Vitamin D Status as a Potential Modifiable Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Abstract

Abstract In March 2020, the infection COVID-19 spread as a pandemic emergence. Among multiple biological and environmental factors, hypovitaminosis D is a credible candidate. The aim of this study is to shed light on the pathogenic role of vitamin D deficiency in the susceptibility to SARS-CoV-2 and in the aggressive immune and inflammatory response by the host. We retrospectively analyzed the biochemical panel of immune system markers and the tandem mass spectrometry coupled to liquid chromatography (LC-MS-MS) measured vitamin D, in the serum samples of patients with SARS-CoV-2 studied in all aspects of clinical relevant parameters. RESULTS between 18th March and 20th April 2020 we enrolled 29 consecutive patients with COVID-19. They were 17 (58.6%) males and 12 (41.4) females, and the median age was 79 (69–88) years. Mean 25OHD was 17.3±2.1 ng/ml, with a median of 15.7 1 ng/ml (i.r. 6.7–25). Twenty-five patients (86.2%) had 25OHD levels <30 ng/ml, 18 patients (62.0%) had 25OHD levels <20 ng/ml and 10 patients (34.5%) had severe vitamin D deficiency (<10 ng/ml). In the group of patients with severe disease (ARDS, cardiovascular complications, CID) 69.2% (n=9/13) of patients presented hypovitaminosis D (<20 ng/ml). All patients who dead for COVID-19 during hospitalization (n=6) had 25OHD≤30 ng/ml and 5/6 had 25OHD≤20 ng/ml. IL-6 and CRP were measured in all patients and were considered surrogate markers of cytokines storm. The majority of patients had levels of IL-6 (n=22, 75.8%) and CRP (n=25, 86.2%) above the upper limit of the reference range of our laboratory (IL6 6.59 and CRP 1 mg/dl) and the median was IL 6=16.1 (i.r. 7.3–36.3) and CRP=6.67 (2.64–11.52). Patients with 25OHD <20 ng/ml had higher levels of IL-6 (p=0.004; 19.9 vs 10.4) and CRP (p=0.009, 9.85 vs 1.40) and did not differ for the other clinical and biochemical variables. If we considered as 25OHD cut-off the mean value in our population (17.3 ng/ml), patients with lower levels of 25OHD had higher age (p=0.033) and higher levels of IL6 (p=0.016), CRP (p=0.04), troponin (p=0.04) and D-dimer (p=0.017), compared to the others. An inverse correlation was found between 25OHD levels and IL-6, CRP, and troponin. In a univariate regression analysis hypovitaminosis D (<20 ng/ml) was a predictive factor for IL6 (expressed as LnIL6) levels (β=0.57, P=0.003) and for PCR levels (β=0.42, P=0.034). We also performed a multivariate regression analysis with hypovitaminosis D (<20 ng/ml), sex, BMI, age (<70 years) and ARDS as independent variables. Notably, hypovitaminosis D (β=0.49, P<0.02), BMI (β=0.4, P=0.04) and ARDS (β=0.44, P=0.02) were confirmed to be significant variables for IL6 (expressed as LnIL6) level prediction. In the same multivariate model hypovitaminosis D (β=0.49, P=0.034) was confirmed as independent predictor of CRP levels. In conclusion, hypovitaminosis D is related to the negative prognostic inflammatory status in patients with SARS-Cov2.