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Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?

Gotelli et al., Neuroimmunomodulation, doi:10.1159/000533286
Aug 2023  
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Vitamin D for COVID-19
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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.
Gotelli et al., 9 Aug 2023, peer-reviewed, 10 authors. Contact:,,,,,,,,,
This PaperVitamin DAll
Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?
MD Emanuele Gotelli, PhD Stefano Soldano, MD Elvis Hysa, PhD Andrea Casabella, Andrea Cere, MD Carmen Pizzorni, MD Sabrina Paolino, MD Alberto Sulli, MD Vanessa Smith, MD Maurizio Cutolo
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) ( 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.
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{ 'DOI': '10.1159/000533286', 'ISSN': ['1021-7401', '1423-0216'], 'URL': '', '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>', 'author': [ {'affiliation': [], 'family': 'Gotelli', 'given': 'Emanuele', 'sequence': 'first'}, {'affiliation': [], 'family': 'Soldano', 'given': 'Stefano', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Hysa', 'given': 'Elvis', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Casabella', 'given': 'Andrea', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Cere', 'given': 'Andrea', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Pizzorni', 'given': 'Carmen', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Paolino', 'given': 'Sabrina', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Sulli', 'given': 'Alberto', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Smith', 'given': 'Vanessa', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Cutolo', 'given': 'Maurizio', 'sequence': 'additional'}], 'container-title': 'Neuroimmunomodulation', 'container-title-short': 'Neuroimmunomodulation', 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2023, 8, 9]], 'date-time': '2023-08-09T21:01:27Z', 'timestamp': 1691614887000}, 'deposited': { 'date-parts': [[2023, 8, 9]], 'date-time': '2023-08-09T21:02:33Z', 'timestamp': 1691614953000}, 'indexed': {'date-parts': [[2023, 8, 10]], 'date-time': '2023-08-10T04:12:35Z', 'timestamp': 1691640755934}, 'is-referenced-by-count': 0, 'issued': {'date-parts': [[2023, 8, 9]]}, 'language': 'en', 'license': [ { 'URL': '', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2023, 8, 9]], 'date-time': '2023-08-09T00:00:00Z', 'timestamp': 1691539200000}}, { 'URL': '', 'content-version': 'tdm', 'delay-in-days': 0, 'start': { 'date-parts': [[2023, 8, 9]], 'date-time': '2023-08-09T00:00:00Z', 'timestamp': 1691539200000}}], 'link': [ { 'URL': '', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': '', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '127', 'original-title': [], 'prefix': '10.1159', 'published': {'date-parts': [[2023, 8, 9]]}, 'published-online': {'date-parts': [[2023, 8, 9]]}, 'publisher': 'S. Karger AG', 'reference-count': 0, 'references-count': 0, 'relation': {}, 'resource': {'primary': {'URL': ''}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Endocrine and Autonomic Systems', 'Neurology', 'Endocrinology', 'Immunology'], 'subtitle': [], 'title': 'Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in ' 'protecting against neurodamage?', 'type': 'journal-article'}
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