Correlation of Plasma 25(OH)D3 and Vitamin D Binding Protein Levels with COVID-19 Severity and Outcome in Hospitalized Patients

Abstract

Background: The Coronavirus Disease-19 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a worldwide pandemic. The severity of COVID-19 varies greatly across infected individuals. Possible factors may include plasma levels of 25(OH)D and vitamin D binding protein (DBP), as both are involved in the host immune response. Other possible nutrition-related factors include malnutrition and/or obesity which disrupt the optimal host immune response to infections. Current literature shows inconsistent evidence about the association of plasma 25(OH)D3 and DBP on infection severity and clinical outcomes. Objectives: This study aimed to measure plasma 25(OH)D3 and DBP in hospitalized COVID-19 cases and assess their correlation with infection severity, inflammatory markers, and clinical outcome. Methods: 167 patients were included in this analytical cross-sectional study, of which 81 were critical and 86 were non-critical hospitalized COVID-19 patients. Plasma levels of 25(OH)D3, DBP, and the inflammatory cytokines, IL-6, IL-8, IL-10, and TNF-α were assessed using the Enzyme-linked Immunosorbent Assay (ELISA). Information regarding biochemical and anthropometrical indices, hospital length of stay (LoS), and illness outcome was obtained from the medical records. Results: Plasma 25(OH)D3 level was found to be significantly lower in critical compared to non-critical patients (Median = 8.38 (IQR = 2.33) vs. 9.83 (IQR = 3.03) nmol/L, respectively; p < 0.001), and it positively correlated with hospital LoS. However, plasma 25(OH)D3 did not correlate with mortality or any of the inflammatory markers. DBP on the other hand correlated positively with mortality (rs = 0.188, p = 0.015) and hospital LoS (rs = 0.233, p = 0.002). DBP was significantly higher in critical than non-critical patients (Median = 1262.18 (IQR = 463.66) vs. 1153.35 (IQR = 418.46) ng/mL, respectively; p < 0.001). Furthermore, IL-6 and IL-8 were significantly higher in critical than non-critical patients. However, no differences were found in IL-10, TNF-α, IL-10/TNF-α, TNF-α/IL-10, IL-6/IL-10, or CRP between groups. Conclusion: The current study found that critical COVID-19 patients had lower 25(OH)D3 than non-critical patients, yet, levels were found to be suboptimal in both groups. Further, critical patients had higher DBP levels as compared to non-critical patients. This finding may encourage future research to unravel the effects of this understudied protein that appears to have significant associations with inflammation, even though the precise mechanism is unknown.

The Expression of VDBP in the Severe COVID-19 and its Role in Acute Lung Injury

“…Multiple studies have con rmed a signi cant correlation between VDBP gene polymorphism and COVID-19 [7][8][9][10][11][12], but there is no consistent conclusion between VDBP and the severity and mortality of COVID-19. Alabdullatif W. found that the VDBP of the critical COVID-19 was signi cantly higher than that of the non-critical group [13], which is consistent with our ndings. Povaliaeva A. also found that VDBP in COVID-19 patients was higher than in healthy people, but the correlation between VDBP and the severity was insigni cant [14].…”

“…Vitamin D-binding protein (VDBP), which was well known as the primary carrier of vitamin D metabolites, was also found to be closely related to COVID-19 in recent research [7][8][9][10][11][12][13][14][15][16]. Previous studies discovered that VDBP not only plays a vital role in maintaining stable serum level of vitamin D and modulating its bioavailability but also play an essential role in the progress of in ammatory and immunoregulation functions independent of vitamin D carriage [17].…”