25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients
Nguyen N Nguyen, Muppala N P Raju, Briget Da Graca, Dapeng Wang, Nada A Mohamed, Manohar B Mutnal, Arundhati Rao, Monica Bennett, Matthew Gokingco, Huy Pham, Amin A Mohammad
PLOS ONE, doi:10.1371/journal.pone.0268038
Objectives Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes. Methods We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher's exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used.
Results COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/ mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53-18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95%
Supporting information
S1 Table. Full models for adjusted evaluation of mortality, need for ventilation, and LOS. Full models for adjusted evaluation of mortality, need for ventilation, and LOS for COVID-19 positive patients at deficiency and insufficiency cutoffs for 25-OH-D3 and tD. Logistic regression was used for mortality and ventilation, and Cox proportional hazards was used for LOS.
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DOI record:
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"abstract": "<jats:sec id=\"sec001\">\n<jats:title>Objectives</jats:title>\n<jats:p>Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher’s exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53–18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95% CI]: 2.75 [1.10–6.90]).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions</jats:title>\n<jats:p>There is an inverse relationship of 25-hydroxyvitamin D levels and hospital LOS for COVID-19 patients. Vitamin D status is a predictor for severity of outcomes. LCMS results are useful for assessing the odds of mortality and the need for ventilation during hospitalization.</jats:p>\n</jats:sec>",
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