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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\u00b1\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\u00b1\u200911.4\u2009ng\/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3\u2009\u00b1\u20098.5\u2009ng\/mL and 25.4\u2009\u00b1\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\u00b1\u20098.6\u2009ng\/mL and 43.0 (19.0\u201356.0) pg\/mL, respectively], than in those not requiring ICU admission [22.4\u2009\u00b1\u20091.4\u2009ng\/mL,<jats:italic>p<\/jats:italic>\u2009=\u20090.0001 and 16.0 (8.0\u201332.0) 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\u00b1\u20096.4\u2009ng\/mL and 45.0 (28.0\u201399.0) pg\/mL] with survivors [19.3\u2009\u00b1\u200912.0\u2009ng\/mL,<jats:italic>p<\/jats:italic>\u2009=\u20090.035 and 21.0 (10.5\u201345.9) pg\/mL,<jats:italic>p<\/jats:italic>\u2009=\u20090.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (\u03c1 \u2212\u20090.284,<jats:italic>p<\/jats:italic>\u2009=\u20090.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98\u20131.00,<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\u20130.99, 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":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"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":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Gennari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Merlotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mingiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Frosali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Giovanelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Torlasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino F.","family":"Pengo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Heilbron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Soranna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Zambon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Aresta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bonomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Cangiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Favero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Fatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Battista","family":"Perego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-3300","authenticated-orcid":false,"given":"Iacopo","family":"Chiodini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Parati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Persani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"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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