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Low serum levels of zinc and 25-hydroxyvitmain D as potential risk factors for COVID-19 susceptibility: a pilot case-control study

Ghanei et al., European Journal of Clinical Nutrition, doi:10.1038/s41430-022-01095-5
Mar 2022  
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Case 42% Improvement Relative Risk Vitamin D for COVID-19  Ghanei et al.  Sufficiency Are vitamin D levels associated with COVID-19 outcomes? Prospective study of 185 patients in Iran (March 2020 - January 2021) Fewer cases with higher vitamin D levels (not stat. sig., p=0.093) c19early.org Ghanei et al., European J. Clinical Nu.., Mar 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
Case control study with 90 COVID-19 cases and 95 matched controls in Iran, showing significantly lower vitamin D levels for cases.
This is the 126th of 199 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 835,162 vigintillion).
Study covers vitamin D and zinc.
risk of case, 42.1% lower, OR 0.58, p = 0.09, high D levels (≥20ng/ml) 58 of 90 (64.4%) cases, 72 of 95 (75.8%) controls, NNT 7.4, case control OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ghanei et al., 23 Mar 2022, prospective, Iran, peer-reviewed, 6 authors, study period 20 March, 2020 - 20 January, 2021.
This PaperVitamin DAll
Low serum levels of zinc and 25-hydroxyvitmain D as potential risk factors for COVID-19 susceptibility: a pilot case-control study
Esmat Ghanei, Moein Baghani, Hamideh Moravvej, Atefeh Talebi, Ayda Bahmanjahromi, Fahimeh Abdollahimajd
European Journal of Clinical Nutrition, doi:10.1038/s41430-022-01095-5
BACKGROUND AND AIMS: This study aimed to evaluate serum 25-hydroxyvitmain D and zinc levels in coronavirus disease 2019 patients in comparison to healthy subjects. METHODS: This was a single-center case-control study performed from March 20, 2020, to January 20, 2021, in Tehran, Iran. All patients diagnosed with COVID-19 based on a positive nasopharyngeal swab polymerase chain reaction (PCR) test were included in the case group. Controls were selected from patients referred for routine checkups who had a negative COVID-19 PCR test. Age, sex, marital and educational status, comorbidities, and serum 25-hydroxyvitmain D and zinc levels of patients were recorded. RESULTS: Ninety patients in the case group and 95 subjects in the control group who were sex and age-matched were studied. 25hydroxyvitmain D levels higher than 20 ng/ml were observed in 58 (64%) cases and 72 (76%) controls (P = 0.09). The median 25hydroxyvitmain D level in the case group was significantly lower than controls (26 (interquartile range [IQR] = 24) ng/ml vs. 38 (IQR = 22) ng/ml, respectively, P < 0.01). The median zinc level in the case group was 56 (IQR = 23) mcg/dL, while it was 110 (IQR = 27) mcg/dL among the controls (P < 0.01). There was no significant difference in the level of 25-hydroxyvitmain D and zinc between cases with and without comorbidities (P > 0.05). Susceptibility to SARS-CoV-2 infection could be predicted by serum 25hydroxyvitmain D levels below 25.2 ng/ml (81% sensitivity; 48% specificity) or zinc levels below 86.3 mcg/dL (93% sensitivity; 92% specificity). CONCLUSIONS: Low serum zinc and 25-hydroxyvitmain D levels appear to be risk factors for COVID-19 affliction; thus, the treatment of individuals with such deficiencies is recommended.
AUTHOR CONTRIBUTIONS EG and FA contributed to the conception of the work. HM, EG, MB, AB and FA contributed to the acquisition of data and AT contributed to the analysis, and interpretation of data for the work. AB, MB and FA drafted the manuscript. FA and EG and HM critically revised the manuscript. All authors gave final approval and agreed to be accountable for all aspects of the work ensuring integrity and accuracy. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. COMPETING INTERESTS The authors declare no competing interests. ETHICAL APPROVAL The study protocol was approved by our institute's Ethics Committee in Biomedical Research with reference code IR.SBMU.SRC.REC.1399.007. ADDITIONAL INFORMATION Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41430-022-01095-5. Correspondence and requests for materials should be addressed to Ayda bahmanjahromi or Fahimeh Abdollahimajd. Reprints and permission information is available at http://www.nature.com/ reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Nature 2005;435:374–9.', 'journal-title': 'Nature'}, { 'key': '1095_CR30', 'doi-asserted-by': 'publisher', 'first-page': '1712', 'DOI': '10.3389/fimmu.2020.01712', 'volume': '11', 'author': 'I Wessels', 'year': '2020', 'unstructured': 'Wessels I, Rolles B, Rink L. The potential impact of zinc ' 'supplementation on COVID-19 pathogenesis. Front Immunol. 2020;11:1712.', 'journal-title': 'Front Immunol'}, { 'key': '1095_CR31', 'doi-asserted-by': 'publisher', 'first-page': '343', 'DOI': '10.1016/j.ijid.2020.09.014', 'volume': '100', 'author': 'D Jothimani', 'year': '2020', 'unstructured': 'Jothimani D, Kailasam E, Danielraj S, Nallathambi B, Ramachandran H, ' 'Sekar P, et al. COVID-19: Poor outcomes in patients with zinc ' 'deficiency. Int J Infect Dis. 2020;100:343–9.', 'journal-title': 'Int J Infect Dis'}, { 'key': '1095_CR32', 'doi-asserted-by': 'publisher', 'first-page': '108409', 'DOI': '10.1016/j.clim.2020.108409', 'volume': '215', 'author': 'A Gasmi', 'year': '2020', 'unstructured': 'Gasmi A, Noor S, Tippairote T, Dadar M, Menzel A, Bjørklund G. ' 'Individual risk management strategy and potential therapeutic options ' 'for the COVID-19 pandemic. Clin Immunol. 2020;215:108409.', 'journal-title': 'Clin Immunol'}, { 'key': '1095_CR33', 'doi-asserted-by': 'publisher', 'first-page': '1359', 'DOI': '10.3390/nu12051359', 'volume': '12', 'author': 'A D’Avolio', 'year': '2020', 'unstructured': 'D’Avolio A, Avataneo V, Manca A, Cusato J, De Nicolò A, Lucchini R, et ' 'al. 25-hydroxyvitmain D concentrations are lower in patients with ' 'positive PCR for SARS-CoV-2. Nutrients. 2020;12:1359.', 'journal-title': 'Nutrients'}, { 'key': '1095_CR34', 'doi-asserted-by': 'publisher', 'first-page': '688', 'DOI': '10.1016/j.nutres.2014.07.012', 'volume': '34', 'author': 'N Buyukuslu', 'year': '2014', 'unstructured': 'Buyukuslu N, Esin K, Hizli H, Sunal N, Yigit P, Garipagaoglu M. Clothing ' 'preference affects vitamin D status of young women. Nutr Res. ' '2014;34:688–93.', 'journal-title': 'Nutr Res'}, { 'key': '1095_CR35', 'doi-asserted-by': 'crossref', 'unstructured': 'Grant WB, Lordan R. Vitamin D for COVID-19 on trial: An update on ' 'prevention and therapeutic application. Endocr Pract. 2021;27:1266–8.', 'DOI': '10.1016/j.eprac.2021.10.001'}, { 'key': '1095_CR36', 'doi-asserted-by': 'crossref', 'unstructured': 'Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of ' 'vitamin D status and other clinical characteristics with COVID-19 test ' 'results. JAMA. 2020;3:e2019722.', 'DOI': '10.1001/jamanetworkopen.2020.19722'}, { 'key': '1095_CR37', 'first-page': '295', 'volume': '7', 'author': 'ACR Souza', 'year': '2020', 'unstructured': 'Souza ACR, Vasconcelos AR, Prado PS, Pereira CPM. Zinc, Vitamin D and ' 'Vitamin C: perspectives for COVID-19 with a focus on physical tissue ' 'barrier integrity. Front Nutr. 2020;7:295.', 'journal-title': 'Front Nutr'}, { 'key': '1095_CR38', 'doi-asserted-by': 'crossref', 'unstructured': 'Maghbooli Z, Sahraian MA, Jamali-Moghadam SR, Asadi A, Zendehdel A, ' 'Varzandi T, et al. Treatment with 25-hydroxyvitamin D3 (calcifediol) is ' 'associated with a reduction in the blood neutrophil-to-lymphocyte ratio ' 'marker of disease severity in patients hospitalized with COVID-19: a ' 'pilot, multicenter, randomized, placebo-controlled double blind clinical ' 'trial. Endocr Pract. 2021;27:1242–51.', 'DOI': '10.1016/j.eprac.2021.09.016'}, { 'key': '1095_CR39', 'doi-asserted-by': 'publisher', 'first-page': '10', 'DOI': '10.1016/j.nfs.2020.06.001', 'volume': '20', 'author': 'HK Biesalski', 'year': '2020', 'unstructured': 'Biesalski HK. Vitamin D deficiency and co-morbidities in COVID-19 ' 'patients–A fatal relationship? NFS J. 2020;20:10.', 'journal-title': 'NFS J'}, { 'key': '1095_CR40', 'doi-asserted-by': 'publisher', 'first-page': '219', 'DOI': '10.3390/nu13010219', 'volume': '13', 'author': 'S Giannini', 'year': '2021', 'unstructured': 'Giannini S, Passeri G, Tripepi G, Sella S, Fusaro M, Arcidiacono G, et ' 'al. Effectiveness of in-hospital cholecalciferol use on clinical ' 'outcomes in comorbid COVID-19 patients: a hypothesis-generating study. ' 'Nutrients. 2021;13:219.', 'journal-title': 'Nutrients'}, { 'key': '1095_CR41', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1186/s41182-020-00277-w', 'volume': '48', 'author': 'RT Pinzon', 'year': '2020', 'unstructured': 'Pinzon RT, Pradana AW. Vitamin D deficiency among patients with ' 'COVID-19: case series and recent literature review. Trop Med Health. ' '2020;48:1–7.', 'journal-title': 'Trop Med Health'}, { 'key': '1095_CR42', 'doi-asserted-by': 'publisher', 'first-page': '108', 'DOI': '10.1016/j.chest.2020.06.082', 'volume': '159', 'author': 'JS Yao', 'year': '2021', 'unstructured': 'Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, et al. The ' 'minimal effect of zinc on the survival of hospitalized patients with ' 'COVID-19: an observational study. Chest. 2021;159:108–11.', 'journal-title': 'Chest'}, { 'key': '1095_CR43', 'doi-asserted-by': 'crossref', 'unstructured': 'Khalighi A, Jahangirimehr A, Labibzadeh M, Bahmanyari N, Najafi M Serum ' 'Vitamin D, Calcium, and Zinc Levels in Patients with COVID-19. Clin Nutr ' 'ESPEN. 2021;43:276.', 'DOI': '10.1016/j.clnesp.2021.03.040'}, { 'key': '1095_CR44', 'doi-asserted-by': 'publisher', 'first-page': '1228', 'DOI': '10.1099/jmm.0.001250', 'volume': '69', 'author': 'PM Carlucci', 'year': '2020', 'unstructured': 'Carlucci PM, Ahuja T, Petrilli C, Rajagopalan H, Jones S, Rahimian J. ' 'Zinc sulfate in combination with a zinc ionophore may improve outcomes ' 'in hospitalized COVID-19 patients. J Med Microbiol. 2020;69:1228.', 'journal-title': 'J Med Microbiol'}, { 'key': '1095_CR45', 'doi-asserted-by': 'crossref', 'unstructured': 'Thomas S, Patel D, Bittel B, Wolski K, Wang Q, Kumar A, et al. Effect of ' 'high-dose zinc and ascorbic acid supplementation vs usual care on ' 'symptom length and reduction among ambulatory patients with SARS-CoV-2 ' 'infection: the COVID A to Z randomized clinical trial. JAMA Netw Open. ' '2021;4:e210369.', 'DOI': '10.1001/jamanetworkopen.2021.0369'}, { 'key': '1095_CR46', 'doi-asserted-by': 'publisher', 'first-page': 'e00122', 'DOI': '10.1128/mSystems.00122-21', 'volume': '6', 'author': 'R Lordan', 'year': '2021', 'unstructured': 'Lordan R, Rando HM, Greene CS. Dietary supplements and nutraceuticals ' 'under investigation for COVID-19 prevention and treatment. Msystems. ' '2021;6:e00122–21.', 'journal-title': 'Msystems'}, { 'key': '1095_CR47', 'doi-asserted-by': 'publisher', 'first-page': '10349', 'DOI': '10.1021/bi0504761', 'volume': '44', 'author': 'Y-S Han', 'year': '2005', 'unstructured': 'Han Y-S, Chang G-G, Juo C-G, Lee H-J, Yeh S-H, Hsu JT-A, et al. ' 'Papain-like protease 2 (PLP2) from severe acute respiratory syndrome ' 'coronavirus (SARS-CoV): expression, purification, characterization, and ' 'inhibition. Biochem. 2005;44:10349–59.', 'journal-title': 'Biochem'}, { 'key': '1095_CR48', 'doi-asserted-by': 'publisher', 'first-page': '51', 'DOI': '10.1007/s12011-020-02060-8', 'volume': '198', 'author': 'MJ Rios-Lugo', 'year': '2020', 'unstructured': 'Rios-Lugo MJ, Madrigal-Arellano C, Gaytán-Hernández D, Hernández-Mendoza ' 'H, Romero-Guzmán ET. Association of serum zinc levels in overweight and ' 'obesity. Biol Trace Elem Res. 2020;198:51–7.', 'journal-title': 'Biol Trace Elem Res'}, { 'key': '1095_CR49', 'first-page': 'e5721', 'volume': '11', 'author': 'C Orces', 'year': '2019', 'unstructured': 'Orces C. The association between body mass index and vitamin D ' 'supplement use among adults in the United States. Cureus. 2019;11:e5721.', 'journal-title': 'Cureus'}], 'container-title': ['European Journal of Clinical Nutrition'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41430-022-01095-5.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41430-022-01095-5', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41430-022-01095-5.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 23]], 'date-time': '2022-03-23T15:07:04Z', 'timestamp': 1648048024000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41430-022-01095-5'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3, 23]]}, 'references-count': 49, 'alternative-id': ['1095'], 'URL': 'http://dx.doi.org/10.1038/s41430-022-01095-5', 'relation': {}, 'ISSN': ['0954-3007', '1476-5640'], 'issn-type': [{'value': '0954-3007', 'type': 'print'}, {'value': '1476-5640', 'type': 'electronic'}], 'subject': ['Nutrition and Dietetics', 'Medicine (miscellaneous)'], 'published': {'date-parts': [[2022, 3, 23]]}, 'assertion': [ { 'value': '7 October 2021', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '21 January 2022', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '3 February 2022', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '23 March 2022', 'order': 4, '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'}}, { 'value': 'The study protocol was approved by our institute’s Ethics Committee in ' 'Biomedical Research with reference code IR.SBMU.SRC.REC.1399.007.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethical approval'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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