Vitamin D Status in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients
Wael Hafez, Husam Saleh, Arun Arya, Mouhamad Alzouhbi, Osman Fdl Alla, Kumar Lal, Samy Kishk, Sara Ali, Srinivasa Raghu, Walaa Elgaili, Wissam Abdul Hadi
Frontiers in Medicine, doi:10.3389/fmed.2022.843737
Coronavirus Disease (COVID-19) is a newly emerged infectious disease that first appeared in China. Vitamin D is a steroid hormone with an anti-inflammatory protective role during viral infections, including SARS-CoV-2 infection, via regulating the innate and adaptive immune responses. The study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25[OH]D) levels and clinical outcomes of COVID-19. This was a retrospective study of 126 COVID-19 patients treated in NMC Royal Hospital, UAE. The mean age of patients was 43 ± 12 years. Eighty three percentage of patients were males, 51% patients were with sufficient (> 20 ng/mL), 41% with insufficient (12-20 ng/mL), and 8% with deficient (<12 ng/mL) serum 25(OH)D levels. There was a statistically significant correlation between vitamin D deficiency and mortality (p = 0.04). There was a statistically significant correlation between 25(OH)D levels and ICU admission (p = 0.03), but not with the need for mechanical ventilation (p = 0.07). The results showed increased severity and mortality by 9 and 13%, respectively, for each one-year increase in age. This effect was maintained after adjustment for age and gender (Model-1) and age, gender, race, and co-morbidities (Models-2,3). 25(OH)D levels (<12 ng/mL) showed a significant increase in mortality by eight folds before adjustments (p = 0.01), by 12 folds in Model-1 (p = 0.04), and by 62 folds in the Model-2. 25(OH)D levels (< 20 ng/mL) showed no association with mortality before adjustment and in Model-1. However, it showed a significant increase in mortality by 29 folds in Model-3. Neither 25(OH)D levels (<12 ng/mL) nor (< 20 ng/mL) were risk factors for severity. Radiological findings were not significantly different among patients with different 25(OH)D levels. Despite observed shorter time till viral clearance and time from cytokine release storm to recovery among patients with sufficient 25(OH)D levels, the findings were statistically insignificant. In conclusion, we demonstrated a significant correlation between vitamin D deficiency and poor COVID-19 outcomes.
CONCLUSION In summary, our study showed a statistically significant correlation between deficient serum 25(OH)D levels (<12 ng/mL) and poor clinical outcomes among COVID-19 patients. Given our findings and vitamin D's safety as well as its broad therapeutic window, public health policies may recommend vitamin D supplementation to improve COVID-19 patient outcomes, particularly among individuals at high risk of SARS-CoV-2 infection and patients with risk factors for poor COVID-19 outcomes and initial vitamin d deficiency. Larger controlled trials are recommended to control possible confounding factors and determine the optimal cut-off values of serum vitamin D levels.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by Abu Dhabi Health COVID-19 Research Ethics Committee (DOH/CVDC/2020/231). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
AUTHOR CONTRIBUTIONS WH: literature review, conceptualization, project administration, data analysis and interpretation, revising, writing of original and final draft, and sharing in writing the manuscript. AA, HS, SA, OF, KL, SR, MA, WA, SK, and WE: literature review, analysis, interpretation of data, revising the work, editing, final approval of the version to be published, and agreement to be accountable for all aspects of the work. All authors have contributed to the article, and read and..
References
Aglipay, Birken, Parkin, Loeb, Thorpe et al., Effect of high-dose vs standard-dose wintertime vitamin D supplementation on viral upper respiratory tract infections in young healthy children, JAMA,
doi:10.1001/jama.2017.8708Akbar, Wibowo, Pranata, Setiabudiawan, Low serum 25-hydroxyvitamin D (Vitamin D) level is associated with susceptibility to COVID-19, severity, and mortality: a systematic review and meta-analysis, Front Nutr,
doi:10.3389/fnut.2021.660420Alsafar, Grant, Hijazi, Uddin, Alkaabi et al., COVID-19 disease severity and death in relation to vitamin D status among SARS-CoV-2-positive UAE residents, Nutrients,
doi:10.3390/nu13051714Angelidi, Belanger, Lorinsky, Karamanis, Chamorro-Pareja et al., Vitamin D status is associated with in-hospital mortality and mechanical ventilation: a cohort of COVID-19 hospitalized patients, Mayo Clin Proc,
doi:10.1016/j.mayocp.2021.01.001Arihiro, Nakashima, Matsuoka, Suto, Uchiyama et al., Randomized trial of vitamin D supplementation to prevent seasonal influenza and upper respiratory infection in patients with inflammatory bowel disease, Inflamm Bowel Dis,
doi:10.1093/ibd/izy346Bui, Zhu, Hawkins, Cortez-Resendiz, Bellon, Vitamin D regulation of the immune system and its implications for COVID-19: a mini review, SAGE Open Med,
doi:10.1177/20503121211014073Capuano, Rossi, Paolisso, COVID-19 kills more men than women: an overview of possible reasons, Front Cardiovasc Med,
doi:10.3389/fcvm.2020.00131Cereda, Bogliolo, Klersy, Lobascio, Masi et al., Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary referral hospital, Clini Nutrit,
doi:10.1016/j.clnu.2020.10.055Haraj, Aziz, Chadli, Dafir, Mjabber et al., Nutritional status assessment in patients with COVID-19 after discharge from the intensive care unit, Clin Nutr ESPEN,
doi:10.1016/j.clnesp.2020.09.214Hofer, Münzker, Schwetz, Ulbing, Hutz et al., Testicular synthesis and vitamin D action, J Clin Endocrinol Metab,
doi:10.1210/jc.2014-1690Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8Li, Zai, Zhao, Nie, Li et al., Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2, J Med Virol,
doi:10.1002/jmv.25731Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science,
doi:10.1126/science.1123933Maghbooli, Sahraian, Ebrahimi, Pazoki, Kafan et al., Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS ONE,
doi:10.1371/journal.pone.0239799Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ,
doi:10.1136/bmj.i6583Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study, FEBS J,
doi:10.1111/febs.15495Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J Med Virol,
doi:10.1002/jmv.26360Orchard, Baldry, Nasim-Mohi, Monck, Saeed et al., Vitamin-D levels and intensive care unit outcomes of a cohort of critically ill COVID-19 patients, Clin Chem Lab Med,
doi:10.1515/cclm-2020-1567Papadopoulos, Li, Samplaski, Why does COVID-19 kill more elderly men than women? Is there a role for testosterone?, Andrology,
doi:10.1111/andr.12868Pilz, Frisch, Koertke, Kuhn, Dreier et al., Effect of vitamin D supplementation on testosterone levels in men, Horm Metab Res,
doi:10.1055/s-0030-1269854Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D deficiency and outcome of COVID-19 patients, Nutrients,
doi:10.3390/nu12092757Rhodes, Subramanian, Laird, Kenny, Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity, Aliment Pharmacol Ther,
doi:10.1111/apt.15777Sanghera, Sapkota, Aston, Blackett, Vitamin D Status, Gender differences, and cardiometabolic health disparities, Ann Nutr Metab,
doi:10.1159/000458765Sengupta, Majumder, Majumder, Role of vitamin D in treating COVID-19-associated coagulopathy: problems and perspectives, Mol Cell Biochem,
doi:10.1007/s11010-021-04093-6Shakoor, Feehan, Dhaheri, Ali, Platat et al., Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?, Maturitas,
doi:10.1016/j.maturitas.2020.08.003Smet, Smet, Herroelen, Gryspeerdt, Martens, Serum 25(OH)D level on hospital admission associated with COVID-19 stage and mortality, Am J Clin Pathol,
doi:10.1093/ajcp/aqaa252Smolders, Van Den Ouweland, Geven, Pickkers, Kox, Letter to the editor: vitamin D deficiency in COVID-19: Mixing up cause and consequence, Metabolism,
doi:10.1016/j.metabol.2020.154434Sridhar, Rao, Multani, Jain, Assessment of prevalence of hypovitaminosis D in multiethnic population of the United Arab Emirates, J Adv Pharm Technol Res,
doi:10.4103/2231-4040.177202Taha, Abureesh, Alghamdi, Hassan, Cheikh et al., The relationship between vitamin D and infections including COVID-19: any hopes? IJGM,
doi:10.2147/IJGM.S317421Tan, Wang, Zhang, Ding, Huang et al., Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study, Signal Transduct Target Ther,
doi:10.1038/s41392-020-0159-1Teymoori-Rad, Shokri, Salimi, Marashi, The interplay between vitamin D and viral infections, Rev Med Virol,
doi:10.1002/rmv.2032Tsang, Chan, Cho, Yu, Yim et al., An update on COVID-19 pandemic: the epidemiology, pathogenesis, prevention and treatment strategies, Expert Rev Anti Infect Ther,
doi:10.1080/14787210.2021.1863146Xu, Yang, Chen, Luo, Zhang et al., Vitamin D alleviates lipopolysaccharide induced acute lung injury via regulation of the renin angiotensin system, Mol Med Rep,
doi:10.3892/mmr.2017.7546Zhou, Yang, Wang, Hu, Zhang et al., A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature,
doi:10.1038/s41586-020-2951-z
