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      Serum levels of vitamin C and vitamin D in a cohort of critically ill COVID-19 patients of a north American community hospital intensive care unit in may 2020. A pilot study

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          Abstract

          Background

          The COVID-19 pandemic has placed an enormous and growing burden on the population and health infrastructure, warranting innovative ways to mitigate risk of contracting and developing severe forms of this disease. A growing body of literature raises the issue of Vitamin C and Vitamin D as a risk-assessment tool, and therapeutic option, in COVID-19.

          Objective

          The objective of this pilot study was to measure serum Vitamin C and Vitamin D levels in a cohort of patients with critical COVID-19 illness in our community hospital ICU, correlate with other illness risk factors (age, BMI, HgbA1c, smoking status), generate hypotheses, and suggest further therapeutic intervention studies.

          Method

          This pilot study included all 21 critically ill COVID-19 patients hospitalized in May 2020 in the ICU of North Suburban Medical Center, Thornton, Colorado, in whose care the principal investigator (C.A.) was involved. We measured patients' serum Vitamin C and Vitamin D levels, and standard risk factors like age, BMI, HbA1c, and smoking status. Variables in this study were gauged using descriptive statistics.

          Results

          Of 21 critically ill COVID-19 patients (15 males and 6 females, 17 Hispanic and 4 Caucasian, of median age 61 years, range 20–94), there were 11 survivors.

          Serum levels of Vitamin C and Vitamin D were low in most of our critically ill COVID-19 ICU patients.

          Older age and low Vitamin C level appeared co-dependent risk factors for mortality from COVID-19 in our sample.

          Insulin resistance and obesity were prevalent in our small cohort, but smoking was not.

          Conclusion

          Our pilot study found low serum levels of Vitamin C and Vitamin D in most of our critically ill COVID-19 ICU patients. Older age and low Vitamin C level appeared co-dependent risk factors for mortality. Many were also insulin-resistant or diabetic, overweight or obese, known as independent risk factors for low Vitamin C and Vitamin D levels, and for COVID-19.

          These findings suggest the need to further explore whether caring for COVID-19 patients ought to routinely include measuring and correcting serum Vitamin C and Vitamin D levels, and whether treating critically ill COVID-19 warrants acute parenteral Vitamin C and Vitamin D replacement.

          Highlights

          • The COVID-19 pandemic has posed an enormous burden, warranting innovative ways to mitigate risk of contracting and developing severe forms of this disease. A growing body of literature raises the issue of Vitamin C and Vitamin D as a risk-assessment tool, and therapeutic option, in COVID-19.

          • In our pilot study, we measured serum Vitamin C and Vitamin D levels in a cohort of patients with critical COVID-19 illness in our community hospital ICU, correlated with other standard risk factors like age, BMI, HbA1c, and smoking status; generated hypotheses, and suggest further therapeutic intervention studies.

          • Of the 21 critically ill COVID-19 patients we studied, 11 survived.

            Most of our critically ill COVID-19 ICU patients had low serum levels of Vitamin C and Vitamin D.

            Older age and low Vitamin C level appeared co-dependent risk factors for mortality.

            Many were also insulin-resistant or diabetic, overweight or obese, known as independent risk factors for low Vitamin C and Vitamin D levels, and for COVID-19.

          • Conclusion:

            Our pilot study found low serum levels of Vitamin C and Vitamin D in most of our critically ill COVID-19 ICU patients. Older age and low Vitamin C level appeared co-dependent risk factors for mortality.

            These findings suggest the need to further explore whether caring for COVID-19 patients ought to routinely include measuring and correcting serum Vitamin C and Vitamin D levels, and whether treating critically ill COVID-19 warrants acute parenteral Vitamin C and Vitamin D replacement.

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          Most cited references3

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          Is Open Access

          Vitamin C revisited

          This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.
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            Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome

            Vitamin C is an antioxidant with anti-inflammatory and immune-supportive properties. Its levels are decreased in patients with sepsis-related acute respiratory distress syndrome (ARDS). Moreover, a significant number of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease developed ARDS [1]. Therefore, we hypothesized that ARDS coronavirus disease 2019 (COVID-19) patients may present vitamin C deficiency. Plasma vitamin C levels in a population of adult ICU patients COVID-19 who met ARDS criteria according to the Berlin definition [2] were prospectively measured. The study was approved by the local Clinical Research Ethics Committee (PR (AG)270/2020). Main characteristics of the population included are presented in Table 1. None of the patients included presented shock or sepsis on admission. Equally, no bacterial co-infection during their ICU course was documented. All patients survived. Vitamin C was determined by high-performance liquid chromatography with photodiode detector (detection limit 1.5 mg/L). Vitamin C reference values in general population used to be above 5 mg/L. Seventeen patients (94.4%) had undetectable vitamin C levels and 1 patient had low levels (2.4 mg/L). Table 1 Clinical characteristics of the COVID-19 patients included. We have included the worst PF and highest PEEP. Results of continuous variables are expressed as mean and standard deviation or median and interquartile range as appropriate. Categorical variables are expressed as frequency (percentage). SOFA sequential organ failure assessment, APACHE II Acute Physiology and Chronic Health disease Classification System II, ICU intensive care unit, PF PaO2/FiO2 ratio, PEEP positive end-expiratory pressure, AKI acute kidney injury, CRRT continuous renal replacement therapy, LMWH low-molecular-weight heparin Clinical characteristics COVID-19 ARDS (n = 18) Age (mean, standard deviation, years) 59 ± 9 Male (n, %) 7 (38) SOFA score (median, interquartile range, points) 4 (1) APACHE II score (mean, standard deviation, points) 16.2 ± 1.6 Interval between ICU admission and blood samples extraction for vitamin C measurement (mean, standard deviation, days) 17.5 ± 1.7 Interval between intubation and blood samples extraction for vitamin C measurement (mean, standard deviation, days) 17.5 ± 1.7 ARDS-related variables  PaO2/FIO2 at the time of vitamin C measurement (mean, standard deviation, mmHg) 94.4 ± 5.9  PEEP (cmH2O) at the time of vitamin C measurement (median, interquartile range, points) 13.6 (3)  Neuromuscular blockade during ICU admission (n, %) 18 (100)  Prone position during ICU admission (n, %) 17 (94) Renal failure  AKI (n, %) 3/18 (16)   AKI I (n, %) 2/3 (66)   AKI III (n, %) 1/3 (33)  CRRT (n, %) 1/18 (6) COVID-19-related therapies  Antivirals (n, %) 14 (77)  Hydroxychloroquine (n, %) 17 (94)  Tocilizumab (n, %) 13 (72)  Methylprednisolone (n, %) 10 (55)  LMWH anticoagulant (n, %) 8 (44) Outcomes  Length of ICU stay (mean, standard deviation, days) 28.4 ± 3.4  Number of hospital survivors (n, %) 18 (100) To our knowledge, this is the first study to analyze the levels of vitamin C in patients with SARS-CoV-2-associated ARDS. Our study revealed that vitamin C levels are undetectable in more than 90% of the patients included. The mechanisms of this significant reduction in vitamin C are uncertain. We hypothesized that several mechanisms, such as increased metabolic consumption due to the enhanced inflammatory response, glomerular hyperfiltration, dialysis, decreased gastrointestinal absorption, or decreased recycling of dehydroascorbate to ascorbic acid, may be involved. Moreover, vitamin C may have implications for treatment of COVID-19-associated ARDS [3]. Indeed, one preclinical study showed that vitamin C increased resistance to infection caused by coronavirus [4]. Moreover, other clinical studies that included surgical patients and patients with pneumonia showed encouraging results in terms of decreased incidence and severity of lung injury and mortality [5]. Our study has several limitations mainly related with the fact that it is a unicentric study with small sample size and blood sample was obtained in different days of their course in the ICU. In conclusion, in our cohort of patients with COVID-19-associated ARDS, the levels of vitamin C are extremely low. Despite the limited generalization of these results, we think these findings might stimulate clinicians to measure vitamin C levels in COVID-19 patients to describe the real impact of this alteration.
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              Effect of a single 'megadose' intramuscular vitamin D (600,000 IU) injection on vitamin D concentrations and bone mineral density following biliopancreatic diversion surgery.

              Vitamin D (VitD) deficiency is common following biliopancreatic diversion (BPD). We conducted a prospective open-label study to evaluate the efficacy of a single intramuscular injection with 600,000 IU of cholecalciferol in an arachis oil depot formulation (VitD3, Arachitol Solvay Pharmacia) as an adjunct to regular oral VitD supplementation (Citrical+D) for a period of 12 months following BPD surgery. Some 29 patients who had undergone BPD during 2000-2005 were recruited and received a single injection of 600,000 IU of cholecalciferol. Venous blood VitD, parathyroid hormone (PTH), alkaline phosphatase (ALP), ionised calcium and urinary N-telopeptide (NTX) were assessed at baseline and at 1.5, 3, 6, 9 and 12 months post-injection. Bone mineral density (BMD) was determined at baseline and 12 months post-injection. VitD concentrations (mean +/- SD) were significantly increased from baseline values (61.5 +/- 18.8 nmol/L) at 1.5 months (92.4 +/- 21.5, p < 0.001), 3 months (100.5 +/- 24.4, p < 0.001) and 6 months (79.1 +/- 20.9, p = 0.014) post-injection, with non-significant elevations at 9 months (73.3 +/- 15.1, p = 0.248) and 12 months (73.4 +/- 17.3, p = 0.278). The proportion of patients with 'normalised' VitD levels was significantly higher at all post-injection time points (range, 93-100%) compared with baseline (71.4%; p < 0.01). Ionised calcium and ALP remained within normal levels at baseline and all follow-up time points, although ionised calcium decreased by 3.4% (p = 0.015) and ALP increased by 14.6% (p = 0.021) at 12 months compared with baseline. No significant change in PTH, NTX or BMD was observed. Intramuscular cholecalciferol injection, as an adjunct to oral supplementation, appears a safe and effective method to increase and maintain VitD levels after BPD.
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                Author and article information

                Journal
                Med Drug Discov
                Med Drug Discov
                Medicine in Drug Discovery
                The Author(s). Published by Elsevier B.V.
                2590-0986
                18 September 2020
                18 September 2020
                Affiliations
                [a ]Intensivist & Pulmonologist, North Suburban Medical Center, Thornton, CO 80229, USA
                [b ]Biostatistics, Advocate Aurora Research Institute, Advocate Aurora Health Care
                [c ]Research and Graduate Studies, Marquette University, School of Dentistry, Milwaukee, WI 53201, USA
                [d ]Pulmonary and Critical Care Medicine, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
                Author notes
                [* ]Corresponding author.
                Article
                S2590-0986(20)30051-8 100064
                10.1016/j.medidd.2020.100064
                7499070
                22179f2f-fa67-463e-a03f-828fc2dc95b5
                © 2020 The Author

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                Categories
                Article

                covid-19,sars-cov-2,critical illness,intensive care unit (icu),serum vitamin c,serum vitamin d,age,body mass index (bmi),hba1c (glycated hemoglobin)

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