Possible Impact of Vitamin D Status and Supplementation on SARS-CoV-2 Infection Risk and COVID-19 Symptoms in a Cohort of Patients with Inflammatory Bowel Disease
Amedeo De Nicolò, Jessica Cusato, Cristina Bezzio, Simone Saibeni, Marta Vernero, Michela Disabato, Gian Paolo Caviglia, Alice Ianniello, Alessandra Manca, Antonio D’avolio, Davide Giuseppe Ribaldone
Nutrients, doi:10.3390/nu15010169
The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (antispike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.
Conflicts of Interest: The authors declare no conflict of interest.
References
Anbarcioglu, Kirtiloglu, Ozturk, Kolbakir, Acikgoz et al., Vitamin D deficiency in patients with aggressive periodontitis, Oral Dis,
doi:10.1111/odi.12968Arboleda, Urcuqui-Inchima, Vitamin, Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics? Front, Immunol,
doi:10.3389/fimmu.2020.01523Arora, Patel, Nicol, Field, Restori et al., Vitamin D and the Ability to Produce 1,25(OH)(2)D Are Critical for Protection from Viral Infection of the Lungs, Nutrients,
doi:10.3390/nu14153061Azrielant, Shoenfeld, Vitamin D and the Immune System, Isr. Med. Assoc. J
Balestrieri, Ribolsi, Guarino, Emerenziani, Altomare et al., Nutritional Aspects in Inflammatory Bowel Diseases, Nutrients,
doi:10.3390/nu12020372Benskin, A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency, Front. Public Health,
doi:10.3389/fpubh.2020.00513Bezzio, Armuzzi, Furfaro, Ardizzone, Milla et al., Therapies for inflammatory bowel disease do not pose additional risks for adverse outcomes of SARS-CoV-2 infection: An IG-IBD study, Aliment. Pharmacol. Ther,
doi:10.1111/apt.16663Bezzio, Saibeni, Variola, Allocca, Massari et al., Outcomes of COVID-19 in 79 patients with IBD in Italy: An IG-IBD study, Gut,
doi:10.1136/gutjnl-2020-321411Boglione, Cusato, De Nicolo, Cariti, Di Perri et al., Role of CYP27B1+2838 promoter polymorphism in the treatment of chronic hepatitis B HBeAg negative with PEG-interferon, J. Viral Hepat,
doi:10.1111/jvh.12288Calcagno, Ghisetti, Emanuele, Trunfio, Faraoni et al., Risk for SARS-CoV-2 Infection in Healthcare Workers, Emerg. Infect. Dis,
doi:10.3201/eid2701.203027Cascella, Rajnik, Aleem, Dulebohn, Di Napoli et al., Evaluation, and Treatment of Coronavirus (COVID-19
Castillo, Entrenas Costa, Vaquero Barrios, Alcala Diaz, Lopez Miranda et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105751Chauss, Freiwald, Mcgregor, Yan, Wang et al., Autocrine vitamin D signaling switches off pro-inflammatory programs of TH1 cells, Nat. Immunol,
doi:10.1038/s41590-021-01080-3Coperchini, Ricci, Croce, Denegri, Ruggiero et al., Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: A pilot study, Endocrine,
doi:10.1007/s12020-021-02807-wCourbebaisse, Cavalier, Vitamin, in 2020: An Old Pro-Hormone with Potential Effects beyond Mineral Metabolism, Nutrients,
doi:10.3390/nu12113378Cusato, Allegra, Boglione, De Nicolo, Baietto et al., Vitamin D pathway gene variants and HCV-2/3 therapy outcomes, Antivir. Ther,
doi:10.3851/IMP2853D'avolio, Avataneo, Manca, Cusato, De Nicolo et al., 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359De Nicolò, Avataneo, Cusato, Palermiti, Mula et al., Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening, Diagnostics,
doi:10.3390/diagnostics11050869Dickie, Church, Coulthard, Mathews, Emery et al., Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes, Rheumatology,
doi:10.1093/rheumatology/keq124Dipasquale, Lo Presti, Milani, Corsello, Agostoni et al., Vitamin D in Prevention of Autoimmune Diseases, Front. Biosci. Landmark,
doi:10.31083/j.fbl2710288Dragasevic, Stankovic, Kotur, Milutinovic, Milovanovic et al., Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease, Life,
doi:10.3390/life12101623Ecco, Update on COVID-19 and IBD
Gallelli, Mannino, Luciani, De Sire, Mancuso et al., 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, Nutrients,
doi:10.3390/nu13113932Gibbons, Norton, Mccullough, Meltzer, Lavigne et al., Association between vitamin D supplementation and COVID-19 infection and mortality, Sci. Rep,
doi:10.1038/s41598-022-24053-4Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2011-0385Holick, The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention, Rev. Endocr. Metab. Disord,
doi:10.1007/s11154-017-9424-1Huang, Lian, Song, Ma, Lian et al., Clinical features of severe patients infected with 2019 novel coronavirus: A systematic review and meta-analysis, Ann. Transl. Med,
doi:10.21037/atm-20-2124Jain, Chaurasia, Sengar, Singh, Mahor et al., Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers, Sci. Rep,
doi:10.1038/s41598-020-77093-zJin, Lian, Hu, Gao, Zheng et al., Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms, Gut,
doi:10.1136/gutjnl-2020-320926Maaser, Sturm, Vavricka, Kucharzik, Fiorino et al., ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications, J. Crohns Colitis,
doi:10.1093/ecco-jcc/jjy113Maghbooli, 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.0239799Matheu, Back, Mondoc, Issazadeh-Navikas, Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: Enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease, J. Allergy Clin. Immunol,
doi:10.1016/s0091-6749Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics with COVID-19 Test Results, JAMA Netw. Open,
doi:10.1001/jamanetworkopen.2020.19722Munshi, 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.26360Murai, Fernandes, Antonangelo, Gualano, Pereira, Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19, Clinics,
doi:10.6061/clinics/2021/e3549Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2020.26848Sanson, De Nicolo, Zerbato, Segat, Koncan et al., A combined role for low vitamin D and low albumin circulating levels as strong predictors of worse outcome in COVID-19 patients, Ir. J. Med. Sci,
doi:10.1007/s11845-022-02952-9Sekine, Perez-Potti, Rivera-Ballesteros, Stralin, Gorin et al., Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19, Cell,
doi:10.1016/j.cell.2020.08.017Siew, Hilmi, Blake, Bhayat, Adsul et al., Low Frequency of Opportunistic Infections in Patients Receiving Vedolizumab in Clinical Trials and Post-Marketing Setting, Inflamm. Bowel Dis,
doi:10.1093/ibd/izy153Villasis-Keever, Lopez-Alarcon, Miranda-Novales, Zurita-Cruz, Barrada-Vazquez et al., Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial, Arch. Med. Res,
doi:10.1016/j.arcmed.2022.04.003Wang, Wang, Li, Chen, Han et al., Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds with One Stone, ACS Infect. Dis,
doi:10.1021/acsinfecdis.1c00096Wu, Chen, Cai, Xia, Zhou et al., Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China, JAMA Intern. Med,
doi:10.1001/jamainternmed.2020.0994Wu, Liu, Deng, The Role of Vitamin D in Immune System and Inflammatory Bowel Disease, J. Inflamm. Res,
doi:10.2147/JIR.S363840Zhang, Leung, Richers, Liu, Remigio et al., Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1, J. Immunol,
doi:10.4049/jimmunol.1102412Zhang, Wu, Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis, Neurosci. Bull,
doi:10.1007/s12264-010-0731-8Zhao, Zhang, Wu, Li, Liu et al., Protective role of 1,25(OH)2 vitamin D3 in the mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice, BMC Gastroenterol,
doi:10.1186/1471-230X-12-57Zurita-Cruz, Fonseca-Tenorio, Villasis-Keever, Lopez-Alarcon, Parra-Ortega et al., Efficacy and safety of vitamin D supplementation in hospitalized COVID-19 pediatric patients: A randomized controlled trial, Front. Pediatr,
doi:10.3389/fped.2022.943529
