Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients

Angeliki M Angelidi, Matthew J Belanger, Michael K Lorinsky, Dimitrios Karamanis, Natalia Chamorro-Pareja, Jennifer Ognibene, Leonidas Palaiodimos, Christos S Mantzoros, Angeliki M Angelidi, Matthew J Belanger, Michael K Lorinsky, Dimitrios Karamanis, Natalia Chamorro-Pareja, Jennifer Ognibene, Leonidas Palaiodimos, Christos S Mantzoros

Abstract

Objective: To explore the possible associations of serum 25-hydroxyvitamin D [25(OH)D] concentration with coronavirus disease 2019 (COVID-19) in-hospital mortality and need for invasive mechanical ventilation.

Patients and methods: A retrospective, observational, cohort study was conducted at 2 tertiary academic medical centers in Boston and New York. Eligible participants were hospitalized adult patients with laboratory-confirmed COVID-19 between February 1, 2020, and May 15, 2020. Demographic and clinical characteristics, comorbidities, medications, and disease-related outcomes were extracted from electronic medical records.

Results: The final analysis included 144 patients with confirmed COVID-19 (median age, 66 years; 64 [44.4%] male). Overall mortality was 18%, whereas patients with 25(OH)D levels of 30 ng/mL (to convert to nmol/L, multiply by 2.496) and higher had lower rates of mortality compared with those with 25(OH)D levels below 30 ng/mL (9.2% vs 25.3%; P=.02). In the adjusted multivariable analyses, 25(OH)D as a continuous variable was independently significantly associated with lower in-hospital mortality (odds ratio, 0.94; 95% CI, 0.90 to 0.98; P=.007) and need for invasive mechanical ventilation (odds ratio, 0.96; 95% CI, 0.93 to 0.99; P=.01). Similar data were obtained when 25(OH)D was studied as a continuous variable after logarithm transformation and as a dichotomous (<30 ng/mL vs ≥30 ng/mL) or ordinal variable (quintiles) in the multivariable analyses.

Conclusion: Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.

Copyright © 2021 Mayo Foundation for Medical Education and Research. All rights reserved.

References

    1. World Health Organization Coronavirus disease 2019 (COVID-19): weekly epidemiological update.
    1. Chakhtoura M., Napoli N., El Hajj Fuleihan G. Commentary: myths and facts on vitamin D amidst the COVID-19 pandemic. Metabolism. 2020;109:154276.
    1. Pham H., Rahman A., Majidi A., Waterhouse M., Neale R.E. Acute respiratory tract infection and 25-hydroxyvitamin D concentration: a systematic review and meta-analysis. Int J Environ Res Public Health. 2019;16(17):3020.
    1. Ginde A.A., Camargo C.A., Jr., Shapiro N.I. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18(5):551–554.
    1. Nair P., Venkatesh B., Center J.R. Vitamin D deficiency and supplementation in critical illness—the known knowns and known unknowns. Crit Care. 2018;22(1):276.
    1. Manson J.E., Bassuk S.S. Commentary. Eliminating vitamin D deficiency during the COVID-19 pandemic: a call to action. Metabolism. 2020;112:154322.
    1. Rhodes J.M., Subramanian S., Laird E., Kenny R.A. 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. 2020;51(12):1434–1437.
    1. Ilie P.C., Stefanescu S., Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res. 2020;32(7):1195–1198.
    1. D'Avolio A., Avataneo V., Manca A. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients. 2020;12(5):1359.
    1. Hastie C.E., Mackay D.F., Ho F. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020;14(4):561–565.
    1. Raisi-Estabragh Z., McCracken C., Bethell M.S. Greater risk of severe COVID-19 in Black, Asian and minority ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank. J Public Health (Oxf) 2020;42(3):451–460.
    1. Meltzer D.O., Best T.J., Zhang H., Vokes T., Arora V., Solway J. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open. 2020;3(9):e2019722.
    1. Freeman J., Wilson K., Spears R., Shalhoub V., Sibley P. Performance evaluation of four 25-hydroxyvitamin D assays to measure 25-hydroxyvitamin D2. Clin Biochem. 2015;48(16-17):1097–1104.
    1. Centers for Disease Control and Prevention Vitamin D standardization-certification program.
    1. Holick M.F., Chen T.C. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S–1086S.
    1. Palacios C., Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144(pt A):138–145.
    1. Giustina A., Adler R.A., Binkley N. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab. 2019;104(2):234–240.
    1. Dancer R.C., Parekh D., Lax S. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS) Thorax. 2015;70(7):617–624.
    1. Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F.P. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–374.
    1. Holick M.F., Binkley N.C., Bischoff-Ferrari H.A. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930.
    1. Demer L.L., Hsu J.J., Tintut Y. Steroid hormone vitamin D: Implications for cardiovascular disease. Circ Res. 2018;122(11):1576–1585.
    1. Lemire J.M., Adams J.S., Kermani-Arab V., Bakke A.C., Sakai R., Jordan S.C. 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol. 1985;134(5):3032–3035.
    1. Cantorna M.T., Snyder L., Lin Y.D., Yang L. Vitamin D and 1,25(OH)2D regulation of T cells. Nutrients. 2015;7(4):3011–3021.
    1. Jeffery L.E., Burke F., Mura M. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 2009;183(9):5458–5467.
    1. Grant W.B., Lahore H., McDonnell S.L. Evidence that vitamin D supplementation Could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988.
    1. Greiller C.L., Martineau A.R. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. 2015;7(6):4240–4270.
    1. Liu P.T., Stenger S., Li H. Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science. 2006;311(5768):1770–1773.
    1. Adams J.S., Ren S., Liu P.T. Vitamin D–directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009;182(7):4289–4295.
    1. Laaksi I. Vitamin D and respiratory infection in adults. Proc Nutr Soc. 2012;71(1):90–97.
    1. Herr C., Shaykhiev R., Bals R. The role of cathelicidin and defensins in pulmonary inflammatory diseases. Expert Opin Biol Ther. 2007;7(9):1449–1461.
    1. Martín Giménez V.M., Inserra F., Tajer C.D. Lungs as target of COVID-19 infection: protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment. Life Sci. 2020;254:117808.
    1. Malek Mahdavi A. A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: implications for a potential treatment for COVID-19. Rev Med Virol. 2020;30(5):e2119.
    1. Rhodes J.M., Subramanian S., Laird E., Griffin G., Kenny R.A. Perspective: Vitamin D deficiency and COVID-19 severity—plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis. J Intern Med. 2020;289(1):97–115.
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239–1242.
    1. Docherty A.B., Harrison E.M., Green C.A. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;369:m1985.
    1. Palaiodimos L., Kokkinidis D.G., Li W. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism. 2020;108:154262.
    1. Langlois P.L., Szwec C., D'Aragon F., Heyland D.K., Manzanares W. Vitamin D supplementation in the critically ill: a systematic review and meta-analysis. Clin Nutr. 2018;37(4):1238–1246.
    1. Putzu A., Belletti A., Cassina T. Vitamin D and outcomes in adult critically ill patients. A systematic review and meta-analysis of randomized trials. J Crit Care. 2017;38:109–114.
    1. Ginde A.A., Brower R.G., Caterino J.M. Early high-dose vitamin D3 for critically ill, vitamin D–deficient patients. N Engl J Med. 2019;381(26):2529–2540.
    1. Martineau A.R., Jolliffe D.A., Hooper R.L. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583.

Source: PubMed

3
Sottoscrivi