The Prophylactic Effect of Vitamin C and Vitamin B12 against Ultraviolet-C-Induced Hepatotoxicity in Male Rats.

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm2) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant-antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1ß, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction.

Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 µg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.

Association of Oral or Intravenous Vitamin C Supplementation with Mortality: A Systematic Review and Meta-Analysis.

Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.

The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact on health systems, food supplies, and population health. This is the first study to examine the association between zinc and vitamin C intakes and the risk of disease severity and symptoms among COVID-19 patients. METHODS: This cross-sectional study included 250 recovered COVID-19 patients aged 18-65 years from June to September 2021. Data on demographics, anthropometrics, medical history, and disease severity and symptoms were collected. Dietary intake was evaluated using a web-based, 168-item food frequency questionnaire (FFQ). The severity of the disease was determined using the most recent version of the NIH COVID-19 Treatment Guidelines. Using multivariable binary logistic regression, the association between zinc and vitamin C intakes and the risk of disease severity and symptoms in COVID-19 patients was evaluated. RESULTS: The mean age of participants in this study was 44.1 ± 12.1, 52.4% of them were female, and 46% had a severe form of the disease. Participants with higher zinc intakes had lower levels of inflammatory cytokines, such as C-reactive protein (CRP) (13.6 vs. 25.8 mg/l) and erythrocyte sedimentation rate (ESR) (15.9 vs. 29.3). In a fully adjusted model, a higher zinc intake was also associated with a lower risk of severe disease (OR: 0.43; 95% CI: 0.21, 0.90, P-trend = 0.03). Similarly, participants with higher vitamin C intakes had lower CRP (10.3 vs. 31.5 mg/l) and ESR serum concentrations (15.6 Vs. 35.6) and lower odds of severe disease after controlling for potential covariates (OR: 0.31; 95% CI: 0.14, 0.65, P-trend = <0.01). Furthermore, an inverse association was found between dietary zinc intake and COVID-19 symptoms, such as dyspnea, cough, weakness, nausea and vomiting, and sore throat. Higher vitamin C intake was associated with a lower risk of dyspnea, cough, fever, chills, weakness, myalgia, nausea and vomiting, and sore throat. CONCLUSION: In the current study, higher zinc and vitamin C intakes were associated with decreased odds of developing severe COVID-19 and its common symptoms.

Vitamin C promotes ACE2 degradation and protects against SARS-CoV-2 infection.

ACE2 is a major receptor for cellular entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2 binding, strategies to flexibly and sufficiently reduce ACE2 levels for the prevention of SARS-CoV-2 infection have not been explored. Here, we reveal vitamin C (VitC) administration as a potent strategy to prevent SARS-CoV-2 infection. VitC reduces ACE2 protein levels in a dose-dependent manner, while even a partial reduction in ACE2 levels can greatly inhibit SARS-CoV-2 infection. Further studies reveal that USP50 is a crucial regulator of ACE2 levels. VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression. Importantly, VitC administration reduces host ACE2 levels and greatly blocks SARS-CoV-2 infection in mice. This study reveals that ACE2 protein levels are down-regulated by an essential nutrient, VitC, thereby enhancing protection against infection of SARS-CoV-2 and its variants.

Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2: A narrative review.

BACKGROUND: COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. METHODS: We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. RESULTS: Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. CONCLUSION: There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.

Introduction: Ascorbic acid and calcitriol were frequently utilized in conjunction as therapy during the COVID-19 pandemic, and individuals with minor symptoms had notable improvements. There have been a few studies, often with conflicting findings, that examine the use of them for endothelium restoration and numerous clinical trial studies that failed to establish the efficacy. The aim of this study was to find the efficacy of ascorbic acid compared to calcitriol on the inflammatory markers monocyte chemoattractant protein-1 (MCP-1), nitric oxide (NO), and superoxide dismutase (SOD), as protective agents which play an important role in the early stages of atherosclerosis formation. This study was an experimental in vivo study. Methods: The total of 24 male Rattus norvegicus strain Wistar rats were divided into 4 groups, namely: control/normal group (N), atherosclerosis group (DL) given atherogenic diet, atherosclerosis group given atherogenic diet and ascorbic acid (DLC), and atherosclerosis group given atherogenic diet and calcitriol (DLD) treatment for 30 days. Results: Ascorbic acid and calcitriol treatment was significantly effective (P<0.05) in lowering expression of MCP-1 and increasing NO and SOD level. Calcitriol was superior to ascorbic acid in increasing SOD (P<0.05). There was no significant difference between ascorbic acid and calcitriol in decreasing MCP-1 and increasing NO (P>0.05). Discussion: Both treatments could reduce MCP-1, and increase NO and SOD by increasing antioxidants. In this study calcitriol was superior to ascorbic acid in increasing SOD, but not NO and decreasing MCP-1. According to the theory, it was found that calcitriol through nuclear factor erythroid 2-related factor 2 (Nrf2) causes a direct increase in the amount of SOD. Nrf2 is an emerging regulator of cellular resistance to oxidants. Conclusion: Ascorbic acid and calcitriol treatment was able to reduce MCP-1 and increase NO and SOD in atherosclerosis rat. Calcitriol was significantly superior in increasing SOD levels compared to ascorbic acid.

Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.

Baseline serum vitamin A and vitamin C levels and their association with disease severity in COVID-19 patients.

AIM: We aimed to investigate the association between the serum concentrations of Vitamin A and Vitamin C and the severity of the COVID-19.  Methods: Fifty-three consecutive PCR (+) COVID-19 patients admitted to a dedicated ward were enrolled in this study. Blood samples for serum Vitamin A and C measurements were drawn from all participants upon admission. All subjects underwent thoracic CT imaging prior to hospitalization. CT severity score (CT-SS) was then calculated for determining the extent of pulmonary involvement. A group of healthy volunteers, in whom COVID-19 was ruled out, were assigned to the control group (n=26). These groups were compared by demographic features and serum vitamin A and C levels. The relationship between serum concentrations of these vitamins and pre-defined outcome measures, CT-SS and length of hospitalization (LOH), was also assessed.  Results: In COVID-19 patients, serum Vitamin A (ng/ml, 494±96 vs. 698±93; p<0.001) and Vitamin C (ng/ml, 2961 [1991-31718] vs. 3953 [1385-8779]; p=0.007) levels were significantly lower with respect to healthy controls. According to the results of correlation analyses, there was a significant negative association between Vitamin A level and outcome measures (LOH, r=-0.293; p=0.009 and CT-SS, r=-0.289; p=0.010). The negative correlations between Vitamin C level and those measures were even more prominent (LOH, r=-0.478; p<0.001 and CT-SS, r=-0.734: p<0.001). CONCLUSION: COVID-19 patients had lower baseline serum Vitamin A and Vitamin C levels as compared to healthy controls. In subjects with COVID-19, Vitamin A and Vitamin C levels were negatively correlated with CT-SS and LOH.

Hmong microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C): A phase II clinical study protocol.

BACKGROUND: Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success. OBJECTIVES: The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia. METHODS: This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition. EXPECTED RESULTS: We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).

Clinical, demographic and oxidative profile of patients with COVID-19 and disease severity.

This study aimed to profile the clinical progression, demographics, and oxidative status of COVID-19 patients, correlating with disease severity. The study included 143 participants: 93 patients with COVID-19 (28 outpatients, 65 inpatients), and 50 control participants. Thiobarbituric acid reactive substance (TBARS) was used as an oxidative damage marker. Antioxidant activity was assessed via quantification of Vitamin C, sulfhydryl groups, ferric reduction ability of plasma (FRAP), Uric acid (UA), and evaluation of delta-aminolevulinate dehydratase (δ-ALA-D) enzymatic activity. Geriatric patients, especially men, with comorbidities such as obesity and/or chronic diseases were more likely to develop the most severe form of COVID-19. The activity of the δ-ALA-D was lower in inpatients, and there was no significant difference with the outpatient. Antioxidants decreased in COVID-19 groups, while lipid peroxidation increased. FRAP and Vitamin C decreased with evolution of the disease. Oxidative stress could be used as a predictor of worsening clinical condition.

Inhibition of SARS-CoV-2 Mpro with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination.

BACKGROUND: Drug resistance is a critical problem in health care that affects therapy outcomes and requires new approaches to drug design. SARS-CoV-2 Mpro mutations are of concern as they can potentially reduce therapeutic efficacy. Viral infections are amongst the many disorders for which nutraceuticals have been employed as an adjunct therapy. The aim of this study was to examine the potential in vitro activity of L-arginine and vitamin C against SARS-CoV-2 Mpro. METHODS: The Mpro inhibition assay was developed by cloning, expression, purification, and characterization of Mpro. Selected compounds were then screened for protease inhibition. RESULTS: L-arginine was found to be active against SARS-CoV-2 Mpro, while a vitamin C/L-arginine combination had a synergistic antiviral action against Mpro. These findings confirm the results of our previous in silico repurposing study that showed L-arginine and vitamin C were potential Mpro inhibitors. Moreover, they suggest a possible molecular mechanism to explain the beneficial effect of arginine in COVID patients. CONCLUSIONS: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.

Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study.

Vitamin C, (ascorbic acid), vitamin D (cholecalciferol) and zinc (zinc sulfate monohydrate) supplements are important in immunity against coronavirus disease-2019 (COVID-19). However, a limited number of studies have been conducted on the association of vitamins and supplements with the reduced risks of COVID-19 infection. This study aims to evaluate the association of vitamins and supplements as treatment options to reduce the severity of COVID-19. Data were collected from 962 participants from 13 December 2020 to 4 February 2021. The presence of COVID-19 was confirmed by qRT-PCR. The Chi-square test and multivariate regression analyses were conducted. The ratio of uptake of vitamin C:vitamin D:zinc was 1:1:0.95. Uptake of vitamin C, vitamin D and zinc were significantly associated with the reduced risk of infection and severity of COVID-19 (OR: 0.006 (95% CI: 0.03-0.11) (p = 0.004)) and (OR: 0.03 (95% CI: 0.01-0.22) (p = 0.005)). The tendency of taking supplements was associated with the presence of infection of COVID-19 (p = 0.001), age (p = 0.02), sex (p = 0.05) and residence (p = 0.04). The duration of supplementation and medication was significantly associated with reduced hospitalization (p = 0.0001). Vitamins C, D and zinc were not significantly (p = 0.9) associated with a reduced risk of severity when taken through the diet. Hospitalization (p = 0.000001) and access to health facilities (p = 0.0097) were significantly associated with the survival period of the participants. Participants with better access to health facilities recovered early (OR: 6.21, 95% CI 1.56-24.7). This study will add knowledge in the field of treatment of COVID-19 by using vitamins and zinc supplements.

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial.

Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19 outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength, flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either l-arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51 (14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and completed the study. At 28 days, l-arginine plus vitamin C increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Intravenous high dose vitamin C and selected antiviral drugs in hospitalized COVID-19 patients: a descriptive cohort study.

INTRODUCTION: There is lack of universal agreement on the management of COVID-19. Intravenous high dose vitamin C (HDVC), remdesivir (RDV), and favipiravir (FPV) have been suggested as part of the treatment regimens and only RDV is approved by the Food and Drug Administration (FDA) so far. There is no study in Lebanon that addresses the descriptive cohort of HDVC and antiviral therapy amongst COVID-19 inpatients. Our goal was to highlight such a cohort. METHODOLOGY: A retrospective electronic chart review of COVID-19 inpatients was done over a period of 10 months (August 2020 to April 2021). Comparative data analysis was performed between HDVC and non-HDVC (NHDVC) groups, and RDV and FPV groups. RESULTS: Among HDVC patients, 70.1% (p = 0.035) and 67.2% (p = 0.008) had dyspnea and desaturation respectively. Patients on HDVC were less likely to remain in hospital for more than 20 days (p = 0.003). HDVC patients were more likely to be on oxygen therapy with 74.7% (p = 0.002). RDV patients were more likely to be on other COVID-19-related medications during hospitalization including the use of tofacitinib, baricitinib, tocilizumab, and anticoagulation as recommended in the guidelines. Statistical significance was noted for the status on discharge as 90.1% of the patients that received RDV were discharged after clinical improvement, compared to the 74.2% of the FPV patients. CONCLUSIONS: Further research is needed to establish local guidelines for the treatment of COVID-19. A significant role of HDVC and FPV might resurface if randomized control trials are conducted.