Decreased serum vitamin D level as a prognostic marker in patients with COVID-19 (preprint)

Background: The corona virus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2, is still localized outbreak and has resulted in a high rate of infection and severe disease in older patients with comorbidities. The vitamin D status of the population has been found to be an important factor that could influence outcome of COVID-19. However, whether vitamin D can lessen the symptoms or severity of COVID-19 still remains controversial. Methods: A total of 719 patients with confirmed COVID-19 were enrolled retrospectively in this study from April 13 to June 6, 2022 at Shanghai Forth People's Hospital. The circulating levels of 25(OH)D3, inflammatory factors, and clinical parameters were assayed. Time to viral RNA clearance (TVRC), classification and prognosis of COVID-19 were used to evaluate the severity of COVID-19 infection. Results: The median age was 76 years (interquartile range, IQR, 64.5-84.6), 44.1% of patients were male, and the TVRC was 11 days (IQR, 7-16) in this population. The median level of 25(OH)D3 was 27.15 (IQR, 19.31-38.89) nmol/L. Patients with lower serum 25(OH)D3 had prolonged time to viral clearance, more obvious inflammatory response, more severe respiratory symptoms and higher risks of impaired hepatic and renal function. Multiple regression analyses revealed that serum 25(OH)D3 level was negatively associated with TVRC independently. ROC curve showed the serum vitamin D level could predict the severity classification and prognosis of COVID-19 significantly.Conclusions: Serum 25(OH)D3 level is independently associated with the severity of COVID-19 in elderly, and it could be used as a predictor of the severity of COVID-19. In addition, supplementation with vitamin D might provide beneficial effects in old patients with COVID-19.

[1]  R. Gibbons,et al.  Association between vitamin D supplementation and COVID-19 infection and mortality , 2022, Scientific Reports.

[2]  V. Baklaushev,et al.  Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU , 2022, Scientific Reports.

[3]  David A. Jolliffe,et al.  Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT) , 2022, BMJ.

[4]  C. Mantzoros,et al.  Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients , 2021, Mayo Clinic Proceedings.

[5]  M. Rubin,et al.  Vitamin D Status and COVID-19 Clinical Outcomes in Hospitalized Patients , 2020, Endocrine research.

[6]  N. Sachdeva,et al.  Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study) , 2020, Postgraduate Medical Journal.

[7]  G. Remuzzi,et al.  Immunity, endothelial injury and complement-induced coagulopathy in COVID-19 , 2020, Nature Reviews Nephrology.

[8]  S. P. Singh,et al.  Microstructure, pathophysiology, and potential therapeutics of COVID‐19: A comprehensive review , 2020, Journal of medical virology.

[9]  Fiona Mitchell.  Vitamin-D and COVID-19: do deficient risk a poorer outcome? , 2020, The Lancet Diabetes & Endocrinology.

[10]  Fang Lei,et al.  Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes , 2020, Cell Metabolism.

[11]  R. José,et al.  COVID-19 cytokine storm: the interplay between inflammation and coagulation , 2020, The Lancet Respiratory Medicine.

[12]  D. McGonagle,et al.  The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease , 2020, Autoimmunity Reviews.

[13]  R. Pranata,et al.  Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression , 2020, Journal of the renin-angiotensin-aldosterone system : JRAAS.

[14]  R. Trimble.  COVID-19 Dashboard , 2020 .

[15]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[16]  Ruchong Chen,et al.  Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China , 2020, The Lancet Oncology.

[17]  S. Pilz,et al.  Vitamin D deficiency 2.0: an update on the current status worldwide , 2020, European Journal of Clinical Nutrition.

[18]  H. Bischoff-Ferrari,et al.  MANAGEMENT OF ENDOCRINE DISEASE: Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency; a position statement of the European Calcified Tissue Society. , 2019, European journal of endocrinology.

[19]  J. Royo,et al.  Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis. , 2018, Gene.

[20]  Vladyslav Povoroznyuk,et al.  Vitamin D supplementation guidelines , 2018, The Journal of Steroid Biochemistry and Molecular Biology.

[21]  B. Jiang,et al.  Serum vitamin D levels of the natural population in eastern China , 2017 .

[22]  David A. Jolliffe,et al.  Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data , 2017, British Medical Journal.

[23]  Jianhua Fu,et al.  Vitamin D/VDR signaling attenuates lipopolysaccharide-induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier , 2015, Molecular medicine reports.

[24]  M. Mangin,et al.  Inflammation and vitamin D: the infection connection , 2014, Inflammation Research.

[25]  M. Holick,et al.  Vitamin D for health: a global perspective. , 2013, Mayo Clinic proceedings.

[26]  M. Holick.  Vitamin D and sunlight: strategies for cancer prevention and other health benefits. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[27]  R. Heaney.  Vitamin D in health and disease. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[28]  J. Adams,et al.  Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response , 2006, Science.

[29]  B. Dawson-Hughes,et al.  Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. , 2002, Bone.

[30]  M. Galligan,et al.  The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. , 2000, Molecular endocrinology.

[31]  H. van den Berg,et al.  Serum vitamin D concentrations among elderly people in Europe , 1995, The Lancet.

[32]  D. Prabhakaran,et al.  Independent association of severe vitamin D deficiency as a risk of acute myocardial infarction in Indians. , 2015, Indian heart journal.

[33]  B. Clarke,et al.  Vitamin D insufficiency. , 2011, Mayo Clinic proceedings.

[34]  G. Rook,et al.  Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. , 1986, Immunology.