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All Studies   Meta Analysis    Recent:   

Vitamin D modulates systemic inflammation in patients with severe COVID-19

Saheb Sharif-Askari et al., Life Sciences, doi:10.1016/j.lfs.2022.120909
Aug 2022  
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ICU time 36% Improvement Relative Risk Vitamin D  Saheb Sharif-Askari et al.  ICU PATIENTS Is very late treatment with vitamin D beneficial for COVID-19? Retrospective 45 patients in the USA Shorter ICU admission with vitamin D (p=0.01) c19early.org Saheb Sharif-Askari et al., Life Scien.., Aug 2022 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
Retrospective 20 ICU patients treated with vitamin D in the UAE, and 25 matched controls, showing significantly shorter ICU stay with treatment. Lower proinflammatory cytokines were associated with lower severity markers. Authors also perform a PBMC In Vitro study, with both the clinical and in vitro studies showing vitamin D attenuated major proinflammatory signaling pathways.
Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 69% [47‑82%] lower risk vs. 39% [27‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.
This is the 94th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
This study is excluded in the after exclusion results of meta analysis: very late stage study using cholecalciferol instead of calcifediol or calcitriol.
ICU time, 35.7% lower, relative time 0.64, p = 0.01, treatment 20, control 25.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Saheb Sharif-Askari et al., 24 Aug 2022, retrospective, USA, peer-reviewed, 10 authors, dosage 50,000IU days 1, 8, 15. Contact: rhalwani@sharjah.ac.ae.
This PaperVitamin DAll
Vitamin D modulates systemic inflammation in patients with severe COVID-19
Fatemeh Saheb Sharif-Askari, Shirin Hafezi, Narjes Saheb Sharif-Askari, Hawra Ali Hussain Alsayed, Bushra Mdkhana, Balachandar Selvakumar, Mohamad-Hani Temsah, Basema Saddik, Fatme Al Anouti, Rabih Halwani
Life Sciences, doi:10.1016/j.lfs.2022.120909
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
References
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Caunt, Keyse, Dual-specificity MAP kinase phosphatases (MKPs), The FEBS Journal, doi:10.1111/j.1742-4658.2012.08716.x
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Chauss, Freiwald, Mcgregor, Yan, Wang et al., Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells, Nature Immunology, doi:10.1038/s41590-021-01080-3
Chen, Hsieh, Wu, Lin, Chen, Dihydroxyvitamin D3
Chen, Yu, Fu, Wang, Chen et al., Vitamin D3 inhibits lipopolysaccharideinduced placental inflammation through reinforcing interaction between vitamin D receptor and nuclear factor kappa B p65 subunit, Scientific Reports, doi:10.1038/srep10871
Cron, Caricchio, Chatham, Calming the cytokine storm in COVID-19, Nature Medicine, doi:10.1038/s41591-021-01500-9
Dauletbaev, Herscovitch, Das, Chen, Bernier et al., Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1, British Journal of Pharmacology, doi:10.1111/bph.13249
Gharibi, Babaloo, Hosseini, Abdollahpour-Alitappeh, Hashemi et al., Targeting STAT3 in cancer and autoimmune diseases, European Journal of Pharmacology, doi:10.1016/j.ejphar.2020.173107
Goel, Sharif-Askari, Sharif-Askari, Mdkhana, Mahboub et al., SARS-CoVexpression, Frontiers in Pharmacology
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Maghbooli, Sahraian, Jamalimoghadamsiahkali, Asadi, Zarei et al., Treatment With 25-Hydroxyvitamin D<sub>3</sub> (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial, Endocrine Practice, doi:10.1016/j.eprac.2021.09.016
Mahmudpour, Roozbeh, Keshavarz, Farrokhi, Nabipour, COVID-19 cytokine storm: The anger of inflammation, Cytokine, doi:10.1016/j.cyto.2020.155151
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Muhammad, Sharif-Askari, Cui, Hamad, Halwani, SARS-CoV-2 Infection-Induced Promoter Hypomethylation as an Epigenetic Modulator of Heat Shock Protein A1L (HSPA1L) Gene, Frontiers in Genetics, doi:10.3389/fgene.2021.622271
Muthian, Raikwar, Rajasingh, Bright, 1,25 dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNγ axis leading to Th1 response in experimental allergic encephalomyelitis, Journal of Neuroscience Research, doi:10.1002/jnr.20826
Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study), Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139065
Sharif-Askari, Sharif-Askari, Goel, Hafezi, Assiri et al., SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway, European Journal of Pharmacology, doi:10.1016/j.ejphar.2021.174374
Zugowski, Lieder, Müller, Gasch, Corvinus et al., STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter, doi:10.1515/bc.2011.038
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Late treatment
is less effective
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