Chiscano-Camón, L.

Ferrer, Ricard

Roca, O.

Ruiz-Rodriguez, J.C.

Ruiz-Sanmartin, A.

English

Chiscano-Camón, Luis

Ruiz-Rodriguez, J. C.

Diposit Digital de Documents de la UAB

RESEARCH LETTER Open AccessVitamin C levels in patients with SARS-CoV-2-associated acute respiratory distresssyndromeLuis Chiscano-Camón1,2,3, Juan Carlos Ruiz-Rodriguez1,2,3*, Adolf Ruiz-Sanmartin1,2, Oriol Roca1,2,3,4 andRicard Ferrer1,2,3,4Vitamin C is an antioxidant with anti-inflammatory andimmune-supportive properties. Its levels are decreasedin patients with sepsis-related acute respiratory distresssyndrome (ARDS). Moreover, a significant number ofpatients with severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) disease developed ARDS[1]. Therefore, we hypothesized that ARDS coronavirusdisease 2019 (COVID-19) patients may present vitaminC deficiency.Plasma vitamin C levels in a population of adultICU patients COVID-19 who met ARDS criteria ac-cording to the Berlin definition [2] were prospectivelymeasured. The study was approved by the localClinical Research Ethics Committee (PR (AG)270/2020). Main characteristics of the population includedare presented in Table 1. None of the patients in-cluded presented shock or sepsis on admission.Equally, no bacterial co-infection during their ICUcourse was documented. All patients survived. Vita-min C was determined by high-performance liquidchromatography with photodiode detector (detectionlimit 1.5 mg/L). Vitamin C reference values in generalpopulation used to be above 5 mg/L. Seventeen pa-tients (94.4%) had undetectable vitamin C levels and1 patient had low levels (2.4 mg/L).To our knowledge, this is the first study to analyze thelevels of vitamin C in patients with SARS-CoV-2-associ-ated ARDS. Our study revealed that vitamin C levels areundetectable in more than 90% of the patients included.The mechanisms of this significant reduction in vitaminC are uncertain. We hypothesized that several mecha-nisms, such as increased metabolic consumption due tothe enhanced inflammatory response, glomerular hyper-filtration, dialysis, decreased gastrointestinal absorption,or decreased recycling of dehydroascorbate to ascorbicacid, may be involved.Moreover, vitamin C may have implications for treat-ment of COVID-19-associated ARDS [3]. Indeed, onepreclinical study showed that vitamin C increased resist-ance to infection caused by coronavirus [4]. Moreover,other clinical studies that included surgical patients andpatients with pneumonia showed encouraging results interms of decreased incidence and severity of lung injuryand mortality [5].© 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 giveappropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission 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 thedata made available in this article, unless otherwise stated in a credit line to the data.* Correspondence: jcruiz@vhebron.net1Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’HebronBarcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035,Spain2Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’HebronHospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Valld’Hebron 119-129, Barcelona 08035, SpainFull list of author information is available at the end of the articleChiscano-Camón et al. Critical Care          (2020) 24:522 https://doi.org/10.1186/s13054-020-03249-yOur study has several limitations mainly related withthe fact that it is a unicentric study with small samplesize and blood sample was obtained in different days oftheir course in the ICU.In conclusion, in our cohort of patients withCOVID-19-associated ARDS, the levels of vitamin Care extremely low. Despite the limited generalizationof these results, we think these findings might stimu-late clinicians to measure vitamin C levels in COVID-19 patients to describe the real impact of thisalteration.AcknowledgementsNo contributions from individuals or organizations.Disclosure statementThe authors have no conflicts of interest to declare.Authors’ contributionsWe were all involved in providing care for the patient. We were all involvedin writing and reviewing the manuscript. The authors read and approved thefinal manuscript.FundingNo funding.Availability of data and materialsThe datasets used and/or analyzed during the current study are availablefrom the corresponding author on reasonable request.Ethics approval and consent to participateWe complied with the guidelines for human studies and our research wasconducted ethically in accordance with the World Medical AssociationDeclaration of Helsinki. Information revealing the subject’s identity is to beavoided. The study was approved by the local Clinical Research EthicsCommittee (PR (AG)270/2020) with exemption from informed consent.Competing interestsThe authors declare that they have no competing interests.Table 1 Clinical characteristics of the COVID-19 patients included. We have included the worst PF and highest PEEP. Results ofcontinuous variables are expressed as mean and standard deviation or median and interquartile range as appropriate. Categoricalvariables are expressed as frequency (percentage). SOFA sequential organ failure assessment, APACHE II Acute Physiology andChronic Health disease Classification System II, ICU intensive care unit, PF PaO2/FiO2 ratio, PEEP positive end-expiratory pressure, AKIacute kidney injury, CRRT continuous renal replacement therapy, LMWH low-molecular-weight heparinClinical characteristics COVID-19 ARDS (n = 18)Age (mean, standard deviation, years) 59 ± 9Male (n, %) 7 (38)SOFA score (median, interquartile range, points) 4 (1)APACHE II score (mean, standard deviation, points) 16.2 ± 1.6Interval between ICU admission and blood samples extraction for vitamin C measurement (mean, standard deviation, days) 17.5 ± 1.7Interval between intubation and blood samples extraction for vitamin C measurement (mean, standard deviation, days) 17.5 ± 1.7ARDS-related variablesPaO2/FIO2 at the time of vitamin C measurement (mean, standard deviation, mmHg) 94.4 ± 5.9PEEP (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 failureAKI (n, %) 3/18 (16)AKI I (n, %) 2/3 (66)AKI III (n, %) 1/3 (33)CRRT (n, %) 1/18 (6)COVID-19-related therapiesAntivirals (n, %) 14 (77)Hydroxychloroquine (n, %) 17 (94)Tocilizumab (n, %) 13 (72)Methylprednisolone (n, %) 10 (55)LMWH anticoagulant (n, %) 8 (44)OutcomesLength of ICU stay (mean, standard deviation, days) 28.4 ± 3.4Number of hospital survivors (n, %) 18 (100)Chiscano-Camón et al. Critical Care          (2020) 24:522 Page 2 of 3Author details1Intensive Care Department, Vall d’Hebron Hospital Universitari, Vall d’HebronBarcelona Hospital Campus, Passeig Vall d’Hebron 119-129, Barcelona 08035,Spain. 2Shock, Organ Dysfunction and Resuscitation Research Group, Valld’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus,Passeig Vall d’Hebron 119-129, Barcelona 08035, Spain. 3Departament deMedicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain. 4CiberEnfermedades Respiratorias (Ciberes), Instituto de Salud Carlos III, Madrid,Spain.Received: 16 July 2020 Accepted: 12 August 2020References1. 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 respiratorydistress 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 withCOVID-19. Crit Care. 2020;24:133.4. Atherton JG, Kratzing CC, Fisher A. The effect of ascorbic acid on infectionof 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 IIIsurgical patients. Ann Surg. 2002;236:814–22.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Chiscano-Camón et al. Critical Care          (2020) 24:522 Page 3 of 3

Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome

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Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome

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