Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?
et al., Neuroimmunomodulation, doi:10.1159/000533286, Aug 2023
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 126 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
Review of the potential benefits of vitamin D for COVID-19 in relation to neuroprotection. Authors note that neurological symptoms are common in COVID-19, likely related to disruption of the blood-brain barrier, inflammation, and immunothrombosis (clotting). Vitamin D could help protect the integrity of the blood-brain barrier and reduce neuroinflammation. In vitro and animal studies show vitamin D reduces inflammatory cytokine production, shifts microglia to an anti-inflammatory phenotype, promotes myelination, and has antioxidant effects in the brain, which suggests a neuroprotective role. Note that lumisterol and tachysterol are created via sun exposure. Vitamin D supplementation can provide the active calcitriol metabolite with direct anti-inflammatory and immunomodulatory effects, however supplementation alone will not provide the active hydroxylated metabolites of lumisterol and tachysterol that come from sun exposure. Sun exposure may provide additional immune benefits.
1.
Jaurrieta-Largo et al., A Machine Learning Approach to Understanding the Genetic Role in COVID-19 Prognosis: The Influence of Gene Polymorphisms Related to Inflammation, Vitamin D, and ACE2, International Journal of Molecular Sciences, doi:10.3390/ijms26167975.
2.
Al-Khrasani et al., Do vitamins halt the COVID-19-evoked pro-inflammatory cytokines involved in the development of neuropathic pain?, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2025.118346.
3.
Kow et al., Vitamin D and COVID‐19: How much more evidence do we need?, Nutrition in Clinical Practice, doi:10.1002/ncp.11349.
4.
Bigman et al., A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery, Nutrients, doi:10.3390/nu17111802.
5.
Hewison, M., COVID-19 and our understanding of vitamin D and immune function, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2025.106710.
6.
Wimalawansa, S., Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review, Nutrients, doi:10.3390/nu17030599.
7.
Sanduzzi Zamparelli et al., Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective, Life, doi:10.3390/life15010113.
8.
Fazli et al., Possible Link between Gut Microbiota, Diet, and COVID-19 Infection, Journal of Medical Bacteriology, 12:4, jmb.tums.ac.ir/index.php/jmb/article/view/525.
9.
Wojciulik et al., The impact of genetic polymorphism on course and severity of the SARS-CoV-2 infection and COVID-19 disease, Przeglad Epidemiologiczny, doi:10.32394/pe/194862.
10.
Wimalawansa (B), S., Unveiling the Interplay—Vitamin D and ACE-2 Molecular Interactions in Mitigating Complications and Deaths from SARS-CoV-2, Biology, doi:10.3390/biology13100831.
11.
Santa et al., Comparative analysis of COVID-19 responses in Japan and Africa: diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality—A systematic review and meta-analysis, Frontiers in Nutrition, doi:10.3389/fnut.2024.1465324.
12.
Kaushal, A., Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections, Journal of Translational Medicine, doi:10.1186/s12967-024-05587-9.
13.
Mu et al., Anti-inflammatory and Nutritional Interventions Against SARS-CoV-2: A Comprehensive Review, Journal of Agriculture and Food Research, doi:10.1016/j.jafr.2024.101422.
14.
Wimalawansa (C), S., Unlocking Insights: Navigating COVID-19 Challenges and Emulating Future Pandemic Resilience Strategies with Strengthening Natural Immunity, Heliyon, doi:10.1016/j.heliyon.2024.e34691.
15.
Imran et al., Therapeutic Role of Vitamin D in COVID-19 Patients, Clinical Nutrition Open Science, doi:10.1016/j.nutos.2024.07.004.
16.
Grant, W., Vitamin D and viral infections: Infectious diseases, autoimmune diseases, and cancers, Advances in Food and Nutrition Research, doi:10.1016/bs.afnr.2023.12.007.
17.
Polonowita et al., Molecular Quantum and Logic Process of Consciousness—Vitamin D Big-Data in COVID-19—A Case for Incorporating Machine Learning In Medicine, European Journal of Biomedical and Pharmaceutical sciences, doi:10.5281/zenodo.10435649.
18.
Gomaa et al., Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy, Inflammopharmacology, doi:10.1007/s10787-023-01383-x.
19.
Gotelli et al., Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?, Neuroimmunomodulation, doi:10.1159/000533286.
20.
Cutolo et al., Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19, Nature Reviews Rheumatology, doi:10.1038/s41584-023-00944-2.
21.
Schloss et al., Nutritional deficiencies that may predispose to long COVID, Inflammopharmacology, doi:10.1007/s10787-023-01183-3.
22.
Arora et al., Global Dietary and Herbal Supplement Use during COVID-19—A Scoping Review, Nutrients, doi:10.3390/nu15030771.
23.
Nicoll et al., COVID-19 Prevention: Vitamin D Is Still a Valid Remedy, Journal of Clinical Medicine, doi:10.3390/jcm11226818.
24.
Foshati et al., Antioxidants and clinical outcomes of patients with coronavirus disease 2019: A systematic review of observational and interventional studies, Food Science & Nutrition, doi:10.1002/fsn3.3034.
25.
Quesada-Gomez et al., Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol, Nutrients, doi:10.3390/nu14132716.
26.
DiGuilio et al., Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy, International Journal of Molecular Sciences, doi:10.3390/ijms23062995.
27.
Grant (B) et al., A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health, Nutrients, doi:10.3390/nu14030639.
28.
Shah Alam et al., The role of vitamin D in reducing SARS-CoV-2 infection: An update, International Immunopharmacology, doi:10.1016/j.intimp.2021.107686.
29.
Griffin et al., Perspective: Vitamin D supplementation prevents rickets and acute respiratory infections when given as daily maintenance but not as intermittent bolus: implications for COVID-19, Clinical Medicine, doi:10.7861/clinmed.2021-0035.
30.
Kohlmeier et al., When Mendelian randomisation fails, BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000265.
31.
Brenner, H., Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths—Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action, Nutrients, doi:10.3390/nu13020411.
32.
Mercola et al., Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity, Nutrients 2020, 12:11, 3361, doi:10.3390/nu12113361.
33.
Basha et al., Is the shielding effect of cholecalciferol in SARS CoV-2 infection dependable? An evidence based unraveling, Clinical Epidemiology and Global Health, doi:10.1016/j.cegh.2020.10.005.
34.
Xu et al., The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19, Journal of Translational Medicine, doi:10.1186/s12967-020-02488-5.
35.
Alexander et al., Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19, Nutrients, doi:10.3390/nu12082358.
36.
Andrade et al., Vitamin A and D deficiencies in the prognosis of respiratory tract infections: A systematic review with perspectives for COVID-19 and a critical analysis on supplementation, SciELO preprints, doi:10.1590/SciELOPreprints.839.
37.
Grant (C) et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients, 12:4, 988, doi:10.3390/nu12040988.
38.
McCullough et al., Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2018.12.010.
39.
EFSA, Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular function (ID 159) pursuant to Article 13(1) of Regulation (E, EFSA Journal, doi:10.2903/j.efsa.2010.1468.
40.
EFSA (B), Scientific Opinion on the substantiation of a health claim related to vitamin D and contribution to the normal function of the immune system pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2015.4096.
Gotelli et al., 9 Aug 2023, peer-reviewed, 10 authors.
Contact: emanuele.gotelli@live.it, stefano.soldano@unige.it, elvis.hysa@gmail.com, andrea.casabella@hsanmartino.it, andrea.cere00@gmail.com, carmen.pizzorni@unige.it, sabrina.paolino@unige.it, albertosulli@unige.it, vanessa.smith@ugent.be, mcutolo@unige.it.
Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?
Neuroimmunomodulation, doi:10.1159/000533286
yet assigned to an issue. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to the content.
Conflict of Interest Statement The Authors have no conflicts of interest to declare. VS is a senior clinical investigator of the Research Foundation -Flanders (Belgium) (FWO) (1.8.029.20N). The FWO was not involved in study design, collection, analysis and interpretation of data, writing of the report, nor in the decision to submit the article for publication.
Author Contributions EG and MC conceptualized the review, collecting data and writing the manuscript. SS created all the figures. SS, A Casabella, EH, A Cere, CP, SP, AS and VS revised the manuscript for important intellectual content. All Authors agreed to the content of the review and are accountable for all aspects of accuracy and integrity. All Authors read and agreed to the current version of the manuscript.
References
Aghagoli, Gallo Marin, Katchur, Chaves-Sell, Asaad et al., Neurological Involvement in COVID-19 and Potential Mechanisms: A Review, Neurocrit Care
Ali, Shah, Zaman, Uddin, Khan et al., Vitamin D exerts neuroprotection via SIRT1/nrf-2/NF-kB signaling pathways against D-galactose-induced memory impairment in adult mice, Neurochem Int
Anvari, Fateh, Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID-19 patients according to different SARS-CoV-2 variants. Sci Rep
Bhutia, Vitamin D in autophagy signaling for health and diseases: Insights on potential mechanisms and future perspectives, J Nutr Biochem
Bonaventura, Vecchié, Dagna, Martinod, Dixon et al., Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19, Nat Rev Immunol
Buendia, Michalska, Navarro, Gameiro, Egea et al., Nrf2-ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases, Pharmacol Ther
Carvelli, Demaria, Vély, Batista, Benmansour et al., Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis, Nature
Ceolin, Mano, Hames, Antunes, Brietzke et al., Vitamin D, Depressive Symptoms, and Covid-19 Pandemic, Front Neurosci
Charoenngam, Jaroenlapnopparat, Mettler, Grover, Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence, Biomedicines
Chauss, Freiwald, Mcgregor, Yan, Wang et al., Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells, Nat Immunol
Chen, Haupert, Zimmermann, Shi, Fritsche et al., Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review, J Infect Dis
Chen, Weng, Zhang, Wang, Lu et al., Low-Dose Vitamin D Protects Hyperoxia-Induced Bronchopulmonary Dysplasia by Inhibiting Neutrophil Extracellular Traps. Front Pediatr
Chen, Zhu, Chen, Zuo, Zhang et al., 1,25-Dihydroxyvitamin D3 preserves intestinal epithelial barrier function from TNF-α induced injury via suppression of NF-kB p65 mediated MLCK-P-MLC signaling pathway, Biochem Biophys Res Commun
Chiodini, Gatti, Soranna, Merlotti, Mingiano et al., Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes
Chou, Beghi, Helbok, Moro, Sampson et al., Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19-A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium, JAMA Netw Open
Cimmino, Morello, Conte, Pellegrino, Marra et al., Vitamin D inhibits Tissue Factor and CAMs expression in oxidized low-density lipoproteins-treated human endothelial cells by modulating NF-κB pathway, Eur J Pharmacol
Cui, Lu, Wang, Wang, Zhang et al., Microglia/macrophages require vitamin D signaling to restrain neuroinflammation and brain injury in a murine ischemic stroke model, J Neuroinflammation
Cui, Xu, Li, Qiao, Han et al., Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of reninangiotensin system, Redox Biol
Cutolo, Paolino, Smith, Evidences for a protective role of vitamin D in COVID-19. RMD Open
Cutolo, Smith, Paolino, Gotelli, Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19, Nat Rev Rheumatol
Cutolo, Smith, Paolino, Understanding immune effects of oestrogens to explain the reduced morbidity and mortality in female versus male COVID-19 patients. Comparisons with autoimmunity and vaccination, Clin Exp Rheumatol
Cutolo, Sulli, Smith, Gotelli, Emerging nailfold capillaroscopic patterns in COVID-19: from acute patients to survivors, Reumatismo
Di Filippo, Frara, Nannipieri, Cotellessa, Locatelli et al., Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors, J Clin Endocrinol Metab
Di Filippo, Uygur, Locatelli, Nannipieri, Frara et al., Low vitamin D levels predict outcomes of COVID-19 in patients with both severe and non-severe disease at hospitalization, Endocrine
Dobrijevic, Robajac, Gligorijevic, Šunderic, Penezic et al., The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with COVID-19 severity: A systematic review and metaanalysis, EXCLI J
Erickson, Rhea, Knopp, Banks, Interactions of SARS-CoV-2 with the Blood-Brain Barrier, Int J Mol Sci
Feige, Moser, Bieler, Schwenker, Hauer et al., Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats, Nutrients
Gilani, Bin-Jumah, Nadeem, Kazmi, Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy, Expert Rev Anti Infect Ther
Gotelli, Soldano, Hysa, Paolino, Campitiello et al., Vitamin D and COVID-19: Narrative Review after 3 Years of Pandemic, Nutrients
Groves, Burne, The impact of vitamin D deficiency on neurogenesis in the adult brain, Neural Regen Res
Guo, Wang, Yin, Microglia Polarization From M1 to M2 in Neurodegenerative Diseases. Front Aging Neurosci
Harapan, Yoo, Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 19 (COVID-19), J Neurol
Hernández-Parra, Hernández, Figueroa-González, Carmen, González-Torres et al., Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain, Front Cell Neurosci
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab
Huang, Hussain, Chang, Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms, CNS Neurosci Ther
Jiang, Yang, Wang, Zhou, Vitamin D Protects against Traumatic Brain Injury via Modulating TLR4/MyD88/NF-κB Pathway-Mediated Microglial Polarization and Neuroinflammation, Biomed Res Int
Jiao, Li, Lv, Jv, He, Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats, Neuroreport
Jolliffe, Camargo, Jr, Sluyter, Aglipay et al., Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials, Lancet Diabetes Endocrinol
Ketha, Thacher, Oberhelman, Fischer, Singh et al., Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio. Bone
Lamers, Haagmans, SARS-CoV-2 pathogenesis, Nat Rev Microbiol
Lawrence, Schardien, Wigdahl, Nonnemacher, Roles of neuropathology-associated reactive astrocytes: a systematic review, Acta Neuropathol Commun
Li, Yao, Liu, Zhu, Lam et al., Vitamin D Promotes Remyelination by Suppressing and Inducing Oligodendrocyte Precursor Cell Differentiation after Traumatic Spinal Cord Injury, Int J Biol Sci
Liu, Zhang, Joo, Sun, NF-κB signaling in inflammation, Signal Transduct Target Ther
Malik, Acharya, Avedissian, Byrareddy, Fletcher et al., ACE-2, TMPRSS2, and Neuropilin-1 Receptor Expression on Human Brain Astrocytes and Pericytes and SARS-CoV-2 Infection Kinetics, Int J Mol Sci
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Matschke, Lütgehetmann, Hagel, Sperhake, Schröder et al., Neuropathology of patients with COVID-19 in Germany: a post-mortem case series, Lancet Neurol
Miller, Mcgrath, Hu, Ariannejad, Weston et al., Coronavirus interactions with the cellular autophagy machinery, Autophagy
Monje, Iwasaki, The neurobiology of long COVID, Neuron
Montiel, Lobysheva, Gérard, Vermeersch, Perez-Morga et al., Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients, EBioMedicine
Mukerji, Solomon, What can we learn from brain autopsies in COVID-19?, Neurosci Lett
Nannoni, De Groot, Bell, Markus, Stroke in COVID-19: A systematic review and meta-analysis, Int J Stroke
Nielsen, Junker, Boelt, Cohen, Munger et al., Vitamin D status and severity of COVID-19. Sci Rep
Ohsawa, Koyama, Yamamoto, Hirosawa, Kamei et al., 1alpha,25-dihydroxyvitamin D(3) and its potent synthetic analogs downregulate tissue factor and upregulate thrombomodulin expression in monocytic cells, counteracting the effects of tumor necrosis factor and oxidized LDL, Circulation
Ortatatli, Fatsa, Mulazimoglu, Oren, Artuk et al., Role of Vitamin D, ACE2 and the Proteases as TMPRSS2 and Furin on SARS-CoV-2 Pathogenesis and COVID-19 Severity, Arch Med Res
Pereira, Damascena, Azevedo, De Almeida Oliveira, Da et al., Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis, Crit Rev Food Sci Nutr
Qayyum, Mohammad, Slominski, Hassan, Tuckey et al., Vitamin D and lumisterol novel metabolites can inhibit SARS-CoV-2 replication machinery enzymes, Am J Physiol Endocrinol Metab
Qayyum, Slominski, Raman, Slominski, Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19, Nutrients
Reichrath, März, De Gruijl, Vieth, Grant et al., An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act, Anticancer Res
Scialo, Amato, Pastore, Matera, Cazzola, ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung
Slominski, Kim, Li, Postlethwaite, Tieu et al., Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. Sci Rep
Slominski, Kim, Slominski, Song, Janjetovic et al., Metabolic activation of tachysterol3 to biologically active hydroxyderivatives that act on VDR, AhR, LXRs, and PPARγ receptors, FASEB J
Slominski, Stefan, Athar, Holick, Jetten et al., COVID-19 and Vitamin D: A lesson from the skin, Exp Dermatol
Song, Qayyum, Greer, Slominski, Raman et al., Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study, J Biomol Struct Dyn
Stein, Ramelli, Grazioli, Chung, Singh et al., SARS-CoV-2 infection and persistence in the human body and brain at autopsy, Nature
Sulli, Gotelli, Bica, Schiavetti, Pizzorni et al., Detailed videocapillaroscopic microvascular changes detectable in adult COVID-19 survivors, Microvasc Res
Sulli, Gotelli, Casabella, Paolino, Pizzorni et al., Vitamin D Lung Outcomes in Elderly COVID-19 Patients, Nutrients
Tay, Yeap, Dalan, Wong, Hou, Increased monocyte-platelet aggregates and monocyteendothelial adhesion in healthy individuals with vitamin D deficiency, FASEB J
Thakur, Miller, Glendinning, Al-Dalahmah, Banu et al., COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital, Brain
Vanderheiden, Klein, Neuroinflammation and COVID-19, Curr Opin Neurobiol
Wang, Nestel, Bourdeau, Nagai, Wang et al., Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression, J Immunol
Yang, Kern, Losada, Agam, Maat et al., Dysregulation of brain and choroid plexus cell types in severe COVID-19, Nature
Zhu, Chen, Liu, NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond, Front Immunol
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"abstract": "<jats:p>Calcitriol and hydroxyderivatives of lumisterol and tachisterol are secosteroid hormones with immunomodulatory and anti-inflammatory properties. Since the beginning of the COVID-19 pandemic, several studies have correlated deficient serum concentrations of vitamin D3 (calcifediol) with increased severity of the course of SARS-CoV-2 infection. Among systemic complications, subjective (anosmia, ageusia, depression, dizziness) and objective (ischemic stroke, meningo-encephalitis, myelitis, seizures, Guillain-Barré syndrome) neurological symptoms have been reported in up to 80% of severe COVID-19 patients. In this narrative review we will resume the pathophysiology of SARS-CoV-2 infection and the mechanisms of acute and chronic neurological damage. SARS-CoV-2 can disrupt the integrity of the endothelial cells of the blood-brain barrier to enter the nervous central system. Invasion of pro-inflammatory cytokines and polarization of astrocytes and microglia cells always in a pro-inflammatory sense together with the pro-coagulative phenotype of cerebral endothelial vessels in response to both SARS-CoV-2 and immune cells invasion (immunothrombosis) are the major drivers of neuro-damage. Calcitriol and hydroxyderivatives of lumisterol and tachisterol could play an adjuvant role in neuroprotection, through mitigation of neuroinflammation and protection of endothelial integrity of the blood-brain barrier. Dedicated studies on this topic are currently lacking and are desirable to confirm the link between vitamin D3 and neuroprotection in COVID-19 patients.</jats:p>",
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