cord-004297-rm0zbgfm	2020	Because of the high dropout rate (42%), we did not include this trial in our calculations, but we overlay the findings in Fig. 4 iv intravenous, po per oral, RoM ratio of means [22] : e.g., for the Bjordahl trial [11] , RoM = 0.86, based on 28.8/33.6, and RoM = 0.86 indicates that ventilation time in the vitamin C group was 14% shorter than in the placebo group (RoM) [22] . In a meta-regression analysis, we found that the heterogeneity between the trials was explained by the length of mechanical ventilation in the untreated control group (Fig. 4) . Thus, the statistically significant benefit observed in each of these three trials might be explained by the long ventilation time in the control groups, indicating greater severity of illness in the patients, rather than by the addition of vitamin E to the intervention. Although our meta-regression analysis by the ventilation time in the control group explains the heterogeneity in the published trials, it seems evident that other variables influence the effects of vitamin C.
cord-005428-pm7ihh9t	2020	As there is no evidence that increasing the recommended daily dose of vitamin D supplementation up to 50 μg (2000 IU) would cause severe side effects in the general population, and considering that 20 μg (800 IU) is the lowest dose consistently associated with a bone benefit, it seems reasonable to recommend a daily dose of 20-50 μg (800-2000 IU) (levels 2-4 evidence, grades B-D recommendation) [39] . However, several studies in recent years have highlighted that women are at high risk for vitamin D deficiency, and this is associated with adverse pregnancy outcomes, including preeclampsia and gestational diabetes [76] [77] [78] [79] [80] . VIOLET randomized patients with 25 (OH)D levels below 50 nmol/L (or 20 ng/ml) "at risk for ARDS" to one single high dose of vitamin D3 (540,000 IU), and evaluated its effect on the primary outcome: 90-day mortality.
cord-006636-xgikbdns	1964	
cord-010443-4jblod8j	2020	In critical illness, NF-κB-driven systemic inflammation, also known as a "cytokine storm" (14) , activates a multi-system response that includes at least three major domains: (i) the stress system composed by the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus-norepinephrine/sympathetic nervous system activated to provide sufficient energy and hemodynamic stability to overcome the initial phase of critical illness (15) ; (ii) the acute-phase reaction (APR), which has several adaptive functions, including increasing the production of procoagulant factors in preparation for possible tissue damage (16) ; and (iii) the tissue defense response (TDR) of the target organs [ Figure 1 ; (11, 17) ]. In patients with septic shock (170, 171) or ARDS (172, 173) , prolonged glucocorticoid (hydrocortisone or methylprednisolone) treatment resulted in the following: (i) increased plasma activated protein C levels (173); (ii) reduction in markers of endothelial injury such as sICAM-1 (35); (iii) rapid and consistent improvement in capillary perfusion, independently of the cortisol response to ACTH (170) ; and (iv) improvement in alveolar-capillary (172) and renal (171) endothelial permeability.
cord-013342-vx3eor43	2020	NRs, including the vitamin D receptor (VDR), estrogen receptor (ER), estrogen-related receptors (ERRs), and peroxisome proliferator-activated receptors (PPARs) have been shown to play critical functions in the regulation of autophagy-mediated host defensive immune responses during infection. HepG2, Huh7 cells ↑ Lipid metabolism Upregulation of C19orf80 expression, which is involved in lipid metabolism through breakdown of lipid droplets [208] Mice model of hepatocarcinogenesis, HepG2 cells ↑ Inhibition of hepatic DNA damage, inflammation, and carcinogenesis Induction of hepatic PINK1 expression, which ubiquitinates HBx protein to trigger mitophagy [209] CEBPB, CCAAT/enhancer-binding protein beta; TFEB, transcription factor EB; TFE3, transcription factor E3; LAMP1, lysosomal-associated membrane protein 1; IL, interleukin; LKB1, liver kinase B1; AMPK, AMP-activated protein kinase; DRAM2, DNA-damage regulated autophagy modulator; PML, promyelocytic leukemia; ATRA, all-trans-retinoic acid; HPAIV, highly pathogenic avian influenza virus; APL, acute promyelocytic leukemia; MI/R, myocardial ischemia/reperfusion; HL, Hodgkin lymphoma; RPE, retinal pigment epithelium cells; NRF2, nuclear factor erythroid 2-related factor 2; HBV, hepatitis B virus; DDA, dendrogenin A; Nur77, nerve growth factor IB; Nor1, neuron-derived orphan receptor 1; T3, triiodothyronine; PINK1, PTEN-induced kinase 1.
cord-016009-qa7bcsbu	2019	Disease that restricts airflow through either inflammation of the lining of the bronchial tubes or destruction of alveoli Increased risk of emphysema if genetic variant of alpha-1 antitrypsin deficiency and smoking or exposed to high levels of air pollution [11] Bronchiectasis A disorder of the airways that leads to airway dilation and destruction, chronic sputum production, and a tendency toward recurrent infection [39] Bronchiolitis Airway injury that can be caused by infections, irritants, toxic fumes, drug exposures, pneumonitis (typically viral), organ transplants, connective tissue disorders, vasculitis, or other insults [40] Dyspnea Shortness of breath or difficulty breathing [11] Emphysema Thinning and destruction of the alveoli, resulting in decreased oxygen transfer into the bloodstream and shortness of breath.
cord-016130-5q9ufu28	2010	
cord-017428-euzvhtax	2012	A recent intervention trial with high-dose supplementation in COPD was only able to reduce exacerbation frequency in the subgroup of patients with lowest baseline vitamin D levels. Besides the well-known effect of vitamin D de fi ciency on bone loss in adults, accumulating evidence also links a low vitamin D nutritional status to highly prevalent chronic illnesses, including cancers, autoimmune diseases, infectious and cardiovascular diseases [1] [2] [3] . This chapter aims to discuss the prevalence and determinants of vitamin D de fi ciency in COPD, the wellknown effect of vitamin D in the development and treatment of COPD-associated osteoporosis and its potential role in the uncontrolled in fl ammatory cascade and systemic consequences of the disease. The fact that the majority of COPD patients are of older age, have many common risk factors for osteoporosis and are more likely to be de fi cient in vitamin D supports standard supplementation, especially at the more severe stages of disease.
cord-017656-lqrkwlnb	2019	Inflammatory cells are markedly increased in BAL fluid, providing the immunological evidences that daily supplementation of high-dose vitamin C can prevent influenza infection and that, in extreme case, it can save the life. One is that the common cold comes from an imbalance between the human defense system and the normal viral flora, which normally reside at the initiation part of the respiratory system such as the nasal cavity and nasal or oral pharynx so that they usually do not induce new immunity against the normal floral virus. Unlike the common cold, which is usually not infected by a foreign pathogen but is just a kind of battle between the body defense system and the normal flora of viruses residing in the upper respiratory system, the flu is a disease caused by an influenza virus infection.
cord-018204-rqp4huk3	2013	If vitamin D intervention currently under study in several clinical trials is proven successful, then implementation of new fortification practices, revised guidelines for healthy sun exposure and public health programs for vitamin D supplementation of pregnant/lactating women and their infants may be effective strategies to aide in preventing neonates and children under five from developing pneumonia. If vitamin D intervention currently under study in the clinical trials described in this chapter is proven successful, then implementation of new fortification practices, revised guidelines for healthy sun exposure and public health programs for vitamin D supplementation of pregnant/lactating women and their infants may be effective strategies to aid in preventing neonates and children under five from developing respiratory infections.
cord-020493-ddo3a7wq	2005	Wenn abzusehen ist, dass postoperativ über einen Zeitraum von mehr als 3 Tagen eine teil-oder vollparenterale Ernährung erfolgen muss, sollten zusätzlich zu den Kohlenhydraten Proteine und Lipide supplementiert werden ( Kap. 7.2). Obwohl Wachstumshormon das potenteste Mittel zur Stimulation der Proteinsynthese mit dem Effekt einer verbesserten Wundheilung, verringerten Infektionsrate und entsprechender Verkürzung der Behandlungsdauer ist, zeigten Studien bisher jedoch eine erhöhte Mortalität nach Behandlung mit r-HGH bei akuter Katabolie, so dass sich dieser zunächst viel versprechende Therapieansatz zur Unterdrückung der Eiweißkatabolie nicht durchsetzen wird. ▬ Die Supplementation von Vitamin K sollte bei allen Frühgeborenen <35 Schwangerschaftswoche (SSW) und kranken Reifgeborenen wegen der unklaren enteralen Resorption bei den ersten beiden Gaben als subkutane, intramuskuläre oder intravenöse Gabe erfolgen (Greer 1995 ▬ Bei gesunden reifen Neugeborenen bringt eine intramuskuläre Gabe keine Vorteile gegenüber einer oralen Supplementation (Baker et al.
cord-026028-qj290zu6	2008	Früher behauptete Zusammenhänge zwischen mütterlicher Therapie und erhöhtem Risiko für eine nekrotisierende Enterokolitis (NEC) beim Neugeborenen wurden unter anderem in einer Studie an 59 Schwangeren widerlegt, die Theophyllin als Tokolytikum oder zur Surfactantbildung vor Woche 34 erhalten hatten (Zanardo 1996) . B. für das Anticholinergikum Glycopyrronium) offenbar gut vom Fetus vertragen (Ure 1999 Mesalazin wird sehr häufig in der Schwangerschaft verordnet, ohne dass sich bisher Hinweise auf teratogene Wirkungen ergeben haben (Habel 1993 , Diav-Citrin 1998 , Marteau 1998 Ursodeoxycholsäure wirkt bei hepatozellulären Schäden, die durch Gallensäuren induziert sind, also vor allem bei cholestatischen Erkrankungen, wie der primär biliären Zirrhose. Kein Anhalt für ein erhöhtes Fehlbildungsrisiko fand sich hingegen in anderen prospektiven Kohortenstudien und retrospektiven Untersuchungen mit über 600 Frauen, die in den Monaten vor oder während einer Schwangerschaft meist wegen Vaginalmykose niedrig dosiert (150 mg/Tag) mit Fluconazol behandelten wurden (Jick 1999 , Sørensen 1999 , Campomori 1997 , Mastroiacovo 1996 , Inman 1994 .
cord-030992-ed0h045d	2020	Deficiencies of micronutrients, especially vitamins A, B complex, C, and D, zinc, iron, and selenium, are common among vulnerable populations in general and among COVID-19 patients in particular and could plausibly increase the risk of mortality. Vitamins A, B complex, C, D, and E and many trace elements, such as iron, zinc, selenium, magnesium, and copper, have been shown to elicit immune-boosting properties, [14] [15] [16] and thus deficiencies of these micronutrients could be detrimental to immune function in viral infections. 73, 74 Zhang and Liu 12 suggested supplementation with vitamin C to reduce the incidence of severe lower respiratory tract infections, such as pneumonia, and as a treatment option for COVID-19. In light of these findings on the role of PUFA derivatives in mediating immune function, omega-3 PUFA metabolites like protectin D1 may be useful as supportive dietary therapy for prevention and treatment of flu-like viral infections, including COVID-19.
cord-032544-2yrqjw1o	2020	title: Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial DISCUSSION: Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy TRIAL REGISTRATION: ClinicalTrials.gov NCT02870829. [27] A recent randomized trial reporting 1-year outcome of vitamin K2 supplementation in hemodialysis patients found no effect on aortic calcification despite reduction in dp-ucMGP. The proposed "Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K" (Trevasc-HDK) study is therefore timely. Our trial is important even if the study is negative as we will have more insight into the baseline level and role of vitamin Kin Asian patients as well as provide us with the magnitude and progression of calcification in our multiethnic HD population. The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial
cord-034441-30pw419v	2020	In a clinical study, supplementation of 4000 IU / day vitamin D has also been reported to reduce Dengue virus infection severity (12) . When another study of 212 patients with proven SARS-CoV-2 infection was examined, serum 25 (OH) D level was the lowest in clinically severe cases, whereas it was highest in mild cases. When all the results in the study are evaluated, the rise in serum 25 (OH) D levels in the COVID-19 patients suggests that it may improve clinical course or alleviate clinical outcomes even in severe cases. Among the causes of this clinical diversity in the course and mortality rates of the COVID-19 cases, it is an important to remind that vitamin D deficiency can also be underlying comorbidity in the patients. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (COVID-2019).
cord-103451-h7986yl9	2020	There was little evidence for vitamin D levels causally influencing the risk of AD (odds ratio per SD change in log-transformed 25-OHD levels = 1.233, 95% CI 0.927 to 1.639, P-value =0.150), a finding in keeping with the 2017 analysis which found an effect size of 1.12, (95% CI 0.92 to1.37, P-value =0.270) (Manousaki et al. To investigate the causal effect of genetically predicted vitamin D levels upon AD risk, a genetic instrument for 25-OHD levels was derived from SNPs reported to be most strongly associated (Pvalue < 5x10 -8 ) in the most current GWA study by Manousaki and colleagues (N=443,734) (Manousaki et al. Our genetic instrument for vitamin D levels was used to assess the causal effect upon AD risk using summary GWAS data from the most recent AD GWAS meta-analysis (Paternoster et al.
cord-254646-psolkrom	2020	This review will briefly summarize fundamental, well-established aspects of vitamin D and human health and then will also discuss (a) some of the most recent work related to vitamin D and non-skeletal-associated health issues; (b) the complexity of establishing meaningful vitamin D measurement metrics and assessing vitamin D status; c)decisionmaking for obtaining vitamin D through diet, supplements, or sun exposure; (d) the impact of skin type, pigmentation, and sunscreen on vitamin D levels; and (e) evidence for a potential influence of vitamin D on the mortality and morbidity of COVID-19 through modulation of the pro-inflammatory cytokine response and respiratory response to the virus. To some extent, this is because relevant factors vary: vitamin D food fortification regulations, the strength of ambient ultraviolet radiation (UVR), levels of smog, culture and ethnicity, skin phototype, chronological age, and ease and accuracy of specific clinical laboratory measurements.
cord-255233-rvgj6pvk	2020	Methods: Patients were invited to participate following assessment and treatment at the Westmead Centre of Oral Health Periodontic Clinic, regardless of current disease stage or treatment. Conclusion: Although a small study, this rate of vitamin C deficiency in the periodontal clinic is clinically important and correlations with disease severity and CRP suggests biological importance. Vitamin C deficiency is more common in smokers, the elderly and people of lower socio-economic status, potentially putting those groups at increased risk of periodontal diseases [24, 25] . Patients were eligible to participate in this study if they were an adult attending the Westmead Centre of Oral Health (WCOH) Periodontic Clinic. Patients were eligible to participate in this study if they were an adult attending the Westmead Centre of Oral Health (WCOH) Periodontic Clinic. This study reports that a significant proportion of patients attending the Periodontics Clinic at the Westmead Centre of Oral Health have vitamin C deficiency.
cord-257595-l8bsoqbx	2020	BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. This study is the first to document a statistically significant correlation between a country''s latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Because of the positive correlation between sunlight UV radiation and healthy Vitamin D levels in the body, and reported positive correlation between Vitamin D deficiency and fatality rates to COVID-19, the present study examined the relationship between a country''s proximity to the equator and its death rates from the current pandemic.
cord-262773-mfta0emi	2020	title: Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials Design: We conducted a systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. We previously meta-analysed individual participant data from 25 RCTs and showed a protective overall effect that was stronger in those with lower baseline 25(OH)D levels, and in trials where vitamin D was administered daily or weekly rather than in more widely spaced bolus doses. Randomised, double-blind, trials of supplementation with vitamin D 3 , vitamin D 2 or 25(OH)D of any duration, with a placebo or low-dose vitamin D control, were eligible for inclusion if they had been approved by a Research Ethics Committee and if data on incidence of ARI were collected prospectively and pre-specified as an efficacy outcome.
cord-263749-bbhh5xb1	2020	We divide the reviewed interventions in: 1) lifestyle related (exercise, >7 hours sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod) and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, i.e.). The complete mechanism by which zinc could decrease the number or severity of viral infectious 308 processes in general and of COVID-19 in particular is not exactly understood yet; however, effects have 309 been observed on the binding of the viral agent to the mucosa and on its replication, as well as on the 310 regulation of the inflammatory process;(73) enhanced benefits have been hypothesized when co-311 administered with other medications such as (hydroxy)chloroquine that could function as a ionophore, 312 facilitating the entrance of zinc into the cells.(74) The human body''s ability to store zinc is known to be 313 low; its deficiency compromises the immune system, as has been evidenced occasionally by thymic 314 atrophy, lymphopenia and altered lymphocyte responses.
cord-265340-hc9003dj	2020	title: Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study We hypothesized that the mean plasma level of 25(OH)D would be significantly lower and, accordingly, the rate of suboptimal plasma 25(OH)D would be significantly higher, among persons testing positive for COVID-19 infection, and among persons subsequently hospitalized, in a large population-based data study. The main finding of this study was the low plasma 25(OH)D level association with COVID-19 hospitalization risks, for patients tested positively for COVID-19, after adjusting for age, gender, SES and chronic, mental and physical disorders. To conclude, our study found that suboptimal plasma vitamin D levels may be a potential risk factor for COVID-19 infection, particularly, for the high hospitalization risks, independent of demographic characteristics and medical conditions.
cord-269161-6nsvup68	2020	We read with great interest the article by Li et al., where authors have reviewed many therapeutic strategies for critically ill patients with coronavirus disease (COVID-19) [1] . Though authors have not mentioned, another important supplementary adjunct to treat these critically ill patients in intensive care unit is various vitamins. A large systematic review and meta-analysis including 11,321 patients has also shown that vitamin D supplementation is effective against acute respiratory tract infection [6] . Therefore, these vitamins have shown to protect against the acute viral infections and should be the part of adjunctive therapy in critically ill COVID-19 patients. Therapeutic strategies for critically ill patients with COVID-19 The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
cord-271968-92p8dmha	2020	The higher protein content in bovine milk can also negatively affect the calcium balance; the final result is that the high consumption of dairy products, together with other dietary sources of phosphorus, can increase the risk of osteoporosis [32] . Even if donkey milk represents a niche product, its use is recommended for consumers at risk of nutritional deficiencies, such as children and/or elderly; in these patients, donkey milk could help prevent lack of vitamin D [58] . The results obtained in this clinical trial demonstrated that fortified soft plain cheese consumed by elderly women with vitamin D deficiency can reduce bone resorption, positively affecting Ca and protein metabolism, analyzing the decrease in PTH and increase in IGF-I, respectively [69] . Vitamin D fortification of basic foods such as dairy and flour products can increase serum 25(OH)D concentrations, reducing the risk of osteoporosis.
cord-276130-wjnwpn8f	2020	Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. Inclusion/exclusion criteria Reviews were included if they were described as "systematic" and exhibited methods consistent with systematic reviews (i.e., defined clinical question, detailed search protocol, etc.) and reported on human prospective intervention trials sampling adults and/or children with reported ARTI. Despite several positive systematic reviews and meta-analyses, the available experimental evidence related to the effects of vitamin D on acute respiratory tract infection (ARTI) is plagued with heterogeneity and mixed quality, and therefore is insufficient to recommend vitamin D supplementation to the general population as a protective agent against ARTI. Effect of Vitamin D3 Supplementation on Respiratory Tract Infections in Healthy Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
cord-276483-4yp4beuh	2020	Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis. Years of hyperinsulinaemia that would manifest overt pathologies such as obesity, CVD, hypertension and cancer would come with an already heavy-risk burden list, which includes: increased haemoglobin glycation damage, intracellular haem-oxidation with reduced antioxidative capacity, increased haem-oxygenase haem catabolism thus producing increased endogenous carbon monoxide production, leading to increased risk of DVT and subsequent PE and decreased mitochondrial vitamin D hydroxylase activation.
cord-276942-dk1rk908	2020	In vitro culture of human fetal and adult alveolar type-II cells with 1,25-dihydroxyvitamin D increased VDR and the expression of surfactantassociated protein B, a lipid-associated protein of the pulmonary surfactant [23] , indicating the potential of vitamin D to reduce surface tension in COVID-19. In line with our objective to improve vitamin D status and its associated outcomes in patients with COVID-19, studies have shown treatment with high dose of 250,000-500,000 IU vitamin D to be safe in mechanically ventilated, critically ill patients and was associated with decreased hospital length of stay, improved ability of the blood to carry oxygen and increased hemoglobin levels [24, 25] . High prevalence of vitamin D deficiency in elderly, smokers, patients with chronic diseases, and excess uptake by adipose tissue in obesity make investigations of its role as a therapeutic agent in COVID-19 conceivable.
cord-284193-qslc2wry	2020	It can induce ACE2/Ang‐(1‐7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang‐(1‐7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin-converting enzyme 2 (ACE2), a part of the reninangiotensin system (RAS), serves as the major entry point into cells for some coronaviruses such as HCoV-NL63, SARS-CoV and SARS-CoV-2 that cause SARS and COVID-19, respectively. 71, 72 Although it is more likely that any protective effect of vitamin D against COVID-19 is related to suppression of cytokine response and reduced severity/risk for ARDS, there is also evidence from a meta-analysis that regular oral vitamin D2/D3 intake (in doses up to 2000 IU/day) is safe and protective against acute respiratory tract infection, especially in subjects with vitamin D deficiency.
cord-284760-i1lspg8i	2018	In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats. Thus, this study aimed to investigate hepatoprotective activities of nicotinamide, vitamin B2, and vitamin C, separately or in combination, against thioacetamide-induced liver damage, hyperlipidemia and oxidative stress in rats. In the present data, TAA administration resulted in a significant reduction in the Table 3 Effect of Nicotinamide, Vitamin b2 and Vitamin C on hepatic MDA (nmol/mg), GSH (μmol/g tissue), catalase (U/g tissue), SOD (U/g tissue), NO (nmol/g,Hydroxyproline (Ug/g tissue) and plasma TNF-α (Pg/ml) plasma levels of a total protein that might be indicative of injury in the hepatocytes and excessive destruction of proteins including antioxidant enzymes and cellular reducing powers including SH-protein bond production or alterations in RNA sequences in the target tissues.
cord-285641-y5ianyqi	2020	Studies done by the authors in the villages of Medak district, of the South Indian state of Telangana, show remarkable improvement in the knowledge of food, nutrition, hygiene and health of mothers with children under 3 years of age, with education–behavioural change communication. These findings are akin to those of the National Nutrition Monitoring Bureau surveys in India, which show that the cereal-based Indian diets are deficient in the consumption of micronutrient-rich foods like vegetables, fruits, legumes and animal products [3] . A recent study from the National Institute of Nutrition, Hyderabad, India, shows a high prevalence of vitamin deficiencies, particularly, vitamins A, B2, B6, B12, folic acid and vitamin D, assessed by subclinical status (blood values) and dietary intakes, in an apparently healthy urban adult population [4] . Hellen Keller International has supported an extensive programme of improved homestead gardens and backyard poultry in Bangladesh, Cambodia, Nepal and Philippines to increase the production and household availability of micronutrient-dense vegetables and fruits and eggs.
cord-286923-o4fj8kx0	2020	The immunological changes predominantly inclining to anti-inflammatory state, which is augmented by placental hormones'' immune modulating action, looks against with COVID-19 inflammatory reaction leading to cytokine storm and multiple organ failure. As discussed hereunder, accumulating evidence from other infections and autoimmune diseases shows that immune modulating hormones, cytokines and other anti-inflammatory endogenous ligands are determinant factors in reducing the severity of several diseases during pregnancy; which could also be the most plausible explanation for the less severity and mortality of Covid-19 in pregnant women. Despite serious concern for patients with autoimmune disease, taking their immune suppression and medications, at least 110 individuals (79% females) with rheumatoid arthritis and got infected with SARS CoV-2 (from six continents) were not as such at higher risk of mortality, probably as they were on anti-inflammatory medication; only 6(5%) persons died of COVID-19 [89] .
cord-286960-uz34fjyp	2020	This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. Some recent reviews hypothesized that vitamin D insufficiency may compromise respiratory immune function, increasing the risk of COVID-19 severity and mortality [12, 13] . There are also some retrospective studies that determined the correlation of vitamin D levels with COVID-19 severity and mortality [14] [15] [16] [17] [18] [19] [20] [21] [22] The recent outbreak and fast spreading of SARS-CoV-2 are a global health threat with an unstable outcome worldwide. Another study included 25 randomized controlled trials, with 10,933 participants in total from 14 different countries indicated the beneficial effects of vitamin D supplementation in reducing the risk of at least one acute respiratory tract infection [59] .
cord-290428-zrlqzbss	2020	Since to date there is no vaccine or evidence-based treatment for COVID-19, the optimization of nutrient intake through well-balanced meals and the use of good hygiene practices in food selection, preparation, and conservation is probably the most effective approach for managing the continuous risk of viral infection. There is no evidence that COVID-19 is spread through eating or touching raw fruits or vegetables; Prior to consumption, fresh fruits and vegetables should be washed or scrubbed under cold, running, potable tap water; While there are no special precautions for storing food, handwashing after putting away purchased food and before preparing food is recommended; Hands should be washed before and after food containers are washed EUFIC (2020) 19 Appropriate intakes of copper, folate, iron, selenium, zinc, and vitamins A, B 6 , B 12 , C, and D play an important role in the immune system; In general, these nutrients should be obtained through foods Supplements can be used to add nutrients to the diet in individuals who have specific challenges in meeting dietary requirements
cord-290592-c9bsielo	2020	
cord-291340-8gj0ofmp	2020	In a Cochrane review [26] , and other studies [27] probiotics were shown to decrease upper respiratory infections through their effect on the gut lung axis [28] Role of several other nutrients and food constituents like Vitamins(E, B) Carotenoids, minerals (Fe, Zn, Mg, Cu, Se), and polyphenols in immunity have been suggested because of their effects on inflammatory cascade, antioxidant activities and effects on nitrous oxide signalling pathways [25] (Table 1) . Controlled trials also show reduced complications when serum albumin level is adequate [44] .In a recent scoping review(four studies in patients with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 in patients with ventilator-associated pneumonia), intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulphate, and oral and parenteral glutamine were given as interventions.
cord-294800-akr4f5p8	2020	
cord-295414-v10454ns	2020	1 Furthermore, research by Alipio and colleagues 2 , in a retrospective study, provides evidence of an association between vitamin D deficiency and adverse outcome in patients with COVID-19. Among patients with vitamin D deficiency in the COVID-19-positive group, there was a higher average peak in D-dimer level (1914.00 μgFEU/L vs 1268.00 μgFEU/L) (p=0.034) and a higher incidence of NIV support and HDU admission (30.77% vs 9.68%) (p=0.042). The main findings of our study suggest that older patients with lower serum concentrations of 25(OH)D, when compared with aged-matched vitamin D-replete patients, may demonstrate worse outcomes from COVID-19. In non-communicable diseases, both viral and bacterial, vitamin D deficiency has been associated with increased morbidity and mortality as well as a higher incidence of acute respiratory distress syndrome in critically unwell patients. • Older patients with COVID-19 infection and vitamin D deficiency (≤30 nmol/L) have higher peak D-dimer level and higher incidence of NIV support and HDU admission.
cord-296836-aizquh16	2020	We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30–50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50–75 years from Saarland, Germany. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D(3) supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women. We previously assessed the prevalence of vitamin D insufficiency and deficiency and their association with all-cause mortality and mortality from cardiovascular, cancer and respiratory diseases during a mean follow-up of 9.5 years in a cohort of 9548 adults aged 50-75 years from Saarland, Germany [4] [5] [6] [7] [8] .
cord-298542-4du3gar7	2020	title: The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate The main goal of this study was to evaluate if there was any association between the DBP gene polymorphism at rs7041 and rs4588 loci and the prevalence of COVID‐19 and its mortality rates caused among populations of 10 countries including Turkey. The main goal of this study was to evaluate if there is any association between the DBP gene polymorphism at rs7041 and rs4588 loci and the prevalence of COVID-19 and its mortality rates caused among populations of ten countries including Turkey. 26 Regarding the genetic susceptibility to a viral infection in vitamin D deficiency, we also observed significant correlations between rs7041 polymorphism and prevalence of COVID-19 and mortality rates per country. Allelic variants of the DBP gene have been studied extensively for their association with vitamin D deficiency 29, 30 and viral infections.
cord-300192-fgueg4mo	2020	Recent scientific evidence has indicated that the elderly have increased risk of COVID-19 infections, with over 70s and 80s being hardest hit – especially residents of care homes and in clinical settings, ethnic minorities, people who work indoors and those who are overweight and obese. Many of the risk factors identified so far that are related to viral infections and deaths from COVID-19 have underlying associations with nutritional status and specific essential nutrients that are known to contribute to the normal functions of the immune system. Furthermore, consumption of excessive quantities of some micronutrients can have adverse metabolic and health effects, and total intakes of each nutrient from all food and food supplement sources must take into account the tolerable upper safe level set by expert scientific committees such as European Food Safety Authority (78) , the Food and Nutrition Board/Institute of Medicine in the USA (31, 47, 79) and the UK Expert Vitamin and Mineral Group (80) .
cord-303917-2tu707ng	2020	We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children''s RNA‐virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, Semba et al 12 had reported that vitamin A supplementation reduced morbidity and mortality in different infectious diseases, such as measles, diarrheal disease, measles-related pneumonia, human immunodeficiency virus (HIV) infection, and malaria. 15 The mechanism by which vitamin A and retinoids inhibit measles replication is upregulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection during subsequent rounds of viral replication. Remdesivir (RDV), a nucleoside analog GS-5734, had been reported to inhibit human and zoonotic coronavirus in vitro and to restrain severe acute respiratory syndrome coronavirus (SARS-CoV) in vivo. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association
cord-310738-fnsf2qqm	2020	The aim of this study was to measure serum 25(OH)D, vitamin B12, and zinc levels in COVID-19 positive pregnant women to evaluate the role of these micronutrients in treatment and prevention. The aim of this study was to measure serum 25(OH)D, vitamin B12, and zinc levels in COVID-19 positive pregnant women to evaluate the role of these micronutrients in the prevention and to evaluate the possible cause between the blood levels of micronutrients and the COVID-19 infection. Pregnant women whose PCR test was positive for COVID-19, pregnancies older than eight weeks of gestation, and women who did not receive any antibacterial or antiviral treatment during the past three months or did not receive any 25(OH)D, vitamin B12, and zinc supplements during their pregnancy were included in the study. Additionally, it has been shown that serum zinc levels correlate positively with better immune response in pregnant women against infections [17] .
cord-311965-3x3tjzhi	2020	Adequate supply of zinc, selenium, and vitamin D is essential for resistance to other viral infections, immune function, and reduced inflammation. Clinical and subclinical micronutrient deficiencies common in older adults are known to contribute to decreased immune function and age-related diseases [11] , implying that nutritional management is essential to reduce the risk of severe infection [12] . In view of a lack of clinical data on preventive and/or therapeutic efficiency of the nutritive adequacy of selenium, zinc, and vitamin D in COVID-19, we, in the present narrative review, discussed recent clinical data on the role of these micronutrients in the protection against bronchopulmonary infections, as well as the existing indications of their impact on COVID-19. We did a literature search for the period 2010-2020 on PubMed, Medline, and Google Scholar with the keywords of SARS, SARS-CoV-2, COVID 19, coronavirus, micronutrients (zinc, selenium, vitamin D), immune system, inflammation, prevention, and treatment.
cord-317265-n6x0r58i	2020	The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS: Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. SUMMARY: Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. The clinical link between active inflammatory pathways in ARDS and the vitamin deficiency clearly indicates why COVID-19 causes high mortality in patients with chronic lung diseases.
cord-317758-oym8s4af	2020	5 Ecologic studies show lower COVID-19 mortality in countries or regions with greater solar ultraviolet-B radiation (associated with increased cutaneous synthesis of vitamin D) or populations with higher mean 25(OH)D levels. 6 For example, among 212 COVID-19 patients at three South Asian hospitals, the risk of severe as opposed to mild illness was approximately eight times higher in those who were vitamin D deficient than in those who were vitamin D sufficient. In this period of heightened "vitamin D awareness," clinicians and public health authorities in countries that lack food fortification policies should advocate for a timely implementation of such policies to reduce vitamin D deficiency. Although additional research on its contribution to attenuating COVID-19 risk and severity is in progress, eliminating vitamin D deficiency will improve public health during the current pandemic and after the threat subsides.
cord-320959-sgdqhtns	2020	In membrane biophysics, Vitamin E is a linactant and a potent modulator of lateral phase separation that effectively reduces the line tension at the two-dimensional phase boundaries and thereby exponentially increases the surface viscosity of the pulmonary surfactant. Supplementation of pulmonary surfactants which retain moderate level of cholesterol and 10 controlled hypothermia for patients are recommended when the hypothesis that the line-active property of the vitamin derivative drives the pathogenesis of EVALI holds. Currently, there are 5 five established non-antioxidative properties of Vitamin E in the biological system: i) its ability to induce gel-liquid crystalline phase transition, ii) its active deposition in the lipid droplet of macrophages, iii) its modulation of the antidiabetic cascade involving diacylglycerol kinase (DGK) and protein kinase C (PKC), iv) its activation of the xenobiotic-sensing pregnane X receptor (PXR) signaling, and v) its ability to modulate lateral phase separation.
cord-321401-w4ne60fn	2020	
cord-321817-z9oj9nmv	2020	• The involvement of vitamin in the pathophysiology of COVID-19 is still not clear; • Some studies support a link between vitamin D deficiency and worse COVID-19 outcome; • Vitamin D may also enhance macrophages activation and aberrant immune response; • In our study vitamin D supplementation was associated with a trend to higher mortality; • Supplementation trials are crucial to clarify the role of vitamin D in COVID-19. The observation of lower mortality rates at lower degrees of latitude, along with other preliminary reports on the association between serum levels of 25OHD and the risk of having the disease or a critical outcome, have suggested that vitamin D could modulate the risk and mitigate the severity of COVID-19 [1, 2, 5] . Therefore, we aimed to evaluate whether vitamin 25OHD supplementation, which may be a better surrogate of real 25OHD status, is associated with prognosis in COVID-19 patients from the Italian outbreak area of Lombardy. Further studies are needed to clarify the role of vitamin D supplementation and status in modulating the severity of COVID-19, as well as its prevention.
cord-322866-au76nnzg	2020	High‐dose VitD supplementation, particularly for risk groups, could be recommended to achieve and maintain optimal (range 40‐60 ng/mL) serum 25‐hydroxy vitamin D levels (marker of VitD status) both for COVID‐19 prevention and treatment. 17, 19, 26 Epidemiological studies of the past showed inverse relationships between VitD status and certain clinical events: lower 25OH-D levels are associated with higher risk of developing ARDS, heart failure and sepsis; the latter conditions are also known to increase risk for severe COVID-19 and death from COVID-19. Some authors even suggested that patients having VitD deficiency should be considered as high risk group for getting severe illness from COVID-19. 44, 45 VitD also increases the gene expression of antioxidative enzymes, eg glutathione reductase and glutamate-cysteine ligase modifier subunit, and this was shown to help maintain higher levels of vitamin C, which is an antioxidant and has antimicrobial activity as well, and is suggested as a potential agent for fighting COVID-19.
cord-322899-uxvlagt3	2020	Micronutrients play a critical role in the coordinated recruitment of innate and adaptive immune responses to viral infections, particularly in the regulation of pro-and anti-inflammatory host responses. [16] Zinc deficiency is associated with impaired immune responses and leads to a higher risk of respiratory viral infections, particularly in elderly subjects. [61] The beneficial effects of vitamin A on morbidity and mortality of some viral infections, such as measles and HIV, could be due to increased antibody production and lymphocyte proliferation as well as enhanced T-cell lymphopoiesis. [102] A modest level of vitamin E supplementation regulates the cellular free radical-antioxidant balance, enhances the antibody response, and activates the immune cells of broilers vaccinated with the infectious bronchitis virus. Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians
cord-324246-liyk6mna	2020	Vitamin B assists in proper activation of both the innate and adaptive immune responses, reduces pro-inflammatory cytokine levels, improves respiratory function, maintains endothelial integrity, prevents hypercoagulability and can reduce the length of stay in hospital [7, 8] . In a recent preprint it is suggested that PLP supplementation mitigates COVID-19 symptoms by regulating immune responses, decreasing pro-inflammatory cytokines, maintaining endothelial integrity and preventing hypercoagulability [22] . J o u r n a l P r e -p r o o f Vitamin B not only helps to build and maintain a healthy immune system but it could potentially prevent or reduce COVID-19 symptoms or treat SARS-CoV-2 infection. In particular, vitamin B modulates immune response by downregulating pro-inflammatory cytokines and inflammation, reducing breathing difficulty and gastrointestinal problems, preventing hypercoagulability, potentially improving outcomes and reducing the length of stay in the hospital for COVID-19 patients.
cord-324288-qgxswltx	2020	
cord-325436-pp3q022y	2020	This review presents key evidence on how functional foods and lifestyle approaches, including physical activity, effective for cardiometabolic disease prevention outcomes [9] , can also optimize the immune system response to viral infection, especially respiratory tract infections and COVID-19. Enhancing the antiviral immune defence can benefit from the functional food intake of a considerable variety of plant, animal, and fungi species, consumed across different diets and cultural practices including traditional herbal medicine such as teas, roots, mushrooms, and fermented plants and leaves; MD components such as olive-based products, oily fish, seeds, fruits, and vegetables; popular beverages such as coffee; and protein-rich foods such as chicken extract and soybean peptides. Below is a review of popular foods within various dietary patterns, including olive oil nutraceuticals, popular vitamins such as vitamin D, traditional medicinal herbs and roots, and protein peptides for preventing viral infections including COVID-19, especially when they are adopted as part of an active lifestyle.
cord-329321-usqjkj89	2020	We examine the biological plausibility and evidence for a role of vitamin D in COVID-19 patients, and provide a framework for guidance on supplementation, based on a rigorous and systematic approach. The first investigating the effectiveness of vitamin D in the prevention or treatment of infectious diseases reported that the strongest evidence was in reducing the risk of acute respiratory illness and influenza [38] . More recently, an individual patient meta-analysis of 25 trials, of over 11,000 participants, showed vitamin D supplementation to reduce the risk of acute respiratory infections, including viral, by 12% in all participants. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: A randomized controlled trial. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
cord-329997-jhejhz6d	2020	CoVID-19 has now been declared a pandemic by the World Health Organization, and people in all countries are under quarantine in order to reduce the spread of the virus, which then also lessens the impact on medical resources. Further, beyond sleep-inducing properties, milk products such as yogurt could also augmented natural killer cell activity and reduce the risk of respiratory infections [6] During quarantine the increased intake of macronutrients could also be accompanied by micronutrients deficiency as occurs in obesity [7] , which is commonly associated with impaired immune responses, particularly cell-mediated immunity, phagocyte function, cytokine production, secretory antibody response, antibody affinity, and the complement system, thus making more susceptible to viral infections [8] . In addition, quarantine could be associated to a less time spent outdoor, less sun-exposure, and reduced production of vitamin D as a result of lower levels of 7-dehydrocholesterol in the skin.
cord-330834-zqm4egei	2020	Since little is known about the impact of this supplementation on infant gut microbiota, we undertook a study to determine the association between maternal and infant vitamin D supplementation, infant gut microbiota composition and Clostridioides difficile colonization in 1,157 mother-infant pairs of the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study over 2009–2012. 2, 20 The primary objective of this study was to determine the association between maternal perinatal and infant vitamin D supplementation, and infant gut microbiota composition at 3 months of age, including C. These null associations were unchanged following adjustment for birth mode, maternal milk consumption, household pets, study center and infant age at sample collection ( Figure 1a , Table S1 ). 46 Ultimately, this study found evidence of an association between maternal vitamin D supplementation with the gut microbiota composition of all study infants, notably a lower abundance of Megamonas, with its potential implications for host defense against viral respiratory infections.
cord-331191-mq1zwpt7	2020	The quality-labeling category of high-quality (HQ) milk defined by the Italian legislation must comply with specific requirements concerning rigorous breeder management, hygienic controls, fat and protein content, bacterial load, somatic cells, lactic acid content, and non-denatured soluble serum proteins. Since the concentration of cholecalciferol in milk is important to assess the daily intake in humans, the present study aimed at evaluating the content of vitamin D3 in raw milk and pasteurized HQ whole milk obtained according to the Italian Ministerial Decree 185/1991 [11] . All FARM and PHQ samples were subjected to fat cold extraction according to the procedure described in Section 2.4, as well as to the determination and quantification of the vitamin D3 content by high performance liquid chromatography coupled to a photodiode array (HPLC/UV-DAD) detector and HPLC coupled to mass spectrometry (HPLC/MS).
cord-332533-iqe6sdq2	2020	
cord-333248-5342lyeu	2017	We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T celland innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. We studied how serum vitamins and antimicrobial peptide LL-37 levels and allergic and tonsillar diseases were associated with direct in vivo detection of respiratory viruses and T cell subset-related transcription factors, cytokines as well as type I, II and III interferons in tonsils. The associations of serum levels of vitamins and LL-37, allergy status and virus detection with intratonsillar cytokine and transcription factor expressions were analyzed using univariable and age-adjusted linear regression. This study provides new insights into connections between serum levels of vitamins A, D, and E and antimicrobial peptide LL-37 and several important outcomes: allergy, respiratory virus detection and tonsillar immune responses.
cord-335024-0klf75qr	2020	
cord-337849-tyabf12r	2015	
cord-338140-p88fgojk	2020	The purpose of this review is to provide concise guidance for the nutritional management of individuals with COVID-19 based on the current literature and focused on those in the non-ICU setting or with an older age and polymorbidity, which are independently associated with malnutrition and its negative impact on mortality. Numerous cases of pneumonia caused by a new virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were initially reported in Wuhan, China, at the end of December 2019. The purpose of this review is to summarize what is known about SARS-CoV-2 infection and provide possible and potential nutritional interventions on novel coronaviruses for clinicians. Older adults and polymorbid individuals suffering from chronic and acute disease conditions are at increased risk for poor outcomes and higher mortality following infection with the COVID-19-causing virus.
cord-339166-f7tw90tm	2020	Since hypovitaminosis D is very frequent in patients with diabetes and vitamin D (VD) has vascular protective properties, several studies have addressed the association of VD deficiency with DR and its severity and progression, whereas the effects of VD supplementation on its natural history are largely unknown. Moreover, several studies have addressed, without reaching to date an univocal conclusion, the prevalence and role of hypovitaminosis D in diabetes, as well as the impact of VD supplementation on the natural history of diabetes, blood Fig. 1 Metabolic pathways involved in the synthesis of VD, main external sources of VD and the potential mechanisms underlying widespread hypovitaminosis D (defined according to Sempos et al., 2018 [2] glucose control, and prevalence and severity of its macro and microvascular complications [6, 12] . Noteworthy, a sub-analysis of the Field Study, a placebo-controlled trial on nearly 10,000 T2DM patients, showed that subjects with hypovitaminosis D had a higher cumulative incidence of microvascular events; in fact, a 50 nmol/L difference in VD levels was associated with a 18% (p = 0.007) increase in risk of microvascular complications [83] .
cord-342335-awu50iev	2020	
cord-343122-lppdauei	2020	The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. (Isaia and Medico, 2020, p.1) a Reference studies show the role of optimal vitamin D levels in the prevention and control of severe respiratory infections. 12 hypothesize that supplementation with vitamin D, to increase concentrations in the general population, above 38 ng/ml, would result in significant health benefit, by reducing the burden of viral infections of the respiratory tract in healthy adults living in temperate climates. Adequate vitamin D status may play a role in prevention and management of respiratory tract infections, which might include the Covid-19 pandemic, especially among the older population and health professionals worldwide.
cord-345120-fa5sx5zm	2020	It would be wonderful if one or more of these agents is able to block the virus to prevent infection or treat sick patients but one course of therapy from some of these biologicals may have a price tag of many thousands of dollars. A recent scientific article published in 2019 before the detection of the novel coronavirus presents a metaanalysis of 18 controlled clinical trials with a total of more than 2000 patients looking at the effect of vitamin C on length of stay in the hospital intensive care unit and the duration of mechanical ventilation. Study results included the following: In 12 of the trials reviewed, length of ICU stay was reduced by 7.8% in patients receiving vitamin C. 8 Study design calls for intravenous administration of either 12 Gm. of vitamin C or placebo to patients with severe pneumonia due to COVID-19 infection twice a day for 7 days.
cord-348567-rvwxysvc	2020	
cord-352744-dd2rbsla	2020	In particular, it plays a key role in the control of the cytokine storm, i.e., the sudden acute increase in circulating levels of different pro-inflammatory cytokines, induced in several inflammatory conditions and also in COVID-19 (7) . ACE2 plays a protective role in acute respiratory distress syndrome and higher levels of ACE2 seem to be associated with better outcomes for lung diseases and, in particular, for COVID-19 (11) (12) (13) . To note, epidemiological data indicate that COVID-19 has a significantly higher lethality in men than in women (ratios up to 3:1), suggesting the presence of sex-dependent biological factors underlying these differences in disease outcome (16, 17) . Interestingly, sex differences have been observed in the immunomodulatory and anti-inflammatory effects of Vitamin D3 in some autoimmune diseases. In particular, it is tempting to hypothesize that the synergy between Vitamin D3 and estrogen could affect the sex differences in the outcome of patients with COVID-19.