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All Studies   Meta Analysis    Recent:   

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy

Campi et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06281-7
Jun 2021  
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Severe case 88% treatment Improvement Relative Risk Death for severe patients 24% levels ICU for severe patients 53% levels Vitamin D for COVID-19  Campi et al.  Prophylaxis Is prophylaxis with vitamin D beneficial for COVID-19? Prospective study of 155 patients in Italy Lower severe cases with vitamin D (p<0.000001) c19early.org Campi et al., BMC Infectious Diseases, Jun 2021 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
Prospective study of 103 hospitalized patients in Italy, showing very high prevalence of vitamin D deficiency, and increased severity for lower vitamin D levels. Vitamin D supplementation was significantly less common for cases.
This is the 40th 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.
risk of severe case, 88.4% lower, OR 0.12, p < 0.001, treatment 31 of 103 (30.1%) cases, 41 of 52 (78.8%) controls, NNT 2.3, case control OR, vitamin D supplementation, hospitalized patients vs. controls, excluded in exclusion analyses: significant unadjusted differences between groups.
risk of death for severe patients, 24.3% lower, RR 0.76, p = 0.53, high D levels (≥20ng/ml) 6 of 39 (15.4%), low D levels (<20ng/ml) 13 of 64 (20.3%), NNT 20, hospitalized patients, outcome based on serum levels.
risk of ICU for severe patients, 53.1% lower, RR 0.47, p < 0.001, high D levels (≥20ng/ml) 12 of 39 (30.8%), low D levels (<20ng/ml) 42 of 64 (65.6%), NNT 2.9, hospitalized patients, outcome based on serum levels.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Campi et al., 14 Jun 2021, prospective, Italy, peer-reviewed, 21 authors, dosage not specified.
This PaperVitamin DAll
Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy
Irene Campi, Luigi Gennari, Daniela Merlotti, Christian Mingiano, Alessandro Frosali, Luca Giovanelli, Camilla Torlasco, Martino F Pengo, Francesca Heilbron, Davide Soranna, Antonella Zambon, Marta Di Stefano, Carmen Aresta, Marco Bonomi, Biagio Cangiano, Vittoria Favero, Letizia Fatti, Giovanni Battista Perego, Iacopo Chiodini, Gianfranco Parati, Luca Persani
BMC Infectious Diseases, doi:10.1186/s12879-021-06281-7
Background: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 . We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. Methods: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. Results: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ − 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count.
Authors' contributions IC1: data collection, analysis and interpretation of the data, preparation of the manuscript. LG1: data collection, analysis and interpretation of the data, preparation of the manuscript. DM: data collection and analysis, preparation of the manuscript. CM data collection and analysis. AF: data collection and analysis. LG2: data collection and analysis. CT: data collection and analysis. MFP: data collection and analysis. FH data collection and analysis. D S: data analysis and statistics. AZ: data analysis and statistics. MD: data collection and analysis. CA: data collection and analysis. MB: data collection and analysis and revision of the manuscript. BC: data collection and analysis. VF: data collection and analysis. LF: data collection and analysis. GBP: data collection and analysis and revision of the manuscript. IC2: data collection, analysis and interpretation of the data, preparation of the manuscript. GP: data collection, analysis and interpretation of the data, preparation of the manuscript. LP: data analysis and interpretation, preparation of the manuscript. All authors have read and approved the final version of the manuscript. Declarations Ethics approval and consent to participate The study was approved by the ethics committee of our Institution (Ethical Committee, Istituto Auxologico Italiano). The participants or their familiar, when needed as in the case of ICU admitted patients, gave written informed consent before taking part in the..
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We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with ' 'interleukin 6 (IL-6) levels and with disease severity and mortality in ' 'COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We ' 'prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1\u2009' '±\u200914.1\u2009years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with ' 'SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and ' '206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at ' 'admission and focused on respiratory outcome during ' 'hospitalization.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Severely-symptomatic ' 'COVID-19 patients had lower 25OHD levels (18.2\u2009±\u200911.4\u2009ng/mL) than ' 'mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3\u2009±\u2009' '8.5\u2009ng/mL and 25.4\u2009±\u20099.4\u2009ng/mL, ' 'respectively,<jats:italic>p</jats:italic>\u2009&lt;\u20090.0001 for both comparisons). 25OHD ' 'and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients ' 'admitted to intensive care Unit [(ICU), 14.4\u2009±\u20098.6\u2009ng/mL and 43.0 (19.0–56.0) ' 'pg/mL, respectively], than in those not requiring ICU admission [22.4\u2009±\u20091.4\u2009' 'ng/mL,<jats:italic>p</jats:italic>\u2009=\u20090.0001 and 16.0 (8.0–32.0) ' 'pg/mL,<jats:italic>p</jats:italic>\u2009=\u20090.0002, respectively]. Similar differences ' 'were found when comparing COVID-19 patients who died in hospital [13.2\u2009±\u20096.4\u2009' 'ng/mL and 45.0 (28.0–99.0) pg/mL] with survivors [19.3\u2009±\u200912.0\u2009' 'ng/mL,<jats:italic>p</jats:italic>\u2009=\u20090.035 and 21.0 (10.5–45.9) ' 'pg/mL,<jats:italic>p</jats:italic>\u2009=\u20090.018, respectively). 25OHD levels inversely ' 'correlated with: i) IL-6 levels (ρ −\u20090.284,<jats:italic>p</jats:italic>\u2009=\u2009' '0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence ' 'interval (95%CI) 0.98–1.00,<jats:italic>p</jats:italic>\u2009=\u20090.011] regardless of age, ' 'gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, ' 'creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and ' 'platelets count; iii) mortality (RR 0.97, 95%CI, 0.95–0.99, p\u2009=\u20090.011) regardless ' 'of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase ' 'levels, neutrophil cells, lymphocytes and platelets ' 'count.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In our ' 'COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were ' 'independent predictors of COVID-19 severity and mortality.</jats:p></jats:sec>', 'DOI': '10.1186/s12879-021-06281-7', 'type': 'journal-article', 'created': {'date-parts': [[2021, 6, 14]], 'date-time': '2021-06-14T08:16:49Z', 'timestamp': 1623658609000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 79, 'title': 'Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy', 'prefix': '10.1186', 'volume': '21', 'author': [ {'given': 'Irene', 'family': 'Campi', 'sequence': 'first', 'affiliation': []}, {'given': 'Luigi', 'family': 'Gennari', 'sequence': 'additional', 'affiliation': []}, {'given': 'Daniela', 'family': 'Merlotti', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christian', 'family': 'Mingiano', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alessandro', 'family': 'Frosali', 'sequence': 'additional', 'affiliation': []}, {'given': 'Luca', 'family': 'Giovanelli', 'sequence': 'additional', 'affiliation': []}, {'given': 'Camilla', 'family': 'Torlasco', 'sequence': 'additional', 'affiliation': []}, {'given': 'Martino F.', 'family': 'Pengo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Francesca', 'family': 'Heilbron', 'sequence': 'additional', 'affiliation': []}, {'given': 'Davide', 'family': 'Soranna', 'sequence': 'additional', 'affiliation': []}, {'given': 'Antonella', 'family': 'Zambon', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marta', 'family': 'Di Stefano', 'sequence': 'additional', 'affiliation': []}, {'given': 'Carmen', 'family': 'Aresta', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marco', 'family': 'Bonomi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Biagio', 'family': 'Cangiano', 'sequence': 'additional', 'affiliation': []}, {'given': 'Vittoria', 'family': 'Favero', 'sequence': 'additional', 'affiliation': []}, {'given': 'Letizia', 'family': 'Fatti', 'sequence': 'additional', 'affiliation': []}, {'given': 'Giovanni Battista', 'family': 'Perego', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-7594-3300', 'authenticated-orcid': False, 'given': 'Iacopo', 'family': 'Chiodini', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gianfranco', 'family': 'Parati', 'sequence': 'additional', 'affiliation': []}, {'given': 'Luca', 'family': 'Persani', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2021, 6, 14]]}, 'reference': [ { 'issue': '16', 'key': '6281_CR1', 'doi-asserted-by': 'publisher', 'first-page': '1559', 'DOI': '10.1001/jama.2020.5775', 'volume': '323', 'author': 'DJ Cook', 'year': '2020', 'unstructured': 'Cook DJ, Marshall JC, Fowler RA. 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' '2020;287(17):3689–92. https://doi.org/10.1111/febs.15534.', 'journal-title': 'FEBS J'}, { 'key': '6281_CR52', 'doi-asserted-by': 'publisher', 'first-page': '105751', 'DOI': '10.1016/j.jsbmb.2020.105751', 'volume': '203', 'author': 'M Entrenas Castillo', 'year': '2020', 'unstructured': 'Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz ' 'JF, López Miranda J, Bouillon R, et al. Effect of calcifediol treatment ' 'and best available therapy versus best available therapy on intensive ' 'care unit admission and mortality among patients hospitalized for ' 'COVID-19: a pilot randomized clinical study. J Steroid Biochem Mol Biol. ' '2020;203:105751. https://doi.org/10.1016/j.jsbmb.2020.105751.', 'journal-title': 'J Steroid Biochem Mol Biol'}, { 'issue': '24', 'key': '6281_CR53', 'doi-asserted-by': 'publisher', 'first-page': '24522', 'DOI': '10.18632/aging.202307', 'volume': '12', 'author': 'B Cangiano', 'year': '2020', 'unstructured': 'Cangiano B, Fatti LM, Danesi L, Gazzano G, Croci M, Vitale G, et al. ' 'Mortality in an Italian nursing home during COVID-19 pandemic: ' 'correlation with gender, age, ADL, vitamin D supplementation, and ' 'limitations of the diagnostic tests. Aging (Albany NY). ' '2020;12(24):24522–34. https://doi.org/10.18632/aging.202307.', 'journal-title': 'Aging (Albany NY)'}, { 'issue': '11', 'key': '6281_CR54', 'doi-asserted-by': 'publisher', 'first-page': '3377', 'DOI': '10.3390/nu12113377', 'volume': '12', 'author': 'G Annweiler', 'year': '2020', 'unstructured': 'Annweiler G, Corvaisier M, Gautier J, Dubée V, Legrand E, Sacco G, et ' 'al. Vitamin D supplementation associated to better survival in ' 'hospitalized frail elderly COVID-19 patients: the GERIA-COVID ' 'quasi-experimental study. Nutrients. 2020;12(11):3377. ' 'https://doi.org/10.3390/nu12113377.', 'journal-title': 'Nutrients'}, { 'key': '6281_CR55', 'doi-asserted-by': 'crossref', 'unstructured': 'Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et ' 'al. Short term, high-dose vitamin D supplementation for COVID-19 ' 'disease: a randomised, placebo-controlled, study (SHADE study). Postgrad ' 'Med J. 2020;139065.', 'DOI': '10.1136/postgradmedj-2020-139065'}, { 'issue': '11', 'key': '6281_CR56', 'doi-asserted-by': 'publisher', 'first-page': '1053', 'DOI': '10.1001/jama.2020.26848', 'volume': '325', 'author': 'IH Murai', 'year': '2021', 'unstructured': 'Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, et ' 'al. Effect of a single high dose of vitamin D3 on hospital length of ' 'stay in patients with moderate to severe COVID-19: a randomized clinical ' 'trial. JAMA. 2021 Mar 16;325(11):1053–60. ' 'https://doi.org/10.1001/jama.2020.26848.', 'journal-title': 'JAMA.'}], 'container-title': 'BMC Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-021-06281-7.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12879-021-06281-7/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12879-021-06281-7.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 12, 31]], 'date-time': '2022-12-31T00:57:52Z', 'timestamp': 1672448272000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06281-7'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 6, 14]]}, 'references-count': 56, 'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2021, 12]]}}, 'alternative-id': ['6281'], 'URL': 'http://dx.doi.org/10.1186/s12879-021-06281-7', 'relation': {}, 'ISSN': ['1471-2334'], 'subject': ['Infectious Diseases'], 'container-title-short': 'BMC Infect Dis', 'published': {'date-parts': [[2021, 6, 14]]}, 'assertion': [ { 'value': '17 November 2020', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '3 June 2021', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '14 June 2021', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The study was approved by the ethics committee of our Institution (Ethical ' 'Committee, Istituto Auxologico Italiano). The participants or their familiar, ' 'when needed as in the case of ICU admitted patients, gave written informed ' 'consent before taking part in the study.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'All authors declare: no support from any organization for the submitted work; ' 'no financial relationships with any organizations that might have an interest ' 'in this work; no other relationships or activities that could appear to have ' 'influenced this work.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '566'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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