Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study
Luca Gallelli, Gaia Chiara Mannino, Filippo Luciani, Alessandro De Sire, Elettra Mancuso, Pietro Gangemi, Lucio Cosco, Giuseppe Monea, Carolina Averta, Pasquale Minchella, Manuela Colosimo, Lucia Muraca, Federico Longhini, Antonio Ammendolia, Francesco Andreozzi, Giovambattista De Sarro, G&P Working Group † Erika Cione
Nutrients, doi:10.3390/nu13113932
Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D 3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D 3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D 3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D 3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D 3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH) 2 D 3 . Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH) 2 D 3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH) 2 D 3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.
References
Afzal, Bojesen, Nordestgaard, Low 25-Hydroxyvitamin D and risk of type 2 diabetes: A prospective cohort study and metaanalysis, Clin. Chem,
doi:10.1373/clinchem.2012.193003Bui, 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:10.1177/20503121211014073Buitrago, Boland, Caveolae and caveolin-1 are implicated in 1alpha,25(OH)2-vitamin D3-dependent modulation of Src, MAPK cascades and VDR localization in skeletal muscle cells, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2010.03.002Chamekh, Casimir, Editorial: Sexual dimorphism of the immune inflammatory response in infectious and non-infectious diseases, Front. Immunol,
doi:10.3389/fimmu.2019.00107D'avolio, Avataneo, Manca, Cusato, De Nicolò et al., 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359Ferraro, Calafiore, Dambruoso, Guidarini, De Sire, COVID-19 related fatigue: Which role for rehabilitation in post-COVID-19 patients? A case series, J. Med. Virol,
doi:10.1002/jmv.26717Fu, Cheng, Wu, Understanding SARS-CoV-2-mediated inflammatory responses: From mechanisms to potential therapeutic tools, Virol. Sin,
doi:10.1007/s12250-020-00207-4Gallelli, Escin: A review of its anti-edematous, anti-inflammatory, and venotonic properties, Drug Des. Dev. Ther,
doi:10.2147/DDDT.S207720Gallelli, Michniewicz, Cione, Squillace, Colosimo et al., 25-Hydroxy vitamin D detection using different analytic methods in patients with migraine, J. Clin. Med
Gimigliano, Moretti, De Sire, Calafiore, Iolascon, The combination of vitamin D deficiency and overweight affects muscle mass and function in older post-menopausal women, Aging Clin. Exp. Res,
doi:10.1007/s40520-018-0921-1Ginde, Mansbach, Camargo, Association between serum 25-Hydroxyvitamin D level and upper respiratory tract infection in the third national health and nutrition examination survey, Arch. Intern. Med,
doi:10.1001/archinternmed.2008.560Griffin, Hewison, Hopkin, Kenny, Quinton et al., Preventing vitamin D deficiency during the COVID-19 pandemic: UK definitions of vitamin D sufficiency and recommended supplement dose are set too low, Clin. Med,
doi:10.7861/clinmed.2020-0858Griffin, Hewison, Hopkin, Kenny, Quinton et al., Vitamin D and COVID-19: Evidence and recommendations for supplementation, R. Soc. Open Sci,
doi:10.1098/rsos.201912Holick, High prevalence of vitamin D inadequacy and implications for health, Mayo Clin. Proc. Marzo,
doi:10.4065/81.3.353Iolascon, Mauro, Fiore, Cisari, Benedetti et al., Can vitamin D deficiency influence muscle performance in postmenopausal women? A multicenter retrospective study, Eur. J. Phys. Rehabil. Med,
doi:10.23736/S1973-9087.17.04533-6Iorio, Ammendolia, Marotta, Ricardi, De Sire, A bond between rheumatic diseases and cancer in the elderly: The interleukin-6 pathway, Int. J. Rheum Dis,
doi:10.1111/1756-185X.14194Jin, He, Wu, Liu, Han et al., Gender differences in patients with COVID-19: Focus on severity and mortality, Front. Public Health,
doi:10.3389/fpubh.2020.00152Keller, Varela, Vazquez, Dangol, Damm et al., The role of vitamin D in the development of diabetes post gestational diabetes mellitus: A systematic literature review, Nutrients,
doi:10.3390/nu12061733Koenig, Buskiewicz, Huber, Age-Associated changes in estrogen receptor ratios correlate with increased female susceptibility to Coxsackievirus B3-Induced myocarditis, Front. Immunol,
doi:10.3389/fimmu.2017.01585Labudzynskyi, Shymanskyy, Veliky, Role of vitamin D3 in regulation of interleukin-6 and osteopontin expression in liver of diabetic mice, Eur. Rev. Med. Pharmacol. Sci
Lee, Li, Chan, Hollis, Lee et al., Circulating levels of vitamin D and colon and rectal cancer: The physicians' health study and a meta-analysis of prospective studies, Cancer Prev. Res,
doi:10.1158/1940-6207.CAPR-10-0289Liu, Li, Zhou, Guan, Xiang, Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?, J. Autoimmun,
doi:10.1016/j.jaut.2020.102452Liu, Zhou, Yang, The cytokine storm of severe influenza and development of immunomodulatory therapy, Cell Mol. Immunol,
doi:10.1038/cmi.2015.74Lu, Zhang, Ma, Yue, Zou et al., Link between community-acquired pneumonia and vitamin D levels in older patients, J. Gerontol. Geriatr,
doi:10.1007/s00391-017-1237-zMa, Zhou, Heianza, Qi, Habitual use of vitamin D supplements and risk of coronavirus disease 2019 (COVID-19) infection: A prospective study in UK Biobank, Am. J. Clin. Nutr,
doi:10.1093/ajcn/nqaa381Manion, Hullsiek, Wilson, Rhame, Kojic et al., Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons, PLoS ONE
Martín Giménez, Inserra, Tajer, Mariani, Ferder et al., Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment, Life Sci,
doi:10.1016/j.lfs.2020.117808Mauvais-Jarvis, Klein, Levin, Estradiol, progesterone, immunomodulation, and COVID-19 outcomes, Endocrinology,
doi:10.1210/endocr/bqaa127Mehta, Mcauley, Brown, Sanchez, Tattersall et al., HLH across speciality collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression, Lancet,
doi:10.1016/S0140-6736(20)30628-0Negrini, De Sire, Andrenelli, Lazzarini, Patrini et al., International multiprofessional steering committee of cochrane rehabilitation REH-COVER action. rehabilitation and COVID-19: The cochrane rehabilitation 2020 rapid living systematic review. update as of July 31st, Eur. J. Phys. Rehabil. Med,
doi:10.23736/S1973-9087.20.06539-9Osorio Landa, Pérez Díaz, Laguna Bárcenas, López Navarro, Abella Roa et al., Association of serum vitamin D levels with chronic disease and mortality, Nutr. Hosp
Perri, Pingitore, Cione, Vilardi, Perrone et al., Proliferative and anti-proliferative effects of retinoic acid at doses similar to endogenous levels in Leydig MLTC-1/R2C/TM-3 cells, Biochim. Biophys. Acta,
doi:10.1016/j.bbagen.2010.06.006Quesada-Gomez, Entrenas-Castillo, Bouillon, Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105719Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for Coronavirus disease 2019 (COVID-19): A Review, JAMA,
doi:10.1001/jama.2020.6019Siniscalchi, Lochner, Anticoli, Chirchiglia, De Sarro et al., What is the current role for vitamin D and the risk of stroke?, Curr. Neurovasc. Res,
doi:10.2174/1567202616666190412152948Torkildsen, Knappskog, Nyland, Myhr, Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis, Arch. Neurol,
doi:10.1001/archneur.65.6.809Umar, Sastry, Chouchane, Role of Vitamin D beyond the skeletal function: A Review of the molecular and clinical studies, Int. J. Mol. Sci,
doi:10.3390/ijms19061618White, Vitamin, Signaling, Infectious Diseases, and Regulation of Innate Immunity, Infect. Immun
Yan, Zhang, Cheng, Wang, Qin, Gender differences in vitamin D status in China, Med. Sci. Monit. Int. Med. J. Exp. Clin. Res,
doi:10.12659/MSM.916326
