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Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients

Daneshkhah et al., Aging Clinical and Experimental Research, doi:10.1007/s40520-020-01677-y
Sep 2020  
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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 81 treatments. c19early.org
Retrospective ecological study of vitamin D levels and COVID-19 mortality in 9 countries suggesting a possible association between lower population vitamin D levels and higher COVID-19 mortality. Authors use national vitamin D data and perform regression analysis showing a correlation between lower vitamin D levels and higher mortality based on time-adjusted case mortality ratios.
Daneshkhah et al., 2 Sep 2020, retrospective, Italy, peer-reviewed, mean age 56.0, 6 authors, study period 1 April, 2020 - 7 April, 2020. Contact: v-backman@northwestern.edu.
This PaperVitamin DAll
Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients
Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman
Aging Clinical and Experimental Research, doi:10.1007/s40520-020-01677-y
Objectives We present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients. Design The time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL. Results A link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD's possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion We conclude that future studies on VitD's role in reducing cytokine storm and COVID-19 mortality are warranted.
Conflict of interest On behalf of all authors, the corresponding author states that there is no conflict of interest. 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 give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ethical approval
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The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated ' 'mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 ' 'was used to determine countries with similar screening strategies. A possible association of ' 'A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in ' 'countries with similar screening strategy was investigated. We considered high C-reactive ' 'protein (CRP) in severe COVID-19 patients (CRP\u2009≥\u20091\xa0mg/dL) as a surrogate of a ' 'cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as ' 'hs-CRP\u2009≥\u20090.2\xa0mg/dL.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>A link between 25(OH)D and A-CMR in countries with similar screening ' 'strategy is evidence for VitD’s possible role in reducing unregulated cytokine production and ' 'inflammation among patients with severe COVID-19. 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' 'https://www.gov.uk/government/statistics/ndns-results-from-years-5-and-6-combined. ' 'Accessed 26 Apr 2020'}, { 'key': '1677_CR65', 'doi-asserted-by': 'publisher', 'first-page': '203', 'DOI': '10.1038/ejcn.2009.140', 'volume': '64', 'author': 'RD Semba', 'year': '2010', 'unstructured': 'Semba RD, Houston DK, Bandinelli S et al (2010) Relationship of ' '25-hydroxyvitamin D with all-cause and cardiovascular disease mortality ' 'in older community-dwelling adults. Eur J Clin Nutr 64:203–209. ' 'https://doi.org/10.1038/ejcn.2009.140', 'journal-title': 'Eur J Clin Nutr'}, { 'key': '1677_CR66', 'first-page': '644', 'volume': '48', 'author': 'DD Farhud', 'year': '2019', 'unstructured': 'Farhud DD, Mehrabi A, Sarafnejad A et al (2019) A comprehensive, ' 'epidemiological and ecological descriptive study on vitamin d status in ' 'Iran (308005 People, from 2009–2018). 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' 'https://doi.org/10.1159/000047075', 'journal-title': 'Biol Neonate'}, { 'key': '1677_CR100', 'unstructured': 'World first coronavirus treatment approved for NHS use by government. ' 'In: GOV.UK. ' 'https://www.gov.uk/government/news/world-first-coronavirus-treatment-approved-for-nhs-use-by-government. ' 'Accessed 18 Jun 2020'}, { 'key': '1677_CR101', 'doi-asserted-by': 'publisher', 'first-page': 'e832', 'DOI': '10.1542/peds.2012-3986', 'volume': '132', 'author': 'AR Aluisio', 'year': '2013', 'unstructured': 'Aluisio AR, Maroof Z, Chandramohan D et al (2013) Vitamin D3 ' 'supplementation and childhood diarrhea: a randomized controlled trial. 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