Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity

Abstract

IntroductionCoronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined.MethodsConsecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20 ng/ml (<50nmol/L) and deficient Vitamin D as a level ≤12 ng/ml (<30 nmol/L).ResultsOf the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24–3.58, p = 0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat.ConclusionVitamin D deficiency (≤12 ng/ml or <30 nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.

Commentary: Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity

“…The prevalence and mortality owing to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were negatively correlated with the DBP1 allele frequency (a combination of DBP1S and DBP1F). This finding could be partly explained by the potential protective effects of vitamin D, as described in the paper of Vanegas-Cedillo et al ( 1 ). In another study, polymorphisms in the DBP gene were also related to the infection severity of COVID-19 ( 7 ).…”

“…Because only around 4% of DBP is conjugated with vitamin D metabolites, this plasma protein performs a variety of additional tasks, including actin scavenging, fatty acid-binding, endotoxin transporting, and chemotactic cofactor activating ( 8 ). Low vitamin D concentrations may contribute to a pro-thrombotic and pro-inflammatory state, which is observed in COVID-19 patients ( 1 ). In both pathophysiological pathways, DBP might play a key role.…”

“…With interest, we read the paper of Vanegas-Cedillo et al ( 1 ), which showed an independent association between vitamin D deficiency and COVID-19 mortality, after adjustment for BMI and epicardial fat. Vitamin D deficiency may contribute to a pro-thrombotic and pro-inflammatory state in COVID-19.…”

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19

“…Vitamin D sufficiency improves immune functions [ 54 ]. It significantly reduces the risk of viral and bacterial respiratory infections [ 55 , 56 , 57 ] and lowers the risk of adverse outcomes from COVID-19: including mortality from SARS-CoV-2 [ 55 ] and complications following immunisation. As illustrated in Figure 3 , the death rate from COVID-19 is four-fold less, having a serum 25(OH)D concentration above 50 ng/mL [ 55 ].…”

“…It significantly reduces the risk of viral and bacterial respiratory infections [ 55 , 56 , 57 ] and lowers the risk of adverse outcomes from COVID-19: including mortality from SARS-CoV-2 [ 55 ] and complications following immunisation. As illustrated in Figure 3 , the death rate from COVID-19 is four-fold less, having a serum 25(OH)D concentration above 50 ng/mL [ 55 ]. A single bolus dose of vitamin D or calcifediol discussed above or an upfront loading dose of vitamin D discussed later can rapidly reach the mentioned therapeutic serum 25(OH)D concentration and, thus, improve clinical outcomes.…”