Association of Vitamin D with severity and outcome of COVID-19: Clinical and Experimental Evidence
Georgios Renieris, Spyros Foutadakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionysia-Eirini Droggiti, Dionysios Kafousopoulos, Theologia Gkavogianni, Georgia Damoraki, Giannis Vatsellas, MD Evangelos J Giamarellos-Bourboulis
Journal of Innate Immunity, doi:10.1159/000535302
Introduction: The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. Methods: 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 ARDS into C57/BL6 mice, mice were treated with 0.25μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured. Results: Vitamin D deficiency and insufficiency were associated with increased severity and unfavourable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ and MPO in the lung, as well as down-regulation of proinflammatory pathways. Conclusion: Normal levels of endogenous Vitamin D are associated with reduced severity and risk of unfavourable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.
Statement of Ethics The SAVE trial (EudraCT number 2020-001466-11; ClinicalTrials.gov registration NCT04357366) was approved by the National Ethics Committee of Greece (approval 38/20) and by the National Organization for Medicines of Greece (approval ISO 28/20). The ESCAPE trial (EudraCT number 2020-001039-29; Clinicaltrials.gov NCT04339712) was approved by the National Ethics Committee of Greece (approval 30/20) and by the National Organization for Medicines of Greece (approval IS 021-20). Not mechanically ventilated patients were enrolled after written informed consent provided by themselves. Patients under mechanical ventilation were enrolled after written informed consent provided by their legal representative. Animal experiments were conducted in the Unit of Animals for Medical and Scientific purposes of the University General Hospital "Attikon" (Athens, Greece). All experiments were licensed from the Greek veterinary directorate under the protocol numbers 471955/06.07.2020 and 846137/07.07.2023.
Conflict of Interest Statement EJG-B has received honoraria from Abbott Products Operations AG, bioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and Xbiotech Inc; independent educational grants from Abbott CH, bioMérieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and UCB; and funding from the Horizon2020 Marie Skłodowska-Curie International Training Network "the European Sepsis Academy" (granted to the National and Kapodistrian University of..
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