low and middle income countries, as there is no cost involved. It is also noted that improved solar exposure and vitamin D levels can reduce the impact of other diseases as well, thus assisting in maintaining general human well-being.
... Also, Logistic regression showed insignificant relationship between vitamin D levels and death rate. reported to be associated with COVID-19 mortality comparing with normal group (16). ...
Article
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Background: Since beginning of Coronavirus disease of 2019 (COVID-19) pandemic, there were contradictions and speculations around vitamin D and COVID-19 relationship. Given that there is association between vitamin D deficiency and some diseases including cancer, autoimmune disease and some infectious diseases, COVID-19 higher incidence rate and mortality in vitamin D deficient population was not a surprise. Conversely, some research would argue this relationship. Considering these contradictions, the aim of this study was to determine the relationship between prognosis and vitamin D level in cases with COVID-19. Methods: In this cross-sectional study, 329 confirmed cases of COVID-19 which admitted to Kamkar-ArabNia Hospital in Qom city, Iran from March to July 2020 were categorized into three groups according to vitamin D serum levels (ng/ml): sufficient (>30), insufficient (20-30) and deficient (<20). Prognosis was determined across the groups. Results: There was significant difference in hospital stay between patients with sufficient and insufficient vitamin D levels (P = 0.007). Adjusting vitamin D levels for confounding variables, linear regression underscored significant differences in the association between length of hospitalization and lower vitamin D levels, with a longer stay noted in insufficient groups (P = 0.002). However, there was no significant difference in the time interval to return to normal oxygen level (from SpO2 below 93%) or death rate between groups (P > 0.05). Conclusion: There is significant association between hospital stay and lower serum vitamin D levels. However, the relationship between vitamin D status and death rate or the time interval to return to normal oxygen levels is not significant.
... A study from the Philippines found that, in 212 COVID-19 hospitalized patients, vitamin D status was associated with clinical outcomes, such that for each SD increase in 25(OH)D concentration, the odds of having a mild clinical outcome rather than a severe or critical outcome were 7.94 and 19.61, respectively (CI not reported) (244). A study of 780 COVID-19-positive hospitalized patients found that, after correction for age, sex, and comorbidity, the OR of death was 10.2 (P < 0.0001; 95% CI not reported) in cases with VDD (defined as <50 nmol/L) compared with "normal" vitamin D status (defined as 75 nmol/L) (245). However, this study has since been discredited (246). ...
Article
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Background Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. Objective The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. Methods We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020. Results Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. Conclusions Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.
... (47) En Indonesia, en 780 casos confirmados, los fallecidos fueron el 46,7% de los deficientes, el 49,1% de los insuficientes (entre 20 y 30 ng/ml) y solo el 4,2% de los que tenían un nivel mayor de 30 ng/ ml. (48) Finalmente, en Irán se reportó que falleció el 20% de los internados con menos de 30 ng/ ml y el 9,7% con un valor mayor. Es interesante el hecho de que en el grupo que tenía más de 40 ng/ml al ingreso, tuvo 6,3% de decesos, lo que confirmaría que 40 ng/ml de 25 vitamina D podría dar más protección. ...
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The discovery that the synthesis of 1-25-vitamin D is not only renal and that the enzyme 1 alpha hydroxylase is found in numerous tissues of the body, together with the evidence of the association between vitamin D deficiency and the presence of non-bone diseases (cancer, multiple sclerosis, autoimmune diseases, etc.), gives us the possibility of trying to prevent these conditions. Placebo-controlled supplementation studies have not provided positive results for certain conditions, but some of these trials have been carried out on populations with “sufficient” and not “deficient” vitamin D levels. However, other meta-analyses have shown prevention of some conditions (respiratory infections, prediabetes) in groups of patients with deficiencies who were given supplements. There is also evidence of antiviral effect of vitamin D. Its anti-infective and immunomodulatory action and its effect upon the renin–angiotensin system, stimulating the angiotensin-converting enzyme 2 (the SARS-CoV virus receptor), nowadays allow us to think that, in high levels, COVID-19 infection could be less likely or serious. Vitamin D supplementation is adequate for preventing diseases in patients with deficiencies; administering vitamin D within the 2020 pandemic, even without having tested it in high-risk populations, could diminish the incidence of this disease. © 2020, Asociacion Regional de Dialisi y Transplantes Renales de Capital Federal y Provincia de Buenos Aires. All rights reserved.
... D vitamini profilaksisinin özellikle hipovitaminozu olan hastalarda SARS-CoV-2'nin neden olduğu hastalığın şiddetini azaltabileceği varsayılmaktadır (24). Endonezyada yapılan 780 COVID-19 vakayı içeren retrospektif kohort çalışması, normalin altında D vitamini seviyeleri olan yaşlı ve erkek vakaların daha yüksek ölüm oranları ile ilişkili olduğunu bildirmiştir (25). SONUÇ D vitamini düzeyleri ile COVID-19 şiddeti ve mortalitesi arasındaki ilişki konusunda yeterli kanıt henüz yoktur. ...
... An inter-study heterogeneity was found (Chi 2 P<0.00001, I 2 =94%), and its source was due to studies by Jain and colleagues [42] and Raharusuna and colleagues [55] (Supplementary Fig. 2B). When these studies were excluded from the analysis, the funnel plot showed homogeneity of the remaining studies (Chi 2 P = 0.15, I 2 =36%), and the increased mortality risk for COVID-19 in presence of VDD was confirmed to be non-significant [OR 1.30 (0.83, 2.03); p = 0.23]. ...
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Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19. Methods Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: “Vitamin D”, “25 hydroxy Vitamin D”, “25 hydroxycholecalciferol”, “cholecalciferol”, “COVID 19″, “SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25‑hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D <20 ng/ml, were also included. We calculated the mean difference (MD) and the 95% confidence intervals (CI) for quantitative variables such as 25(OH)D levels in patients with or without SARS-CoV-2 infection, in those with mild vs. severe COVID-19, or those who have died vs. those who have been discharged. Instead, we calculated odds ratios and 95% CI for qualitative ones, such as the number of patients with severe illness/death in the presence of VDD vs. those with normal serum 25(OH)D levels. A p-value lower than 0.05 was considered statistically significant. The study was registered on PROSPERO (CRD42021241473). Findings Out of 662 records, 30 articles met inclusion criteria and, therefore, were included in the meta-analysis. We found that the serum levels of 25(OH)D were significantly lower in patients with SARS-CoV-2 infection than in negative ones [MD -3.99 (-5.34, -2.64); p <0.00001; I²= 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I²=98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p = 0.0005; I²=86%]. Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I²=84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p = 0.08; I²=94%]. Interpretation This meta-analysis revealed a large heterogeneity of the studies included due to the different enrolment criteria of patient samples (age, body mass index, ethnicity, comorbidities), the country where they live, all factors influencing serum 25(OH)D levels, and the different criteria used to define the severity of COVID-19. Furthermore, the observational nature of these studies does not allow to establish a cause-effect relationship, even taking into account that 25(OH)D represents a marker of acute inflammation. Treatment with vitamin D might be considered for the primary prevention of SARS-CoV-2 infection and the management of patients with COVID-19. However, further intervention studies are needed to prove this hypothesis.
... 12,13,33 In another study, it was determined that the vitamin D levels of 780 adults who died due to COVID-19 were lower than the normal reference values. 34 It was determined in our study that mothers used a wide variety of herbs and spices, the number of which was 33, to protect their children from COVID-19. Limited information is available about the benefits and risks of these products in the pediatric population. ...
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ABSTRACT Objective: The study aimed to examine the practices of mothers regarding the use of supplements, herbs-spices and child nutrition during the coronavirus disease-2019 (COVID-19) pandemic lock-down in a sample of Turkish mothers. Material and Methods: This descriptive and cross-sectional study conducted in Karabük province of Türkiye. 565 mothers with children aged 2-18 participated in the study. For data collection, a questionnaire was used to evaluate the foods consumed by children and the practices of mothers on child nutrition. Descriptive statistical methods, and the chi-square test for differences between groups in terms of categorical variables was used. Results: Eighty-nine percent of mothers had used at least one product to protect their children from COVID-19. While the use of supplements by the mothers was 62%, the use of herbs and spices was 74%. A significant difference was found between the type of product used by the mothers and the state of mothers' being informed about the use of any product (Psupplement<0.001; Pherbs-spices<0.001). Conclusion: Especially the mothers who resorted to these products used them without getting any information. In order for parents to access evidence-based information on child nutrition, training given by health professionals in a virtual learning environment is important for mothers to learn proper nutrition practices.
... However, the comorbid factors concomitant with the majority of those with deficient and insufficient vitamin D levels in their studies make it difficult to evaluate the relationship between mortality and vitamin D alone. 25 The pathology of COVID-19 involves a complex interaction between the virüs and the body immune system. COVID-19 is provoke, the release of proinflammatory cytokines. ...
Article
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Background: Vitamin D deficiency is a major public health problem in all age groups. Through its immunomodulatory, anti-inflammatory and antioxidant effects it is shown to have a protective effect in COVID affected children. The objective of the study was to evaluate vitamin D deficiency as a risk factor for developing COVID-19 infection in children and to study the relationship between vitamin D deficiency and the clinical findings in COVID-19 positive children.Methods: A retrospective study of all COVID positive children aged 1 month to 15 years admitted to COVID Paediatric ward of Rajarajeshwari Medical hospital from July 2020-November 2020. All COVID positive children confirmed with RTPCR of age group 1 month to 15 years will be included in the study the age at admission, clinical and laboratory data, and 25‐hydroxycholecalciferol (25‐OHD) levels will be recorded. Patients diagnosed with COVID 19 are divided into 2 groups those with deficient and insufficient vitamin D levels were determined as group 1 and patients with normal vitamin D levels as Group 2. Those with vitamin D Levels below 20ng/ml were determined as group 1 and those with >20 ng/ml as group 2. The various clinical outcomes and laboratory parameters were compared between the two groups.Results: Patients with COVID 19 had significantly lower vitamin D levels 22.39±6.27 (p≤0.0001). Patients in group A that is vitamin D deficient and insufficient group had higher levels of ferritin (p≤0.0001).No significant difference was found between other clinical and laboratory parameters between group 1 and group 2.Conclusions: This is one of the first to evaluate vitamin D levels and its relationship with clinical findings in paediatric patients with covid-19. Although vitamin D does not play a role in the pathogenesis of COVID-19 we do believe its putative role in preventing and treating the disease The results suggest that vitamin D levels may be associated with the occurrence and management of the COVID-19 disease by modulating the immunological mechanism to the virus in paediatric population.
... With the recent findings of the immunomodulatory effect of 25-hydroxyvitamin D [25(OH)D] (i.e., decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines 5 ), a possible association between serum vitamin D levels and the clinical course due to COVID-19 has been hypothesized. Thus, some studies demonstrate a relationship between 25(OH)D deficiency severity and mortality from COVID-19 6,7 ; however, data on this association in pediatric patients are still lacking. ...
... Analyses did not adjust for potentially confounding factors such as age and comorbidities. In one study unique for reported assessment of prehospitalization vitamin D levels, Raharusuna et al. 35 reported (not yet peer reviewed) substantially increased COVID-related mortality associated with prehospitalization 25(OH)D level <20 ng/ mL in 780 confirmed COVID-19 positive hospitalized cases in Indonesia. In this study, the overall mortality rate (48.7%) was considerably higher than in our study sample (23.7%), with a larger discrepancy in those aged 50 or more (78.8% ...
Article
Context: Populations severely affected by COVID-19 are also at risk for vitamin D deficiency. Common risk factors include older age, chronic illness, obesity, and non-Caucasian race. Vitamin D deficiency has been associated with risk for respiratory infections and failure, susceptibility and response to therapy for enveloped virus infection, and immune-mediated inflammatory reaction. Objective: To test the hypothesis that 25-hydroxyvitamin D[25(OH)D] deficiency is a risk factor for severity of COVID-19 respiratory and inflammatory complications. Design: We examined the relationship between prehospitalization 25(OH)D levels (obtained 1–365 days prior to admission) and COVID-19 clinical outcomes in 700 COVID-19 positive hospitalized patients. Primary Outcomes: Discharge status, mortality, length of stay, intubation status, renal replacement. Secondary Outcomes: Inflammatory markers. Results: 25(OH)D levels were available in 93 patients [25(OH)D:25(IQR:17–33)ng/mL]. Compared to those without 25(OH)D levels, those with measurements did not differ in age, BMI or distribution of sex and race, but were more likely to have comorbidities. Those with 25(OH)D < 20 ng/mL (n = 35) did not differ from those with 25(OH)D ≥ 20 ng/mL in terms of age, sex, race, BMI, or comorbidities. Low 25(OH)D tended to be associated with younger age and lower frequency of preexisting pulmonary disease. There were no significant between-group differences in any outcome. Results were similar in those ≥50 years, in male/female-only cohorts, and when differing 25(OH)D thresholds were used (<15 ng/mL and <30 ng/mL). There was no relationship between 25(OH)D as a continuous variable and any outcome, even after controlling for age and pulmonary disease. Conclusions: These preliminary data do not support a relationship between prehospitalization vitamin D status and COVID-19 clinical outcomes.
... In a sample of 780 hospitalized patients testing positive for COVID-19 in Indonesia, the odds ratio of death was higher in older and male cases with pre-existing conditions and below normal vitamin D levels. After controlling for age, sex, and comorbidity, both insufficient (OR ¼ 7.63) and deficient 25(OH)D levels (OR ¼ 10.12) were significantly associated with COVID-19 mortality (p < 0.001 for each) [58]. These similar findings were also observed in a large US cohort study (n ¼ 191,779) where SARS-CoV-2 positivity was inversely associated with circulating 25(OH)D levels after adjusting for latitudes, races/ethnicities, both sexes, and age ranges. ...
Article
The pathogenicity of the current coronavirus disease (COVID-19) shows postulates that optimal status of essential nutrients is crucial in supporting both the early viraemic and later hyperinflammatory phases of COVID-19. Micronutrients such as vitamin C, D, zinc, and selenium play roles in antioxidant, anti-inflammatory, antithrombotic, antiviral, and immuno-modulatory functions and are useful in both innate and adaptive immunity. The purpose of this review is to provide a high-level summary of evidence on clinical outcomes associated with nutritional risk of these micronutrients observed in patients with COVID-19. A literature search was performed on PubMed and Google Scholar to obtain findings of cross-sectional and experimental studies in humans. The search resulted in a total of 1212 reports including all nutrients, but only 85 were included according to the eligibility criteria. Despite the diversity of studies and the lack of randomized clinical trials and prospective cohorts, there is evidence of the potential protective and therapeutic roles of vitamin C, D, zinc, and selenium in COVID-19. The findings summarized in this review will contribute to guide interventions in clinical practice or in future clinical studies.
... The results of a meta-analysis revealed that serum 25(OH)D levels below 50 nmol/l (i.e.<20 ng/ml) increases the risk of community-acquired pneumonia up to 64% (68), Thus, a hypothesis has been put forward that vitamin D deficiency can increase the severity of COVID-19 infection as well as the mortality rate in these individuals (69,70). The association between vitamin D levels and the severity of COVID-19 mortality has already been reported in several retrospective studies (71,72). Vitamin D follows different mechanisms in reducing the risk of viral infections including COVID-19 and its resulting mortality; these mechanisms include maintaining cell junctions and gap junctions, increasing cellular immunity by decreasing the cytokine storm with an influence on interferon γ and tumor necrosis factor α and regulating adaptive immunity through inhibiting T helper cell type 1 responses and stimulating T cells (69). ...
Article
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The COVID-19 virus has caused many deaths of people worldwide since the pandemic began. However, no definitive treatment for this infection has been discovered so far. It has been shown that comorbidities such as diabetes, hypertension and cardiovascular diseases are associated with an increased risk of SARS-COV-2 infection. Interestingly, SARS-COV-2, like SARS-COV, uses the ACE2 gene to enter the host cell. Also, changes or imbalance in ACE2.ACE can affect SARS-COV-2 susceptibility, related outcomes and mortality. Regarding the crucial role of ACE2 protein in COVID-19 infection, the effect of different factors such as age, BMI, physical activity levels, nutritional status, altitude, as well as blood group was assessed on the level of this protein. Further, to our knowledge, no study has been conducted to examine factors that increase or decrease the risk of COVID-19 and its related severity and outcome in normal subjects emphasizing the pivotal role of ACE2. Therefore, the primary purpose of this study was to investigate the involved mechanisms of ACE2 protein and other risk factors causing infection in different situations and finally, to introduce a safe, accurate, and cost-effective approach to prevent SARS-COV-2 infection and hard clinical outcomes in normal subjects.
... When controlling for age, sex, and comorbidity, they found that vitamin D status was strongly associated with COVID-19 mortality outcome of cases. 71 A summary of their findings are in the impressive graph below that demonstrates a radical reduction in the death rate from COVID-19 as the vitamin D level increase to over 30 ng/ml. ...
Article
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Determining the trace element levels in the human hair is a significant analytical technique, a screening element in the evaluation of possible deficiencies, excesses, and/or biochemical imbalances in all bodies of these microelements. In this work of research, by an inductively coupled plasma– mass spectrometry (ICP-MS) analyzer, the authors have proposed the discovery of toxic trace elements (Al, Pb, Hg) and levels principal mineral elements (Ca, Mg, Cu, Zn) from the human body on healthy individuals with a good nutritional status. The study was performed on a sample of 75 adult women (30-35 years old) from different regions of the country, by taking 100 mg of hair from the base of the scalp with a length of 3 cm, for analysis and evaluation of trace elements. Twelve patients (16%) had high mean values of intracellular Mg (1.2 mmol / L), high Ca values (0.72 mmol / L), but low mean Ca / Mg ratios, (0.58). In addition, six patients (8%) had low mean values of Mg (0.004 mmol / L) and Ca (0.04 mmol / L) but a high Ca / Mg ratio. At the moment of analysis, all individuals did not have acute or severe intoxication signs with heavy metals. The environmental lifestyle of analyzed individuals, from various areas of the country, was observed in their hair cells, by present levels of trace elements. Copyright © 2013 - All Rights Reserved - Pharmacophore
... Analysis of preliminary medical statistics [1][2][3][4] has shown an important role of this vitamin in the regulation of the immune system in viral infections caused by coronavirus SARS-CoV-2. A large number of recent studies suggest that the status of vitamin D in the blood can determine both the risk of COVID-19 infection and the severity of the disease, as well as affect mortality from COVID-19 [5][6][7][8][9][10][11]. Vitamin D deficiency has been shown to be more likely to be observed in patients with laboratory-proven cases of COVID-19 [6]. ...
Article
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The aim of the work was to form ideas about rational nutrition as an element of ecological education of students by studying and discussing their eating behavior in relation to foods rich in vitamin D using quantitative descriptor-profile analysis. Quantitative descriptor-profile analysis showed that the “poorest” profiles have foods with the highest vitamin D. Thus, foods with a high vitamin D content do not fall into the circle of students’ dietary preferences. The results of the survey showed that the most frequently consumed foods for young people are fried potatoes, pizza, dumplings and cheese. Products such as cheese, butter, artificial red caviar, mushrooms (chanterelles) can be successfully used as a base for fortification with vitamin D, since they are positively perceived by students and affordable. It was shown that cheese is the only product that, when surveyed by 59 young people, was included both in the list of 5 most favorite and frequently consumed foods, and was selected from the list of 22 foods offered to the respondents containing significant amounts of vitamin D. The research carried out is the basis for forming students’ understanding of the importance of a balanced diet in the context of environmental education.
... 26 Another retrospective study reported a mortality rate of 98.9% in vitamin deficient covid cases. 27 Patients with COVID-19 are also at risk for a number of thrombotic complications and coagulopathy which is related to poor prognosis and increased mortality. 28 Their serum levels of cytokines are highly increased which is associated with morbidity and mortality. ...
Article
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The surge in the spread of the corona virus disease (COVID-19) pandemic alerted us to opt for the preventive medicine, as prevention is always better than cure. Apart from wearing mask, frequent hand washing and social distancing, strengthening our immune response plays a pivotal role in preventing infections. Vitamin D not only aids in calcium and phosphate homeostasis but also acts as an immunomodulator; the deficiency of which is linked with various respiratory and systemic infections. Hence we took up this review to study the effect of vitamin D in corona illness. Vitamin D exerts the expression of pro-inflammatory cytokines, hinders zinc metabolism, lowers Interleukin 6 levels and thereby inhibits cytokine storm in covid patients. Studies have proved that the covid patients have vitamin D deficiency and its supplementation improves the disease severity as well as the length of hospital stay. To conclude, Vitamin D supplementation can protect as well as halt the progression of corona virus disease. Further trials are needed to set the therapeutic levels in various stages of corona illness.
... Clinical studies showed that the most vulnerable populations for COVID-19 are the elderly population and those with vitamin D deficiency. 3 Older patients with comorbidities and below-normal vitamin D have a higher rate of mortality. 165 Vitamin D deficiency was also reported to be associated with an increased risk of severity in COVID-19. 166 It seems highly probable that appropriate supplementation of vitamin D for populations with a high prevalence of vitamin D deficiency may decrease the risk of severe COVID-19 consequences. ...
Article
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Vitamin D is proposed to have a potential role in the pathogenicity, clinical presentation, prognosis, complications, and treatment of several diseases. In addition to its well-known role in calcium metabolism, vitamin D regulates both innate and adaptive immunity, and subsequently modulates the antiviral and antibacterial inflammatory immune responses. In view of the emerging coronavirus disease 2019 (COVID-19) pandemic, searching for potential therapeutic and protective strategies is of urgent interest, and vitamin D is one of the promising agents in this field. In this review, we present data from literature that supports the promising role of vitamin D in treatment and/or prevention of several infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes vitamin D metabolism and its role in inflammation, thrombosis and immune regulation. It also reviews, in short, the role of vitamin D and the impact of its deficiency in several infections namely tuberculosis, influenza, human immunodeficiency virus (HIV), and SARS-CoV-2. Considering the roles of vitamin D on immune modulation, controlling of thrombosis, and attacking several microorganisms, the current review will elaborate on the association between these salient roles of vitamin D and the pathogenicity of various infectious agents including COVID-19. Consequently, the comprehensive finding of the current review shows a possible significant impact of vitamin D supplement as a hope in preventing, treating, and/or improving the progression of certain infections, specifically during the worldwide attempts to fight against the COVID-19 pandemic and minimize the severity of health complications encountered accordingly. In addition, avoiding a status of vitamin D deficiency to obtain its positive effects on the immune system and its protective mechanism during infections will be a general benefit overall.
... A second observatory study from Egypt investigated both NTproBNP and vitamin D levels in 100 COVID-19 patients and monitored disease progression [25]. Reduced vitamin D levels have been linked to disease severity [26][27][28]. High-dose vitamin D has shown to be antiviral, and, amongst other effects, it seems to stimulate the production of antimicrobial peptides in hosts; therefore, high-dose vitamin D is being studied in another clinical trial in Egypt [29]. A similar observational study performed in France evaluated NTproBNP and the high-sensitive cardiac troponin T (hs-cTnT) as potential markers for disease prognosis [30]. ...
Article
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Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview.
... In recent days numbers of reviews supported the possible role of vitamin D in decreasing the risk of COVID-19 infections and mortality [155,157,[191][192][193][194]. Vitamin D supplementation is also found to increase gene expression related to anti-oxidation (glutathione reductase modifier subunit) and by doing this, glutathione spares the use of vitamin C, which has potential antimicrobial activities [195][196][197], and has been suggested to prevent and treat COVID-19 infection [198,199]. The serum response to the given dose is largely varied between the individuals due to differences in demographic and biological variables, such as ethnicity, age, duration of exposure, seasonal variations, Body Mass Index (BMI), intake of certain medications, base-line concentration of vitamin D, genetics and type of vitamin D supplements [153,200,201]. ...
Article
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As of now, there is no specific preventive and curative medicine available to treat coronavirus disease 2019 (COVID-19), the best weapon to fight against this highly contagious disease is to boost our immune system. There are two paths of the immune system in our body, the innate and adaptive immune axis working 24/7 with their specialized sentinels capable of orchestrating responses against invading agents. These components of the immune system cannot work optimally in a nutrients deficient consortium. Micronutrient deficiency, called the hidden hunger occurs unknowingly when the quality of food people used to consume daily is not meeting the optimum requirement of vitamins and trace elements. In terms of immunity, the importance of crosstalk between the gastrointestinal (GI) tract microbiome with other distant organs, especially the respiratory system is a recent area of understanding. This review highlighted the contribution of macronutrients as well as the potential role of few vitamins, trace elements, and probiotics on preventive and therapeutic applications to strengthen the immune system along with gut homeostasis.
... Prabowo Raharusuna et al. 53 has done retrospective cohort study which determine the vitamin-D level and COVID-19 mortality outcome. The key findings of the research is that most of the COVID-19 patients with deficient vitamin-D level have high mortality. ...
Article
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An impasse in the realm of public health has been undergoing since December due to outbreak of COVID-19. As a consequence of this impasse, different countries are tumbling into an even deeper recession. The life of economically backward people came to a grinding halt on account of the recurrent lockdown. To bear the cost for the treatment of COVID-19 is nearly to impossible for them. It is well known fact that the best preventive measure against COVID-19 should be vitamin-D supplementation for those who are vitamin-D insufficient or deficient. Nearly 1 billion people worldwide have low level of vitamin-D. We know vitamin-D plays a vital role to the function of immune system and vitamin-D supplements have previously been proven safe and effective to reduce the risk of viral respiratory tract infection. Recently, some study have shown a strong relation between severe vitamin-D deficiency and death rate in COVID-19. It has been recorded that patients with lower level of vitamin-D had higher risk of death than patients having no deficiency in vitamin-D. Mortality rate is quite high in 20 European countries and in USA because the people of this countries are vitamin-D deficient. Thus, vitamin-D supplementation can be a very good preventive treatment against COVID-19.
... Four-hundred-thirteen studies were then excluded as they were case reports (n = 2), reviews (n = 137), meta-analysis (n = 9), editorial/letters (n = 112), or because they were not relevant for the aims of the present meta-analysis (n = 153). Two studies available as preprints until August 2020 were excluded since they were subsequently retracted (30)(31)(32). In addition, 7 studies were excluded due to incomplete data, mainly due to the lack of information concerning disease outcomes in relation to 25OHD thresholds (33)(34)(35)(36)(37)(38)(39) or because severe COVID-19 cases requiring intubation or mechanical respiratory support were not considered for 25OHD measurement (40). ...
Article
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Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45–4.77; 2.16, 1.43–3.26; 2.83, 1.74–4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93–3.49; 1.84, 1.26–2.69; 4.15, 1.76–9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32–2.13; 1.83, 1.43–2.33; 1.49, 1.16–1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63–3.85; 2.38, 1.56–3.63; 1.82, 1.43–2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change. Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.
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The world is foreseeing an ever-increasing human health crisis by virtue of threats from viral disease outbreaks recently showcased by COVID-19 and also those in the previous two decades by other coronaviruses. Many lives have been lost and various world economies have been constrained with the effect from the current pandemic. Corona-warriors, as the name is floating in the air, have also emerged in the shape of the medical and healthcare practitioners, fundraising charity trusts, and sanitation workforces, who are variously catering to the cause. On this mission, most scientific communities and pharmaceutical giants are also investing their best efforts toward studying the molecular biology of these pathogens and discovering and/or designing potential vaccine candidates against the notorious killers. The scenarios, however, have been felt graver with new mutant SARS-2 CoV strains hitting with sporadic emergence, complicating development and contradicting efficacies of these putative vaccines and standard therapies up close to dissemination into the public. Many viral and other pathogenic entities have been found to correlate their bases of pathogenesis and disease severity to, besides other factors, the development of pronounced oxidative stress. Abnormally generated and ill-regulated oxidative stress profiles are reported to effectuate severity, as seen in COVID-19 cases that may trigger cytokine/chemokine storms, ill-orchestrated NETosis, pyroptosis, and others that culminate into symptoms like colitis, ARD/DIC, endothelial dysfunction, coagulopathies, and graver chances of sepsis. Here, we narrate important studies with some of the potent antioxidant molecules which have surfaced with their promises at directly and/or indirectly evading the chances of COVID-19 and possibly other viral diseases. We present a compelling view of the various mechanistic networks within which CoV-led oxidative stress could detriment the homeostatic harmony within the cell/tissue systems by interfering with inflammatory and immunological stimuli and how the antioxidants emerge as a highly sought therapy.
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Background Although a vast knowledge has already been gathered on the pathophysiology of COVID-19, there are still limited, non-optimal treatment options. In this context, agents that can act on prophylaxis or as adjuvants to the therapies are of high value. Methods In this paper, we describe a multicentre, retrospective, observational study to describe the course of SARS-CoV-2 disease in patients treated with ImmunoFormulation (IF), an add-on therapy developed to decrease duration of clinical symptoms. In parallel, a group of patients that did not receive IF was used for comparison (using standard of care treatment). A total of 39 patients were evaluated for their recovery rate, general symptoms and their severity, and adverse reactions. Results Throughout the observational period, 90% of patients recovered in the IF cohort and 47.4% in the Control cohort (p=0.0057). From the symptoms with statistically significant differences, the duration of symptoms (i.e., the time to recover from it) was shorter in the IF cohort than in control cohort (in days, average), especially for fever (2.25 x 21.78), dry cough (4.38 x 24.00), dyspnoea (3.67 x 20.00), headache (2.00 x 26.50), diarrhoea (5.25 x 25.25), and weakness (1.92 x 23.30). Conclusions This demonstrates a potential promising role of IF as adjuvant therapy on the evolution of symptomatology to COVID-19 patients.
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Background and objective: Some studies have suggested a potential protective role of vitamin D in coronavirus disease 2019 (COVID- 19) patients, and this has led to a debate on the topic in the medical community. However, the reported data on the number of hospitalized patients who were vitamin D-deficient is not convincing. In light of this, the aim of the present study was to explore if vitamin D deficiency is correlated with severity and mortality rates of COVID-19 infection in hospitalized COVID-19 patients at a tertiary care hospital in Greece. Methods: We conducted a single-center retrospective study involving 71 patients hospitalized with COVID-19 from August to October 2020. Serum 25-hydroxyvitamin D (25(OH)D) level was assessed in all patients within 48 hours of hospital admission. Serum 25(OH)D level ≤20 ng/ml was defined as a deficiency, while that >20 ng/ml as repletion. The primary outcomes of the infection were classified as partial/complete recovery and mortality during hospitalization. The secondary outcomes were blood markers of inflammation and thrombosis. Results: Among the 71 COVID-19-positive patients [mean age: 63 years, range: 20-97; male (n=47; 66.2%): female (n=24; 33.8%)] who were enrolled in the study, 46 (64.8%) patients had 25(OH)D levels ≤20 ng/ml and 25 (35.2%) had a level >20 ng/ml. According to the patients' medical history, 55 patients (77.5%) had comorbidities. It appears that vitamin D deficiency (<20 ng/ml) significantly correlated with elevated biochemical markers such as procalcitonin and troponin (p<0.001). Moreover, male gender, advanced age (>60 years), and comorbidities were positively associated with more severe COVID-19 infection (elevated inflammation markers, radiographic findings on X-rays, and increased length of hospital stay). Conclusion: These preliminary findings show that vitamin D status among the patients was not related to the severity of COVID-19 infection.
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Aim - to determine the efficacy of drug aminodihydrophthalazinedione sodium (Galavit) for prevention of progression of the coronavirus infection pulmonary complications: acceleration of regression of pulmonary infiltrates and resolution of COVID-induced pneumonia. 22 patients with medium and severe COVID-induced pneumonia were included in the study. The study included 8 men and 14 women, the average age was 62.1±7.4 years. Patients with more than one adverse prognostic factor made 82%. Average volume of pulmonary tissue affection (computer tomography - CT-2, 25-50% of lung volume) was registered in 13 (59.1%) patients, significant volume (CT-3, 50-75% of lung volume), in 9 (40.9%) patients. All patients had progressive respiratory failure manifestations due to hypoxemia and related diseases. Aminodihydrophthalazinedione sodium was administered for 7-14 days from the beginning of disease, at the end of the course of standard complex therapy, in case of preservation of signs of intoxication, negative dynamics according to computer tomography data. Administration of aminodihydrophthalazinedione sodium had a positive effect on the dynamics of clinical scores. The progression of respiratory failure was halted and there was an increase in SpO2 values. According to the control computer tomography data the stabilization of the pulmonary parenchyma affection degree was noted, as well as reduction of the size of the compacted areas in the pulmonary tissue and formation of the picture of organising pneumonia that contributed to reduction of respiratory failure grade. The use of aminodihydrophthalazinedione sodium in complex therapy of COVID-induced pneumonia has a modulating effect on the immune system, prevents the progression of pulmonary tissue affection, promotes regression of infiltration foci, preventing the development of excessive pneumofibrosis and the progression of respiratory failure.
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Introduction: Vitamin D status is related to risks of influenza and respiratory tract infec�tions. Vitamin D has direct antiviral effects primarily against enveloped viruses, and cor�onavirus is an enveloped virus. The 2019 coronavirus disease had a high mortality rate and impacted the whole population of the planet, with severe acute respiratory syndrome the principal cause of death. Vitamin D can adequately modulate and regulate the immune and oxidative response to infection with COVID-19. The goal of this systematic review was thus to summarize and decide if there were a link between vitamin D status and COVID-19 infection and prognosis. Methods: The protocol of this study is documented in the Prospero database and can be accessed with the protocol number CRD42020201283. PubMed and Google Scholar were used for a literature search from August 2020 to September 2020. We restricted the year of publication of reviewed articles to 2019–2020, and the selected language was English. Studies that used secondary data, feedback, or analysis of reviews were removed. To assess the standard of studies included, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method was used. Results: Of the nine studies reviewed, seven (77.8%) showed that COVID-19 infection, prognosis, and mortality were correlated with vitamin D status. Conclusion: Most of the articles reviewed showed that blood vitamin D status can deter�mine the risk of being infected with COVID-19, seriousness of COVID-19, and mortality from COVID-19. Therefore, maintaining appropriate levels of Vitamin D through supple�mentation or natural methods, eg, sunlight on the skin, is recommended for the public to be able to cope with the pandemic.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a novel coronavirus has 28 rapid spread, and caused community infection around the globe. During the absence of a 29 vaccine, people focused more on an immunity-boosting diet and needed clear knowledge about 30 immunity-boosting foods. However, after the vaccination drive, the importance of food as a 31 natural source of immunomodulation cannot be neglected. So, the purpose of this review was 32 to describe the role of vital nutrient in boosting immune system of body apart from other factors 33 like adequate sleep, exercise, and low stress levels. Macrophages, neutrophils, natural killer 34 cells, dendritic cells, B-cells, and T-cells are the important components having important role 35 in maintaining immunity of the human body. The first four-act as the initial mediator of innate 36 host defense, and the latter two produced antibodies for pathogen destruction. The review 37 investigated vital nutrients like vitamin-C, A, E and D, iron, zinc, folic acid, probiotics, and 38 prebiotics affecting these immune components in some extent. Fruits, vegetables, spices, herbs, 39 seeds, nuts, cereals, millets, and superfoods like chlorella and spirulina are good sources of 40 these nutrients. However, fortified foods, functional foods, encapsulated foods with bioactive 41 compounds and plant-based foods have shown immense potential in boosting immunity against 42 viral infection like COVID-19. Some clinical trials and retrospective cohort study have shown 43 reduction in the severity of COVID-19 patients with relation to plant-based diet, vitamin D and 44 C doses, probiotic, and zinc salts application.
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Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.
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Background Retraction of published research can reduce the dissemination of incorrect or misleading information, but concerns have been raised about the clarity and rigor of the retraction process. Failure to clearly and consistently retract research has several risks, for example discredited or erroneous research may inform health research studies (e.g. clinical trials), policies and practices, potentially rendering these unreliable. Objective To investigate consistency and clarity of research retraction, based on a case study of retracted Covid-19 research. Study design A cross-sectional study of retracted Covid-19 articles reporting empirical research findings, based on searches of Medline, Embase and Scopus on 10 th July and 19 th December 2020. Key results We included 46 retracted Covid-19 articles. The number eligible for inclusion nearly doubled, from 26 to 46, in five months. Most articles (67%) were retracted from scientific journals and the remainder from preprint servers. Key findings: (1) reasons for retraction were not reported in 33% (15/46) of cases; (2) time from publication to retraction could not be determined in 43% (20/46) of cases; (3) More than half (59%) of retracted Covid-19 articles (27/46) remained available as original unmarked electronic documents after retraction (33% as full text and 26% as an abstract only). Sources of articles post-retraction were preprint servers, ResearchGate and, less commonly, websites including PubMed Central and the World Health Organization. A retracted journal article which controversially claimed a link between 5G technology and Covid-19 remains available in its original full text from at least 60 different websites. Conclusions The retraction process is inconsistent and often ambiguous, with more than half of retracted Covid-19 research articles remaining available, unmarked, from a wide range of online sources. There is an urgent need to improve guidance on the retraction process and to extend this to cover preprint servers. We provide structured recommendations to address these concerns and to reduce the risks that arise when retracted research is inappropriately cited.
Article
Introduction: Coronavirus disease 2019 (COVID-19) from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most important epidemiological events in the past 100 years has become, the consequences for public health and economic systems around the world. Vitamin D is an important micronutrient that has been reported to improve immunity and protect against respiratory diseases. In this study, we intend to review articles that examine the relationship between COVID-19 and vitamin D. Methods: This is a review that uses articles from studies published in 2020 on the relationship between COVID-19 and vitamin D in databases such as; Web of Science, Science Direct, SID, Magiran, Google Scholar and PubMed. Keywords used included; serum levels of 25-hydroxyvitamin D, vitamin D, COVID-19, SARS-COV-2 and coronavirus 2. With this search, 32 articles were finally selected for this purpose and their results were reviewed Results: Of the 32 studies reviewed, only three showed no association between vitamin D levels in the blood and COVID-19 disease. Other studies had a relationship between the severity of the disease, mortality rate and length of hospital stay, in different age, gender and location groups. Conclusion: It seems that the level of vitamin D in the blood has a potential effect on COVID-19 disease. Checking the serum vitamin D levels and supplementation in people with hypovitaminosis D can be a good solution to reduce the complications and problems caused by COVID-19.
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Severely ill COVID-19(Corona Virus Disease of 2019) patients have a hyperinflammatory condition with a high concentration of pro-inflammatory cytokines termed the cytokine storm. This milieu is reported to cause acute lung injury, oxygen deprivation, multiorgan damage, critical illness, and often death. Post SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) infection, the fight between the invading virus and the host's immune system would either terminate in recovery, with eradication of the infection and regulation of the immune system; or there would be a continuation of immune attacks even after the virus has been cleared, leading to immune dysregulation and disease. This outcome is chiefly dependent on two factors: (1) the patient's immune response, and (2) sufficiency plus efficiency of the regulator(s). Concerning the first, the present research introduces a framework based on different types of immune responses to COVID-19 along with known disease examples,and how this relatesto varying clinical outcomes and treatment needs for COVID-19 patients. About the second factor of 'regulator(s)', part 1 of the manuscript described in depth the regulatory role of progesterone in COVID-19.The present study investigates the two immunity patterns and the status of the regulatory hormone progesterone with respect to the two established demographic risk factors for high-severity COVID-19: male sex, and old age. The study evaluates the status of progesterone as a credible participant of immune regulationand dysregulation. It duly relates the immunity patterns to clinical outcomes and evinces indications for clinical use of progesterone in COVID-19.It proposes a clear answer to the question: why are males and old patients most likely to have critical illness due to COVID-19? The study highlights clinical domains for the use of progesterone in COVID-19. Part 2 of this research introducing the concept of immunity patterns and immunity grading. These concepts herewith provided for the clinical course of COVID-19 also applies to other hyperinflammatory conditions. Possible clinical applications of progesterone to treat critically ill COVID-19 patients will open an avenue for hormonal treatments of infections and other immune-related diseases.
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Аbstrасt This study is to estimаte in-hоsрitаl mоrtаlity in severe асute resрirаtоry syndrоme соrоnаvirus 2 (SАRS-СоV-2) раtients strаtified by Vitamin-D (Vit-D) levels. Раtients were strаtified ассоrding tо by serum 25-Hydroxy-Vitamin D (25(OH)Vit-D) levels intо twо grоuрs, i.e., 25(OH)Vit-D less thаn 40 nmol/L аnd 25(OH)Vit-D greаter thаn 40 nmol/L. А tоtаl оf 231 раtients were inсluded. Оf these, 120 (50.2%) оf the раtients hаd 25(OH)Vit-D levels greаter thаn 40 nmol/L. The meаn аge wаs 49 ± 17 yeаrs, аnd 67% оf the раtients were mаles. The mediаn length оf оverаll hоsрitаl stаy wаs 18 [6; 53] dаys. The remаining 119 (49.8%) раtients hаd а 25(OH)Vit-D less thаn 40 nmol/L. Vitamin D levels were seen deficient in 63% of patients, insufficient in 25% and normal in 12%. Оverаll mоrtаlity wаs 17 раtients (7.1%) but statistically not signifiсаnt among the grоuрs (p=0.986). The Kарlаn-Meier survivаl аnаlysis shоwed no significance based on an alpha of 0.05, LL = 0.36, df = 1, p = 0.548, indicating Vitamin_D_Levels was not able to adequately predict the hazard of Mortality. In this study, serum 25(OH)Vit-D levels were found have no significance in-terms of predicting the in-hоsрitаl mortality in SАRS-СоV-2 раtients. This article is protected by copyright. All rights reserved.
Article
Background It is known that Vitamin D can increase the body’s immunity against some viral infections. Many people around the world have vitamin D deficiency and, therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D on immunity and recovery from viral infections, especially novel Coronavirus disease (COVID-19) is reviewed. Methods The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE) and Medical and Health Education (Medrix) were searched. Results Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can raise cellular immunity, reduce cytokine storm and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect. Conclusion Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection.
Article
We discuss the quality of the article evidence on the association between vitamin D deficiency and COVID-19, as well as updating the statistics in response to the letter to the editor regarding the same paper. Our review included 22 studies with data available in 23 articles. Using crude OR data, we observed that the chance of hospitalization was 2.16 (CI 95% = 1.42 − 2.89;) for vitamin-deficient individuals compared to non-deficient ones. However, when using the adjusted OR, it was possible to obtain a chance of 1.78 (CI 95% = 1.36-2.20). For the outcome vitamin D deficiency and death in patients with COVID-19 infection the crude association value was 1.38 (OR =1.38; CI 95% = 1.08 − 1.68) and the adjusted OR with the two studies was 1.08 (CI 95% = 0.82- 1.34). This new analyzes don't substantially alter our results. Vitamin D remains associated with severity COVID-19.
Article
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This study is done to estimаte in-hоsрitаl mоrtаlity in раtients with severe асute resрirаtоry syndrоme соrоnаvirus 2 (SАRS-СоV-2) strаtified by Vitamin-D (Vit-D) levels. Раtients were strаtified ассоrding tо by serum 25-hydroxy-vitamin D (25(OH)Vit-D) levels intо twо grоuрs, that is, 25(OH)Vit-D less thаn 40 nmol/L аnd 25(OH)Vit-D greаter thаn 40 nmol/L. А tоtаl оf 231 раtients were inсluded. Оf these, 120 (50.2%) оf the раtients hаd 25(OH)Vit-D levels greаter thаn 40 nmol/L. The meаn аge wаs 49 ± 17 yeаrs, аnd 67% оf the раtients were mаles. The mediаn length оf оverаll hоsрitаl stаy wаs 18 [6; 53] dаys. The remаining 119 (49.8%) раtients hаd а 25(OH)Vit-D less thаn 40 nmol/L. Vitamin D levels were seen as deficient in 63% of patients, insufficient in 25% and normal in 12%. Оverаll mоrtаlity wаs 17 раtients (7.1%) but statistically not signifiсаnt among the grоuрs (p = 0.986). The Kарlаn–Meier survivаl аnаlysis shоwed no significance based on an alpha of 0.05, LL = 0.36, df = 1, p = 0.548, indicating Vitamin_D_Levels was not able to adequately predict the hazard of Mortality. In this study, serum 25(OH)Vit-D levels were found have no significance in terms of predicting the in-hоsрitаl mortality in раtients with SАRS-СоV-2.
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LINKED CONTENT This article is linked to Al‐Ani et al and Garg et al papers. To view these articles, visit https://doi.org/10.1111/apt.15779 and https://doi.org/10.1111/apt.15796.
Preprint
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Background/Aims: WHO declared SARS-Cov-2 a global pandemic. The aims of this paper are to assess if there is any association between mean levels of vitamin D in various countries and cases respectively mortality caused by COVID-19. Methods: We have identified the mean levels of vitamin D for 20 Europeans Countries for which we have also got the data regarding the morbidity and mortality caused by COVID-19. Results: The mean level of vitamin D (average 56mmol/L, STDEV 10.61) in each country was strongly associated with the number of cases/1M (mean 295.95, STDEV 298.73 p=0.004, respectively with the mortality/1M (mean 5.96, STDEV 15.13, p < 0.00001). Discussion: Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of population for COVID-19. Conclusions: We believe, that we can advise Vitamin D supplementation to protect against SARS-CoV2 infection.
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The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
Article
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Maintaining a normal healthy immune defense system lowers the incidence and/or the severity of symptoms and/or the duration of common cold (CC). Physical barriers and innate and adaptive immunity have been involved during a CC episode. Vitamins C and D, zinc, and Echinacea have evidence-based efficacy on these immune system barriers. This review includes 82 eligible studies to consider the preventive role of these nutrients in immune clusters and in CC to provide advice on dosage and assumption of these nutrients. Regarding vitamin C, regular supplementation (1 to 2 g/day) has shown that vitamin C reduces the duration (in adults by 8%, in children by 14%) and the severity of CC. Considering zinc, the supplementation may shorten the duration of colds by approximately 33%. CC patients may be instructed to try zinc within 24 hours of onset of symptoms. As for vitamin D, the supplementation protected against CC overall, considering baseline levels and age. Patients with vitamin D deficiency and those not receiving bolus doses experienced the most benefit. Regarding Echinacea , prophylactic treatment with this extract (2400 mg/day) over 4 months appeared to be beneficial for preventing/treating CC. In conclusion, the current evidence of efficacy for zinc, vitamins D and C, and Echinacea is so interesting that CC patients may be encouraged to try them for preventing/treating their colds, although further studies are needed on this topic.
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Higher vitamin D concentrations have been proposed as a protective 'seasonal stimulus' against influenza, and there are suggestions for associations with other aspects of respiratory health. The aim of the present study was to investigate the relationship of current vitamin D status (measured by 25-hydroxyvitamin D, 25(OH)D) with respiratory infections and lung function. We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D, lung function (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)) and respiratory infections available from the age of 45 years. In this population, the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations. Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection (95 % CI 3, 11 %) after adjustment for adiposity, lifestyle and socio-economic factors. For FEV1 and FVC, each 10 nmol/l increase in 25(OH)D was associated with 8 (95 % CI 3, 13) ml and 13 (95 % CI 7, 20) ml higher volume, respectively, after controlling for covariates. Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness. In conclusion, vitamin D status had a linear relationship with respiratory infections and lung function. Randomised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms.
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Twenty-eight patients with anaerobic pleuropulmonary infections were treated with clindamycin alone or clindamycin with gentamicin. Sixteen of the patients presented with pneumonitis, nine with necrotizing pneumonia, and three with lung abscesses. The average length of treatment was 13.8 days, and the duration of temperature after initiation of therapy was 3.1 days. The predominant isolates were anaerobic gram-positive cocci (23 isolates), Bacteroides melaninogenicus (14), Bacteroides fragilis (9), and Fusobacterium nucleatum (11). The most frequent aerobic isolates were alpha-hemolytic streptococci (12), Diplococcus pneumoniae (12), Pseudomonas aeruginosa (9), Klebsiella pneumoniae (7), group A beta-hemolytic streptococci (5), Staphylococcus aureus (9), and Escherichia coli (6). All patients responded to the therapy and were cured of the infection. There were no side effects observed from the administration of clindamycin. None of the patients developed any blood dyscrasia, liver damage, diarrhea, or colitis. Clindamycin appears to be effective in the treatment of mixed aerobic and anaerobic pleuropulmonary infections in children, alone or with an aminoglycoside when indicated.
Preprint
The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
Article
Background: Ulcerative Colitis (UC) is a chronic recurrent inflammation of the colon. It has been proposed that the UC pathogenesis may be related to vitamin D deficiency and/or vitamin D administration in UC patients may have an ameliorating effect on the intestinal inflammation. The aim of this study was to assess the effect of vitamin D on the serum levels of immune cytokines in UC patients. Methods: In this double-blind randomized controlled trial 90 mild to moderate UC patients were assigned to get either a single muscular injection of 7.5 mg vitamin D3 or 1 ml normal saline as placebo. Three months later serum levels of IL-4, IL-10, IL-12p70, IFN-γ, and TNF-α were measured. Two group variables were compared using independent t-test and analysis of covariance (ANCOVA). Results: There was a significant increase in vitamin D only in the vitamin D group. Compared to placebo, vitamin D had significant decreasing effects on serum TNF-α, IFN-γ, and IL12p70 levels, but it had no significant effect on serum levels of IL4 and IL10. Conclusion: Vitamin D seems to inhibit Th1 immune responses, and have no effect on Th2 responses. The findings of this study support several in vitro studies, which suggest a therapeutic immunomodulatory potential of vitamin D. This article is protected by copyright. All rights reserved.
Article
We hypothesized that deficiency in 25-hydroxyvitamin D before hospital admission would be associated with all-cause mortality in the critically ill. Multicenter observational study of patients treated in medical and surgical intensive care units. A total of 209 medical and surgical intensive care beds in two teaching hospitals in Boston, MA. A total of 2399 patients, age ≥ 18 yrs, in whom 25-hydroxyvitamin D was measured before hospitalization between 1998 and 2009. None. Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (16-29 ng/mL), and sufficiency (≥ 30 ng/mL). Logistic regression examined death by days 30, 90, and 365 post-intensive care unit admission, in-hospital mortality, and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.69 (95% confidence interval of 1.28-2.23, p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following intensive care unit admission following multivariable adjustment (adjusted odds ratio of 1.69, 95% confidence interval of 1.26-2.26, p < .0001). At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D insufficiency have an odds ratio of 1.32 (95% confidence interval of 1.02-1.72, p = .036) and an adjusted odds ratio of 1.36 (95% confidence interval of 1.03-1.79, p = .029) relative to patients with 25-hydroxyvitamin D sufficiency. Results were similar at 90 and 365 days following intensive care unit admission and for in-hospital mortality. In a subgroup analysis of patients who had blood cultures drawn (n = 1160), 25-hydroxyvitamin D deficiency was associated with increased risk of blood culture positivity. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for blood culture positivity of 1.64 (95% confidence interval of 1.05-2.55, p = .03) relative to patients with 25-hydroxyvitamin D sufficiency, which remains significant following multivariable adjustment (odds ratio of 1.58, 95% confidence interval of 1.01-2.49, p = .048). Deficiency of 25-hydroxyvitamin D before hospital admission is a significant predictor of short- and long-term all-cause patient mortality and blood culture positivity in a critically ill patient population.
Article
Vitamin D and the vitamin D receptor (VDR) have been shown to be important regulators of the immune system. In particular, vitamin D and VDR deficiency exacerbates experimental autoimmune diseases such as inflammatory bowel disease (IBD). IBD develops due to an immune-mediated attack by pathogenic T-cells that overproduce IL-17 and IFN-gamma and a few regulatory cells. VDR knockout mice have twice as many T-cells making IL-17 and IFN-gamma than wild-type mice. In addition, vitamin D and the VDR are required for normal numbers of regulatory T-cells (iNKT and CD8alphaalpha) that have been shown to suppress experimental IBD. In the absence of vitamin D and the VDR, autoimmunity occurs in the gastrointestinal tract due to increased numbers of IL-17 and IFN-gamma secreting T-cells and a concomitant reduction in regulatory T-cells.
Global epidemic of coronavirus--COVID-19: What we can do to minimize risks
  • S J Wimalawansa