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Randomized trial of influence of vitamin D on the prevention and improvement of symptomatic COVID-19

Wang et al., Scientific Reports, doi:10.1038/s41598-024-66267-8 (date from preprint), NCT05673980
Mar 2023  
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Progression, combined sy.. 25% treatment Improvement Relative Risk Progression, fever -4% treatment Progression, sore throat 8% treatment Progression, rhinorrhea or.. 42% treatment Progression, diarrhea 66% treatment Progression, vomiting 66% treatment Progression, cough 13% treatment Progression, muscle/joint.. 48% treatment Progression, taste/smell -56% treatment Case 4% treatment Case, first two weeks -15% treatment Case, last two weeks 48% treatment Time to viral- 11% no CI Case, >30ng/ml vs. ≤20ng.. 23% levels Vitamin D  Wang et al.  Prophylaxis  RCT Is prophylaxis with vitamin D beneficial for COVID-19? RCT 202 patients in China (December 2022 - February 2023) Lower progression with vitamin D (not stat. sig., p=0.15) c19early.org Wang et al., Scientific Reports, March 2023 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.
5,100+ studies for 109 treatments. c19early.org
RCT 214 low risk (no hospitalization) healthcare workers in China, showing no significant differences with vitamin D2 prophylaxis using two bolus treatments.
Patients with higher vitamin D levels (across both groups) were less likely to be infected. The trial only lasted one month. Two thirds of the cases occurred within the first week, when treatment may have minimal impact on vitamin D levels (calcifediol or calcidiol may be more effective due to delays in conversion).
Cases were lower in the intervention group during the last two weeks, after treatment is likely to have increased levels significantly. Regular rather than bolus treatment, longer term treatment, or alternative forms of vitamin D (e.g., calcifediol/calcidiol) may be more effective.
Authors report that "4.5% of subjects were lost to follow-up" (1% and 7.6% per group). Figure 2 shows 2 and 0 patients at risk at day 28. This is inconsistent with the reported infection rates and loss to followup, raising concern for the validity of the data.
There are conflicting results in the preprint1. Authors reported 50% cases in the vitamin D2 group and 54% control, while the journal version has different numbers without explanation.
The study was registered retrospectively. There was no mortality or hospitalization. 200,000 IU vitamin D2 fortnightly.
This is the 27th of 30 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000032.
This is the 109th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
risk of progression, 25.2% lower, RR 0.75, p = 0.15, treatment 99, control 103, combined symptoms.
risk of progression, 4.0% higher, RR 1.04, p = 1.00, treatment 5 of 99 (5.1%), control 5 of 103 (4.9%), risk of severe case, fever.
risk of progression, 7.5% lower, RR 0.92, p = 1.00, treatment 8 of 99 (8.1%), control 9 of 103 (8.7%), NNT 152, risk of severe case, sore throat.
risk of progression, 42.2% lower, RR 0.58, p = 0.41, treatment 5 of 99 (5.1%), control 9 of 103 (8.7%), NNT 27, risk of severe case, rhinorrhea or congestion.
risk of progression, 66.2% lower, RR 0.34, p = 1.00, treatment 0 of 99 (0.0%), control 1 of 103 (1.0%), NNT 103, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), risk of severe case, diarrhea.
risk of progression, 66.2% lower, RR 0.34, p = 1.00, treatment 0 of 99 (0.0%), control 1 of 103 (1.0%), NNT 103, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), risk of severe case, vomiting.
risk of progression, 13.3% lower, RR 0.87, p = 0.82, treatment 10 of 99 (10.1%), control 12 of 103 (11.7%), NNT 65, risk of severe case, cough.
risk of progression, 48.0% lower, RR 0.52, p = 0.13, treatment 8 of 99 (8.1%), control 16 of 103 (15.5%), NNT 13, risk of severe case, muscle/joint aches.
risk of progression, 56.1% higher, RR 1.56, p = 0.68, treatment 3 of 99 (3.0%), control 2 of 103 (1.9%), risk of severe case, taste/smell.
risk of case, 3.7% lower, RR 0.96, p = 0.89, treatment 50 of 99 (50.5%), control 54 of 103 (52.4%), NNT 52.
risk of case, 15.0% higher, RR 1.15, p = 0.47, treatment 42 of 99 (42.4%), control 38 of 103 (36.9%), first two weeks.
risk of case, 48.0% lower, RR 0.52, p = 0.13, treatment 8 of 99 (8.1%), control 16 of 103 (15.5%), NNT 13, last two weeks.
time to viral-, 10.8% lower, relative time 0.89, treatment 99, control 103.
risk of case, 22.7% lower, RR 0.77, p = 0.19, high D levels (≥30ng/ml) 20 of 44 (45.5%), low D levels (<20ng/ml) 50 of 85 (58.8%), NNT 7.5, outcome based on serum levels.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wang et al., 29 Mar 2023, Randomized Controlled Trial, China, peer-reviewed, median age 36.5, 23 authors, study period 18 December, 2022 - 20 February, 2023, dosage 200,000IU days 1, 14, trial NCT05673980 (history). Contact: schl@bjmu.edu.cn, lianglbh@126.com, haiyanli1027@hotmail.com.
This PaperVitamin DAll
Influence of a High Vitamin D2 Dose on the Prevention and Improvement of Symptomatic COVID-19 in Health Care Workers: A Multicenter Randomized Clinical Trial
Huan Wang, PhD Liyuan Tao, Liyan Cui, Yahong Chen, Dongyang Liu, Lixiang Xue, Yuping Yang, Yang Lv, Fuchun Zhang, Tiancheng Wang, Xiaoxiao Wang, Wanqiong Yuan, Hao Liu, Jie Huang, Yanfang Jiang, Na Liu, Lijuan Yang, Yunjing Hu, Yanfang Li, Yuling Gao, Dr Haiyan Li, Baohua Li, PhD Chun-Li Song
Background COVID-19 pandemic exacerbates infections among health care workers, highlighting importance of prevention for these high-risk people. Vitamin D, as an immunomodulator, is thought likely to be to correlate with the inflammatory reaction. Methods This was a multicenter, open-label, randomized controlled trial. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to 200, 000 IU vitamin D2 fortnightly or non-intervention at a ratio 1:1. PCR or antigen tests were taken at baseline and twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines (IL-1β, IFN-α, IFN-
Article Information Corresponding Author: Chunli Song, Baohua Li, Haiyan Li This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4401710 P r e p r i n t n o t p e e r r e v i e w e d Conflict of Interest Disclosures: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Med.'}, { 'key': '66267_CR24', 'doi-asserted-by': 'publisher', 'first-page': '193', 'DOI': '10.1016/j.metabol.2018.12.010', 'volume': '92', 'author': 'A Bassatne', 'year': '2019', 'unstructured': 'Bassatne, A., Chakhtoura, M., Saad, R. & Fuleihan, G. E. Vitamin D ' 'supplementation in obesity and during weight loss: A review of ' 'randomized controlled trials. Metabolism. 92, 193–205 (2019).', 'journal-title': 'Metabolism.'}, { 'key': '66267_CR25', 'doi-asserted-by': 'publisher', 'first-page': '328', 'DOI': '10.3390/nu9040328', 'volume': '9', 'author': 'G Jean', 'year': '2017', 'unstructured': 'Jean, G., Souberbielle, J. C. & Chazot, C. Vitamin D in chronic kidney ' 'disease and dialysis patients. Nutrients. 9, 328 (2017).', 'journal-title': 'Nutrients.'}, { 'key': '66267_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1578', 'DOI': '10.1093/ajcn/nqy378', 'volume': '109', 'author': 'Z Malihi', 'year': '2019', 'unstructured': 'Malihi, Z. et al. Monthly high-dose vitamin D supplementation does not ' 'increase kidney stone risk or serum calcium: Results from a randomized ' 'controlled trial. Am. J. Clin. Nutr. 109, 1578–1587 (2019).', 'journal-title': 'Am. J. Clin. Nutr.'}, { 'key': '66267_CR27', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.ppat.1008874', 'volume': '16', 'author': 'M Mohan', 'year': '2020', 'unstructured': 'Mohan, M., Cherian, J. J. & Sharma, A. Exploring links between vitamin D ' 'deficiency and COVID-19. PLoS Pathog. 16, e1008874 (2020).', 'journal-title': 'PLoS Pathog.'}], 'container-title': 'Scientific Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41598-024-66267-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-024-66267-8', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41598-024-66267-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 9, 3]], 'date-time': '2024-09-03T20:28:38Z', 'timestamp': 1725395318000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41598-024-66267-8'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 9, 3]]}, 'references-count': 27, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['66267'], 'URL': 'http://dx.doi.org/10.1038/s41598-024-66267-8', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.21203/rs.3.rs-4128200/v1', 'asserted-by': 'object'}]}, 'ISSN': ['2045-2322'], 'subject': [], 'container-title-short': 'Sci Rep', 'published': {'date-parts': [[2024, 9, 3]]}, 'assertion': [ { 'value': '19 March 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '1 July 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '3 September 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'The authors declare no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '20519'}
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