Vitamin C Deficiency in Blood Samples of COVID-19 Patients
Tobias Sinnberg, Christa Lichtensteiger, Katharina Hill-Mündel, Christian Leischner, Heike Niessner, Christian Busch, Olga Renner, Nina Wyss, Lukas Flatz, Ulrich M Lauer, Ludwig E Hoelzle, Donatus Nohr, Markus Burkard, Luigi Marongiu, Sascha Venturelli
Antioxidants, doi:10.3390/antiox11081580
Coronavirus disease 2019 (COVID-19) is the most notable pandemic of the modern era. A relationship between ascorbate (vitamin C) and COVID-19 severity is well known, whereas the role of other vitamins is less understood. The present study compared the blood levels of four vitamins in a cohort of COVID-19 patients with different severities and uninfected individuals. Serum concentrations of ascorbate, calcidiol, retinol, and α-tocopherol were measured in a cohort of 74 COVID-19 patients and 8 uninfected volunteers. The blood levels were statistically compared and additional co-morbidity factors were considered. COVID-19 patients had significantly lower plasma ascorbate levels than the controls (p-value < 0.001), and further stratification revealed that the controls had higher levels than fatal, critical, and severe COVID-19 cases (p-values < 0.001). However, no such trend was observed for calcidiol, retinol, or α-tocopherol (p-value ≥ 0.093). Survival analysis showed that plasma ascorbate below 11.4 µM was associated with a lengthy hospitalization and a high risk of death. The results indicated that COVID-19 cases had depleted blood ascorbate associated with poor medical conditions, confirming the role of this vitamin in the outcome of COVID-19 infection.
Conflicts of Interest: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
References
Ahammed, Anjum, Rahman, Haider, Kock et al., Estimation of novel coronavirus (COVID-19) reproduction number and case fatality rate: A systematic review and meta-analysis, Health Sci. Rep,
doi:10.1002/hsr2.274
Arvinte, Singh, Marik, 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, Med. Drug Discov
Bowie, O'neill, Vitamin C Inhibits NF-κB Activation by TNF via the Activation of p38 Mitogen-Activated Protein Kinase, J. Immunol,
doi:10.4049/jimmunol.165.12.7180
Braiman, Latitude Dependence of the COVID-19 Mortality Rate-A Possible Relationship to Vitamin D Deficiency?, SSRN,
doi:10.2139/ssrn.3561958
Brant, Tian, Majerciak, Yang, Zheng, SARS-CoV-2: From its discovery to genome structure, transcription, and replication, Cell Biosci,
doi:10.1186/s13578-021-00643-z
Caballero-García, Pérez-Valdecantos, Guallar, Caballero-Castillo, Roche et al., Effect of Vitamin D Supplementation on Muscle Status in Old Patients Recovering from COVID-19 Infection, Medicina
Carr, Rosengrave, Bayer, Chambers, Mehrtens et al., Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes, Crit. Care,
doi:10.1186/s13054-017-1891-y
Carr, Spencer, Dixon, Chambers, Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress, Nutrients,
doi:10.3390/nu12051318
Carstensen, Plummer, Laara, Hills, Epi, A Package for Statistical Analysis in Epidemiology
Cecchini, Cecchini, SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression, Med. Hypotheses,
doi:10.1016/j.mehy.2020.110102
Chen, Luo, Yuan, Wang, Yang et al., Vitamin C Mitigates Oxidative Stress and Tumor Necrosis Factor-Alpha in Severe Community-Acquired Pneumonia and LPS-Induced Macrophages, Mediat. Inflamm,
doi:10.1155/2014/426740
Chiscano-Camón, Ruiz-Rodriguez, Ruiz-Sanmartin, Roca, Ferrer, Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome, Crit. Care,
doi:10.1186/s13054-020-03249-y
Crook, Horgas, Yoon, Grundmann, Johnson-Mallard, Insufficient Vitamin C Levels among Adults in the United States: Results from the NHANES Surveys, 2003-2006, Nutrients,
doi:10.3390/nu13113910
Erol, Saglam, Saglam, Erol, Altun et al., The Protection Potential of Antioxidant Vitamins Against Acute Respiratory Distress Syndrome: A Rat Trial, Inflammation,
doi:10.1007/s10753-019-01020-2
Fisher, Kraskauskas, Martin, Farkas, Wegelin et al., None
Frese, Schmerer, Wortmann, Schürmann, König et al., Imaging of SARS-CoV-2 infected Vero E6 cells by helium ion microscopy, Beilstein J. Nanotechnol,
doi:10.3762/bjnano.12.13
Gombart, Pierre, Maggini, A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection, Nutrients,
doi:10.3390/nu12010236
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients,
doi:10.3390/nu12040988
Hati, Bhattacharyya, Impact of Thiol-Disulfide Balance on the Binding of COVID-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor, ACS Omega,
doi:10.1021/acsomega.0c02125
Hemilä, Carr, Chalker, Vitamin C May Increase the Recovery Rate of Outpatient Cases of SARS-CoV-2 Infection by 70%: Reanalysis of the COVID A to Z Randomized Clinical Trial, Front. Immunol,
doi:10.3389/fimmu.2021.674681
Hemilä, Chalker, Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis, Nutrients,
doi:10.3390/nu11040708
Hiedra, Lo, Elbashabsheh, Gul, Wright et al., The use of IV vitamin C for patients with COVID-19: A case series, Expert Rev. Anti-Infect. Ther,
doi:10.1080/14787210.2020.1794819
Holford, Carr, Jovic, Ali, Whitaker et al., Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19, Nutrients,
doi:10.3390/nu12123760
Holford, Carr, Zawari, Vizcaychipi, Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence, Life,
doi:10.3390/life11111166
Hu, Guo, Zhou, Shi, Characteristics of SARS-CoV-2 and COVID-19, Nat. Rev. Microbiol
Jacob, Skala, Omaye, Biochemical indices of human vitamin C status, Am. J. Clin. Nutr
Jamalimoghadamsiahkali, Zarezade, Koolaji, Seyedalinaghi, Zendehdel et al., Safety and effectiveness of high-dose vitamin C in patients with COVID-19: A randomized open-label clinical trial, Eur. J. Med. Res,
doi:10.1186/s40001-021-00490-1
Jovic, Ali, Ibrahim, Jessop, Tarassoli et al., Could Vitamins Help in the Fight against COVID-19?, Nutrients,
doi:10.3390/nu12092550
Kumari, Dembra, Dembra, Bhawna, Gul et al., The Role of Vitamin C as Adjuvant Therapy in COVID-19, Cureus,
doi:10.7759/cureus.11779
Lauer, Burkard, Niessner, Leischner, Renner et al., Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model, Nutrients,
doi:10.3390/nu13072366
Li, Fan, Lai, Han, Li et al., Coronavirus infections and immune responses, J. Med. Virol,
doi:10.1002/jmv.25685
Mccartney, Byrne, Optimisation of Vitamin D Status for Enhanced Immuno-protection against COVID-19, Ir. Med. J
Meyerowitz-Katz, Merone, A systematic review and meta-analysis of published research data on COVID-19 infection fatality rates, Int. J. Infect. Dis. IJID Off. Publ. Int. Soc. Infect. Dis,
doi:10.1016/j.ijid.2020.09.1464
Muhammad, Kani, Iliya, Muhammad, Binji et al., Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria, SAGE Open Med,
doi:10.1177/2050312121991246
Natarajan, Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid, Am. J. Physiol.-Lung Cell. Mol. Physiol,
doi:10.1152/ajplung.00300.2011
Pinnawala, Thrastardottir, Constantinou, Keeping a Balance during the Pandemic: A Narrative Review on the Important Role of Micronutrients in Preventing Infection and Reducing Complications of COVID-19, Curr. Nutr. Rep,
doi:10.1007/s13668-021-00356-2
Quek, Ooi, Teng, Chan, Ng et al., Zinc and vitamin C intake increases spike and neutralising antibody production following SARS-CoV-2 infection, Clin. Transl. Med,
doi:10.1002/ctm2.731
Ranieri, Rubenfeld, Thompson, Ferguson, Caldwell et al., Acute respiratory distress syndrome: The Berlin Definition, JAMA,
doi:10.1001/jama.2012.5669
Reider, Chung, Devarshi, Grant, Hazels Mitmesser, Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES, Nutrients,
doi:10.3390/nu12061735
Sarohan, Kızıl, ˙inkaya, Mahmud, Akram et al., A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder, Cell. Signal,
doi:10.1016/j.cellsig.2021.110121
Suhail, Zajac, Fossum, Lowater, Mccracken et al., Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review, Protein J,
doi:10.1007/s10930-020-09935-8
Tehrani, Yadegarynia, Abrishami, Moradi, Gharaei et al., An investigation into the Effects of Intravenous Vitamin C on Pulmonary CT Findings and Clinical Outcomes of Patients with COVID 19 Pneumonia A Randomized Clinical Trial, Urol. J,
doi:10.22037/uj.v18i.6863
Tepasse, Vollenberg, Fobker, Kabar, Schmidt et al., Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis, Nutrients,
doi:10.3390/nu13072173
Vankadari, Wilce, Emerging WuHan (COVID-19) coronavirus: Glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26, Emerg. Microbes Infect,
doi:10.1080/22221751.2020.1739565
Venturelli, Leischner, Helling, Burkard, Marongiu, Vitamins as Possible Cancer Biomarkers: Significance and Limitations, Nutrients,
doi:10.3390/nu13113914
Venturelli, Sinnberg, Berger, Noor, Levesque et al., Epigenetic Impacts of Ascorbate on Human Metastatic Melanoma Cells, Front. Oncol,
doi:10.3389/fonc.2014.00227
Venturelli, Sinnberg, Niessner, Busch, Molecular mechanisms of pharmacological doses of ascorbate on cancer cells, Wien. Med. Wochenschr,
doi:10.1007/s10354-015-0356-7
Vollbracht, Kraft, Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue, Nutrients,
doi:10.3390/nu13041154
Yamada, Shimojima, Narita, Tsukamoto, Kato et al., RIG-I-Like Receptor and Toll-Like Receptor Signaling Pathways Cause Aberrant Production of Inflammatory Cytokines/Chemokines in a Severe Fever with Thrombocytopenia Syndrome Virus Infection Mouse Model, J. Virol,
doi:10.1128/JVI.02246-17
Yang, Wang, Liu, Shang, Cheng et al., Traditional Chinese medicine together with high-dose vitamin C improves the therapeutic effect of western medicine against COVID-19, Am. J. Transl. Res
Zabet, Mohammadi, Ramezani, Khalili, Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock, J. Res. Pharm. Pract,
doi:10.4103/2279-042X.179569
Zhang, Rao, Li, Zhu, Liu et al., Pilot trial of high-dose vitamin C in critically ill COVID-19 patients, Ann. Intensive Care,
doi:10.1186/s13613-020-00792-3
Zhao, Ling, Li, Peng, Huang et al., Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: A retrospective case series study, Ann. Palliat. Med,
doi:10.21037/apm-20-1387
Zhao, Liu, Liu, Peng, Huang et al., High Dose Intravenous Vitamin C for Preventing the Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched before-after Study, Front. Pharmacol,
doi:10.3389/fphar.2021.638556
Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature,
doi:10.1038/s41586-020-2012-7