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Vitamin D and COVID-19 Severity and Related Mortality: A Prospective Study in Italy

25 Pages Posted: 27 Oct 2020

See all articles by Irene Campi

Irene Campi

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Luigi Gennari

University of Siena - Department of Medical, Surgical and Neurological Sciences

Daniela Merlotti

University of Siena - Department of Medical, Surgical and Neurological Sciences

Christian Mingiano

University of Siena - Department of Medical, Surgical and Neurological Sciences

Alessandro Frosali

University of Siena - Department of Medical, Surgical and Neurological Sciences

Luca Giovanelli

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Camilla Torlasco

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences

Martino F. Pengo

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences

Francesca Heilbron

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences

Davide Soranna

IRCCS Istituto Auxologico Italiano - Department of Medicine and Surgery

Antonella Zambon

IRCCS Istituto Auxologico Italiano - Department of Medicine and Surgery

Marta Di Stefano

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Carmen Aresta

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Marco Bonomi

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Biagio Cangiano

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Vittoria Favero

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Letizia Fatti

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Giovanni Battista Perego

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences

Iacopo Chiodini

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Gianfranco Parati

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Luca Persani

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

More...

Abstract

Background: The possibility that vitamin D deficiency might favor a poorer outcome of Coronavirus disease-19 (COVID-19) is debated. We aimed to assess the association between 25-hydroxyvitamin-D (25OHD) levels and COVID-19 severity and mortality.  

Methods: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1±14.1 years, 70 males) for moderately-to-severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 matched subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization.

Findings: Moderately-to-severely-symptomatic COVID-19 patients had lower 25OHD levels (45.5±28.5 nmol/L) than mildly-symptomatic COVID-19 patients and non SARS-CoV-2 infected controls (75.8±21.3 nmol/L and 63.5±23.5 nmol/L, respectively, p<0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in moderately-to-severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 36.0±21.5 nmol/L and 43.0 [19.0-56.0] pg/mL, respectively], than in those not requiring ICU admission (56.0±31.8 nmol/L, 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 (33.0±16.0 ng/mL and 45.0 [28.0-99.0] pg/mL) with survivors (48.3±30 nmol/L, p=0.035 and 21.0 [10.5-45.9] pg/mL, p=0.018, respectively). 25OHD levels inversely correlated with IL-6 levels (ρ -0.284, p=0.004) and with the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p=0.011] and mortality (RR 0.97, 95%CI, 0.95-0.99, p=0.011) regardless of confounding factors.

Interpretation: Vitamin D levels were positively correlated with higher IL-6 levels and negatively associated to COVID-19 severity and mortality.

Funding: None.

Declaration of Interests: All authors declare no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.

Ethics Approval Statement: 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.

Keywords: vitamin D, COVID-19, mortality, interleukin-6

Suggested Citation

Campi, Irene and Gennari, Luigi and Merlotti, Daniela and Mingiano, Christian and Frosali, Alessandro and Giovanelli, Luca and Torlasco, Camilla and Pengo, Martino F. and Heilbron, Francesca and Soranna, Davide and Zambon, Antonella and Di Stefano, Marta and Aresta, Carmen and Bonomi, Marco and Cangiano, Biagio and Favero, Vittoria and Fatti, Letizia and Perego, Giovanni Battista and Chiodini, Iacopo and Parati, Gianfranco and Persani, Luca, Vitamin D and COVID-19 Severity and Related Mortality: A Prospective Study in Italy. Available at SSRN: https://ssrn.com/abstract=3697179 or http://dx.doi.org/10.2139/ssrn.3697179

Irene Campi

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Via Festa del Perdono, 7
Milan, 20122
Italy

Luigi Gennari

University of Siena - Department of Medical, Surgical and Neurological Sciences ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Daniela Merlotti

University of Siena - Department of Medical, Surgical and Neurological Sciences ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Christian Mingiano

University of Siena - Department of Medical, Surgical and Neurological Sciences ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Alessandro Frosali

University of Siena - Department of Medical, Surgical and Neurological Sciences ( email )

Via Banchi di Sotto, 55
Siena, 53100
Italy

Luca Giovanelli

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Camilla Torlasco

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Martino F. Pengo

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Francesca Heilbron

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Davide Soranna

IRCCS Istituto Auxologico Italiano - Department of Medicine and Surgery ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Antonella Zambon

IRCCS Istituto Auxologico Italiano - Department of Medicine and Surgery ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Marta Di Stefano

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Carmen Aresta

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Marco Bonomi

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Biagio Cangiano

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Vittoria Favero

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Via Festa del Perdono, 7
Milan, 20122
Italy

Letizia Fatti

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Giovanni Battista Perego

IRCCS Istituto Auxologico Italiano - Department of Cardiovascular, Neural and Metabolic Sciences ( email )

Via Pellizza da Volpedo, 41
Milano, 20149
Italy

Iacopo Chiodini (Contact Author)

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Gianfranco Parati

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases ( email )

Italy

Luca Persani

IRCCS Istituto Auxologico Italiano - Department of Endocrine and Metabolic Diseases

Via Festa del Perdono, 7
Milan, 20122
Italy

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