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

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.