Corresponding author: Ola Alsegai ( osegai@health.gov.bh ) Academic editor: Georgi Momekov
© 2021 Ola Alsegai, Kannan Sridharan, Mona Hammad, Mustafa Mohamed Hammad.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Alsegai O, Sridharan K, Hammad M, Hammad MM (2021) Evaluation of serum vitamin D levels in COVID-19 positive critically ill adults. Pharmacia 68(2): 347-351. https://doi.org/10.3897/pharmacia.68.e64167
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Background: Contradictory evidence exists regarding the association between serum vitamin D levels and the severity and outcomes in coronavirus 2019 (COVID-19) infected patients. We undertook the present study to evaluate the serum vitamin D levels with the other laboratory biomarkers, and the outcomes in our critically ill patients.
Methods: A retrospective observational study was carried out in 58 critically ill adults. Details on their demographics, laboratory parameters such as 25-hydroxy vitamin D [25(OH)D] levels, interleukin-6, serum ferritin, lactate dehydrogenase, creatine kinase (CK), D-dimer, C-reactive protein, fibrinogen, procalcitonin, and erythrocyte sedimentation rate were retrieved. Serum 25(OH)D levels were categorized as follows: ≥50 nmol/L – normal; 30–49 – insufficient; and <30 nmol/L – deficient. Post-hoc, we also compared the outcomes between those with 25(OH)D levels of 80 nmol/L and above, with those of <80 nmol/L.
Results: Fifty-eight patients were recruited of which 31 (53.4%) died. Mean ± SD serum 25(OH)D levels amongst the study participants were 48.5 ± 27.7 nmol/L. Twenty-two (37.9%) individuals had insufficient 25(OH)D levels, and 15 (25.9%) were deficient. Eight (13.8%) participants had their serum 25(OH)D levels ≥80 nmol/L. Median (range) 25(OH)D levels were not significantly different between those who died compared to those alive [41 (20–162) vs. 41 (17–86) nmol/L; p = 0.8]. Significantly higher D-dimer levels were observed amongst those with <80 nmol/L serum 25(OH)D levels. No significant differences were observed between 25(OH)D and other laboratory biomarkers except for elevated CK in patients with insufficient 25(OH)D levels.
Conclusion: We did not observe any significant differences in the serum 25(OH)D levels amongst our critically ill adults who died and who were alive at the time of their admission.
Vitamin D, IL-6, COVID-19, Coronavirus
Coronavirus 2019 (COVID-19) resulted in an unprecedented pandemic affecting 96,218,601 patients with a mortality rate of 2,058,534 at the time of writing this manuscript (COVID-19 dashboard 2021).Vitamin D levels influence the renin-angiotensin system, modulate the cellular and adaptive immunity, and alter the physical barriers to infections, thus playing a vital role in COVID-19 infections (
Ethnicity, cultural practices, latitude, and ultraviolet exposures are some of the core factors influencing vitamin D levels resulting in huge variations between the countries/continents. Considering the dearth of data from the region, we undertook the present study to evaluate serum vitamin D levels in our critically ill patients with COVID-19 infections.
The study was carried out between November 2020 and January 2021 in the Tanta hospital, Egypt. It was a retrospective study amongst critically ill adults with COVID-19 infections whose 25(OH)D level was assessed at the time of admission. The following details were collected: age, gender, laboratory parameters [25(OH)D levels, interleukin-6 (IL-6), serum ferritin, lactate dehydrogenase (LDH), creatine kinase (CK), d-dimer (DD), C-reactive protein (CRP), fibrinogen, procalcitonin, and erythrocyte sedimentation rate (ESR)] and outcome (alive/died). Serum 25(OH)D levels were categorized as follows: ≥50 nmol/L – normal; 30–49– insufficient; and <30 nmol/L – deficient (
Serum 25(OH)D levels were estimated on Siemen’s Advia Centaur using the principles of antibody competitive immunoassay that uses an anti-fluorescein monoclonal mouse antibody covalently bound to paramagnetic particles (PMP), an anti- 25(OH)vitamin D monoclonal mouse antibody labeled with acridinium ester (AE), and a vitamin D analog labeled with fluorescein. The assay range used was 10.5–375 nmol/L.
Descriptive statistics were used for representing the demographic characteristics. Numerical variables were evaluated using either Mann-Whitney U or Kruskal-Wallis H tests. Spearman test was used for assessing the correlations of biomarkers with vitamin D levels. Chi-square tests of association were used for evaluating the categorical variables. A p-value of ≤0.05 was considered significant. SPSS (IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.) was used for statistical analysis.
Fifty-eight patients were recruited with a mean ± SD age of 60.7 ± 14.3 years. Male: female ratio was 27: 31. The mean ± SD hospital length of stay of the study participants was 27.1 ± 6.3 days. Thirty-one (53.4%) died.
Mean ± SD serum 25(OH)D levels amongst the study participants were 48.5 ± 27.7 nmol/L. Twenty-two (37.9%) individuals had insufficient 25(OH)D levels, and 15 (25.9%) were deficient. Median (range) 25(OH)D levels were not significantly different between those who died compared to those alive [41 (20–162) vs. 41 (17–86) nmol/L; p=0.8].Only eight (13.8%) participants had their serum 25(OH)D levels ≥ 80 nmol/L.
No significant differences were observed in the other biomarker levels between those with normal and deficient 25(OH)D (Table
Comparison of the characteristics between individuals with normal, insufficient, and deficient serum 25(OH)D levels.
Parameters | Normal vitamin D levels (n=21) | Insufficient vitamin D levels (n=22) | Deficient vitamin D levels (n=15) | p-values | Participants with serum 25(OH)D levels < 80 nmol/L (n=50) | Participants with serum 25(OH)D levels ≥ 80 nmol/L (n=8) | p-values |
---|---|---|---|---|---|---|---|
Serum IL-6 (pg/ml) | 43 (5–195) | 46 (0.7–5000) | 54 (14.8–609) | 0.9 | 47.6 (0.7–5000) | 47.7 (5–158) | 0.7 |
Serum ferritin (µg/L) | 947.5 (85–2054) | 565 (158–3388) | 384 (33–6681) | 0.4 | 608 (33–6681) | 397 (85–1168) | 0.2 |
Serum LDH (U/L) | 329 (144–916) | 326 (175–850) | 313 (173–700) | 0.8 | 320.5 (173–916) | 343 (144–535) | 0.9 |
Serum creatine kinase (U/L) | 142 (22–573) | 308 (16–1653) | 140 (36–432) | 0.1 | 187 (16–1653) | 131.5 (34–315) | 0.5 |
Serum D-dimer (mg/L) | 1.1 (0.3–8.2) | 0.8 (0.2–80) | 2.3 (0.3–19.7) | 0.2 | 1.2 (0.2–80) | 0.6 (0.3–1.1) | 0.009* |
C-reactive protein (mg/L) | 63.4 (14–192) | 53 (6.8–366) | 94 (14.6–293) | 0.5 | 81.9 (6.8–366) | 59.5 (53–181) | 0.7 |
Serum fibrinogen (mg/dl) | 385 (303–660) | 419 (177–678) | 530 (178–761) | 0.2 | 451 (177–761) | 384 (304–538) | 0.3 |
Procalcitonin (µg/L) | 0.3 (0.04–1.8) | 0.4 (0.1–12) | 0.27 (0.01–3.2) | 0.2 | 0.3 (0.01–12) | 0.4 (0.04–0.5) | 0.9 |
ESR (mm/hour) | 74 (30–123) | 32 (20–115) | 66 (5–107) | 0.3 | 63 (5–123) | 44.5 (44–45) | 0.6 |
We carried out the present study in 58 critically ill patients with 25(OH)D levels assayed on admission. We did not observe any significant differences in the serum levels of 25(OH)D between those who died and those who are alive. No significant differences were observed with other laboratory biomarkers except for elevated creatine kinase levels in individuals with insufficient 25(OH)D levels and elevated DD levels amongst those with serum 25(OH)D < 80 nmol/L.
Jain et al. in 2020 reported in 154 COVID-19 positive patients of which 63 had severe illness requiring admission in the critical care unit, and 91 were asymptomatic revealed a prevalence of vitamin D deficiency to an extent of 96.82 and 32.96%, respectively. Additionally, the authors observed significantly elevated inflammatory markers such as IL-6, serum ferritin, and tumor necrosis factor-alpha with an increased mortality risk amongst those with hypovitaminosis D. However, we did not observe any such differences that can be possibly explained by the following reasons: measurement of 25(OH)D levels were carried out at the time of admission while it may have reduced when the patient deteriorated; and that the present study was carried out during November until January during which the prevalence of vitamin D deficiency in general, is lower in our region. Studies have explored the potential influence of the latitudinal position of countries on the severity and mortality of COVID-19 infections, but nothing was inconclusive (
We did not observe any significant differences in the serum 25(OH)D levels in our critically ill patients who died and who were alive at the time of their admission.