Abstract: Campi et al. BMC Infectious Diseases (2021) 21:566 https://doi.org/10.1186/s12879-021-06281-7 RESEARCH ARTICLE Open Access Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy Irene Campi1,2†, Luigi Gennari3†, Daniela Merlotti3, Christian Mingiano3, Alessandro Frosali3, Luca Giovanelli1,4, Camilla Torlasco5,6, Martino F. Pengo5,6, Francesca Heilbron5,6, Davide Soranna7, Antonella Zambon7,8, Marta Di Stefano1,4, Carmen Aresta1,4, Marco Bonomi1,4, Biagio Cangiano1,4, Vittoria Favero1,4, Letizia Fatti1,4, Giovanni Battista Perego5, Iacopo Chiodini1,4* , Gianfranco Parati5,6† and Luca Persani1,4† Abstract Background: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-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) IL6 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. * Correspondence: iacopo.chiodini@unimi.it; i.chiodini@auxologico.it † Irene Campi and Luigi Gennari equally contributed to the study. Gianfranco Parati and Luca Persani are co-senior authors. 1 Department of Endocrine and Metabolic Diseases & Lab of Endocrine and Metabolic Research, IRCCS, Istituto Auxologico Italiano, Via Magnasco 2, 20149 Milan, Italy 4 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and..