Chiscano-Camón et al. Critical Care (2020) 24:522 https://doi.org/10.1186/s13054-020-03249-y RESEARCH LETTER Open Access Vitamin C levels in patients with SARS-CoV- 2-associated acute respiratory distress syndrome Luis Chiscano-Camón1,2,3, Juan Carlos Ruiz-Rodriguez1,2,3*, Adolf Ruiz-Sanmartin1,2, Oriol Roca1,2,3,4 and Ricard Ferrer1,2,3,4 Vitamin C is an antioxidant with anti-inflammatory and population used to be above 5 mg/L. Seventeen pa- immune-supportive properties. Its levels are decreased tients (94.4%) had undetectable vitamin C levels and in patients with sepsis-related acute respiratory distress 1 patient had low levels (2.4 mg/L). syndrome (ARDS). Moreover, a significant number of To our knowledge, this is the first study to analyze the patients with severe acute respiratory syndrome levels of vitamin C in patients with SARS-CoV-2-associ- coronavirus-2 (SARS-CoV-2) disease developed ARDS ated ARDS. Our study revealed that vitamin C levels are [1]. Therefore, we hypothesized that ARDS coronavirus undetectable in more than 90% of the patients included. disease 2019 (COVID-19) patients may present vitamin The mechanisms of this significant reduction in vitamin C deficiency. C are uncertain. We hypothesized that several mecha- Plasma vitamin C levels in a population of adult nisms, such as increased metabolic consumption due to ICU patients COVID-19 who met ARDS criteria ac- the enhanced inflammatory response, glomerular hyper- cording to the Berlin definition [2] were prospectively filtration, dialysis, decreased gastrointestinal absorption, measured. The study was approved by the local or decreased recycling of dehydroascorbate to ascorbic Clinical Research Ethics Committee (PR (AG)270/ acid, may be involved. 2020). Main characteristics of the population included Moreover, vitamin C may have implications for treat- are presented in Table 1. None of the patients in- ment of COVID-19-associated ARDS [3]. Indeed, one cluded presented shock or sepsis on admission. preclinical study showed that vitamin C increased resist- Equally, no bacterial co-infection during their ICU ance to infection caused by coronavirus [4]. Moreover, course was documented. All patients survived. Vita- other clinical studies that included surgical patients and min C was determined by high-performance liquid patients with pneumonia showed encouraging results in chromatography with photodiode detector (detection terms of decreased incidence and severity of lung injury limit 1.5 mg/L). Vitamin C reference values in general and mortality [5]. * Correspondence: jcruiz@vhebron.net 1 Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain 2 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Chiscano-Camón et al. Critical Care (2020) 24:522 Page 2 of 3 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) Our study has several limitations mainly related with Authors’ contributions the fact that it is a unicentric study with small sample We were all involved in providing care for the patient. We were all involved in writing and reviewing the manuscript. The authors read and approved the size and blood sample was obtained in different days of final manuscript. their course in the ICU. In conclusion, in our cohort of patients with Funding COVID-19-associated ARDS, the levels of vitamin C No funding. are extremely low. Despite the limited generalization of these results, we think these findings might stimu- Availability of data and materials late clinicians to measure vitamin C levels in COVID- The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. 19 patients to describe the real impact of this alteration. Ethics approval and consent to participate We complied with the guidelines for human studies and our research was conducted ethically in accordance with the World Medical Association Acknowledgements Declaration of Helsinki. Information revealing the subject’s identity is to be No contributions from individuals or organizations. avoided. The study was approved by the local Clinical Research Ethics Committee (PR (AG)270/2020) with exemption from informed consent. Disclosure statement The authors have no conflicts of interest to declare. Competing interests The authors declare that they have no competing interests. Chiscano-Camón et al. Critical Care (2020) 24:522 Page 3 of 3 Author details 1 Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain. 2Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain. 3Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain. 4Ciber Enfermedades Respiratorias (Ciberes), Instituto de Salud Carlos III, Madrid, Spain. Received: 16 July 2020 Accepted: 12 August 2020 References 1. Murthy S, Gomersall C, Fowler R. Care for critically ill patients with COVID- 19. JAMA. 2020. https://doi.org/10.1001/jama.2020.3633. 2. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutksy AS. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526–33. 3. Carr A. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020;24:133. 4. Atherton JG, Kratzing CC, Fisher A. The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus. Arch Viro. 1978;56:195–9. 5. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, et al. Randomized, prospective trial of antioxidant supplementation in critically III surgical patients. Ann Surg. 2002;236:814–22. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.