Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults

Barrett et al., Nutrients, doi:10.3390/nu14163252

Aug 2022

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Prospective study of 232 hospitalized COVID-19 pneumonia patients, showing higher risk of mortality with vitamin D deficiency.

This is the 142nd of 184 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 712 vigintillion).

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risk of death, 78.4% lower, OR 0.22, p = 0.006, high D levels (≥30nmol/L) 144, low D levels (<30nmol/L) 88, adjusted per study, inverted to make OR<1 favor high D levels (≥30nmol/L), multivariable, RR approximated with OR.

risk of ICU admission, 15.3% lower, OR 0.85, p = 0.63, high D levels (≥30nmol/L) 144, low D levels (<30nmol/L) 88, adjusted per study, inverted to make OR<1 favor high D levels (≥30nmol/L), multivariable, RR approximated with OR.

risk of progression, 52.6% lower, OR 0.47, p = 0.12, high D levels (≥30nmol/L) 144, low D levels (<30nmol/L) 88, adjusted per study, inverted to make OR<1 favor high D levels (≥30nmol/L), extended oxygen requirement, multivariable, RR approximated with OR.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Barrett et al., 9 Aug 2022, prospective, Ireland, peer-reviewed, mean age 56.0, 19 authors, study period March 2020 - April 2021.

Contact: johnfaul@rcsi.ie (corresponding author).

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Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults

Robert Barrett, Modar Youssef, Irfan Shah, Julia Ioana, Abdullah Al Lawati, Abdullah Bukhari, Suzanne Hegarty, Liam J Cormican, Eoin Judge, Conor M Burke, Catriona Cody, Joseph Feely, Katrina Hutchinson, William Tormey, Eoghan O’ Neill, Aoife O’ Shea, Meabh Connolly, Daniel M A Mccartney, John L Faul

Nutrients, doi:10.3390/nu14163252

COVID-19 and a low vitamin D state share common risk factors, which might explain why vitamin D deficiency has been linked with higher COVID-19 mortality. Moreover, measures of serum vitamin D may become lower during systemic inflammatory responses, further confounding the association via reverse causality. In this prospective study (recruited over 12 months), we examined whether the association between a low vitamin D state and in-hospital mortality due to SARS-CoV-2 pneumonia in unvaccinated subjects is explained by (i) the presence of shared risk factors (e.g., obesity, advanced age) or (ii) a reduction in serum 25(OH)D due to COVID-19 (i.e., reverse causality). In this cohort of 232 (mean age = 56 years) patients (all had SARS-CoV-2 diagnosed via PCR AND required supplemental oxygen therapy), we failed to find an association between serum vitamin D and levels of CRP, or other inflammatory markers. However, the hazard ratio for mortality for subjects over 70 years of age (13.2) and for subjects with a serum 25(OH)D level less than 30 nmol•L −1 (4.6) remained significantly elevated even after adjustment for gender, obesity and the presence of diabetes mellitus. Subjects <70 years and >70 years had significantly higher mortality with a serum 25(OH)D less than 30 nmol•L −1 (11.8% and 55%), than with a serum 25(OH)D greater than 30 nmol•L −1 (2.2% and 25%). Unvaccinated Caucasian adults with a low vitamin D state have higher mortality due to SARS CoV-2 pneumonia, which is not explained by confounders and is not closely linked with elevated serum CRP.

References

Akbar, 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.2021.660420

Angelidi, 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.2021.01.001

Annweiler, Corvaisier, Gautier, Dubée, Legrand et al., Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study, Nutrients, doi:10.3390/nu12113377

Baktash, Hosack, Patel, Shah, Kandiah et al., Vitamin D status and outcomes for hospitalised older patients with COVID-19, Postgrad Med. J, doi:10.1136/postgradmedj-2020-138712

Benskin, 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.2020.00513

Bian, Jin, Shou, Effects of Monthly Intramuscular High-Dose Vitamin D2 on Serum 25-Hydroxyvitamin D and Immune Parameters in Very Elderly Chinese Patients with Vitamin D Deficiency, Int. J. Endocrinol, doi:10.1155/2021/1343913

Black, Walton, Flynn, Cashman, Kiely, Small Increments in Vitamin D Intake by Irish Adults over a Decade Show That Strategic Initiatives to Fortify the Food Supply Are Needed, J. Nutr, doi:10.3945/jn.114.209106

Borsche, Glauner, Von Mendel, COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis, Nutrients, doi:10.3390/nu13103596

Campi, Gennari, Merlotti, Mingiano, Frosali et al., Vitamin D and COVID-19 severity and related mortality: A prospective study in Italy, BMC Infect. Dis, doi:10.1186/s12879-021-06281-7

Cashman, Muldowney, Mcnulty, Nugent, Fitzgerald et al., Vitamin D status of Irish adults: Findings from the National Adult Nutrition Survey, Br. J. Nutr, doi:10.1017/S0007114512003212

Charoenngam, Holick, Immunologic Effects of Vitamin D on Human Health and Disease, Nutrients, doi:10.3390/nu12072097

De Smet, De 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/aqaa252

Efird, Anderson, Jindal, Redding, Thompson et al., The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2, Int. J. Environ. Res. Public Health, doi:10.3390/ijerph19010447

Faul, Kerley, Love, O'neill, Cody et al., Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection, Ir. Med. J

Griffin, Wall, Blake, Griffin, Robinson et al., Higher risk of vitamin D insufficiency/deficiency for rural than urban dwellers, J. Steroid. Biochem. Mol. Biol, doi:10.1016/j.jsbmb.2019.105547

Haussler, Jurutka, Mizwicki, Norman, Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2 vitamin D3: Genomic and non-genomic mechanisms, Best Pract. Res. Clin. Endocrinol. Metab, doi:10.1016/j.beem.2011.05.010

Hii, Ferrante, The Non-Genomic Actions of Vitamin, D. Nutrients, doi:10.3390/nu8030135

Hyppönen, Berry, Cortina-Borja, Power, 25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: A cross sectional analysis in the 1958 British Birth Cohort, PLoS ONE, doi:10.1371/journal.pone.0010801

Israel, Cicurel, Feldhamer, Stern, Dror et al., Vitamin D deficiency is associated with higher risks for SARS-CoV-2 infection and COVID-19 severity: A retrospective case-control study, Intern. Emerg. Med, doi:10.1007/s11739-021-02902-w

Jain, 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-z

Jeong, Vacanti, Systemic vitamin intake impacting tissue proteomes, Nutr. Metab, doi:10.1186/s12986-020-00491-7

Jevalikar, Mithal, Singh, Sharma, Farooqui et al., Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19, Sci. Rep, doi:10.1038/s41598-021-85809-y

Kazemi, Mohammadi, Aghababaee, Golzarand, Clark et al., Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis, Adv. Nutr, doi:10.1093/advances/nmab012

Laird, O'halloran, Carey, Healy, O'connor et al., The prevalence of vitamin D deficiency and the determinants of 25(OH)D concentration in older Irish adults: Data from the Irish Longitudinal Study on Ageing (TILDA), J. Gerontol. A Biol. Sci. Med. Sci, doi:10.1093/gerona/glx168

Lippi, Plebani, Henry, Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis, Clin. Chim. Acta, doi:10.1016/j.cca.2020.03.022

Patchen, Clark, Gaddis, Hancock, Cassano, Genetically predicted serum vitamin D and COVID-19: A Mendelian randomisation study, BMJ Nutr. Prev. Health, doi:10.1136/bmjnph-2021-000255

Petrelli, Luciani, Perego, Dognini, Colombelli et al., Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies, J. Steroid Biochem. Mol. Biol, doi:10.1016/j.jsbmb.2021.105883

Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients, doi:10.3390/nu12092757

Reid, Bolland, Grey, Effects of vitamin D supplements on bone mineral density: A systematic review and metaanalysis, Lancet, doi:10.1016/S0140-6736(13)61647-5

Rhodes, Subramanian, Laird, Griffin, Kenny, Perspective: Vitamin D deficiency and COVID-19 severityplausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis, J. Intern. Med, doi:10.1111/joim.13149

Romero-Ortuno, Cogan, Browne, Healy, Casey et al., Seasonal variation of serum vitamin D and the effect of vitamin D supplementation in Irish community-dwelling older people, Age Ageing, doi:10.1093/ageing/afq138

Rostami, Mansouritorghabeh, D-dimer level in COVID-19 infection: A systematic review, Expert Rev. Hematol, doi:10.1080/17474086.2020.1831383

Skversky, Kumar, Abramowitz, Kaskel, Melamed, Association of glucocorticoid use and low 25-hydroxyvitamin D levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006, J. Clin. Endocrinol. Metab, doi:10.1210/jc.2011-1600

Smolders, 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.2020.154434

Sunnetcioglu, Sunnetcioglu, Gurbuz, Bedirhanoglu, Erginoguz et al., Serum 25(OH)D Deficiency and High D-Dimer Levels are Associated with COVID-19 Pneumonia, Clin Lab, doi:10.7754/Clin.Lab.2020.201050

The, Group, Dexamethasone in Hospitalized Patients with COVID-19, N. Engl. J. Med, doi:10.1056/NEJMoa2021436

Vassiliou, Jahaj, Pratikaki, Orfanos, Dimopoulou et al., Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort, Nutrients, doi:10.3390/nu12123773

Walsh, Mccartney, Laird, Mccarroll, Byrne et al., Understanding a Low Vitamin D State in the Context of COVID-19, Front. Pharmacol, doi:10.3389/fphar.2022.835480

Wang, C-reactive protein levels in the early stage of COVID-19, Médecine Mal. Infect, doi:10.1016/j.medmal.2020.03.007

Williamson, Walker, Bhaskaran, Bacon, Bates et al., Factors associated with COVID-19-related death using OpenSAFELY, Nature, doi:10.1038/s41586-020-2521-4

Yao, Cao, Wang, Shi, Liu et al., D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: A case control study, J. Intensive Care, doi:10.1186/s40560-020-00466-z

Zhang, Huang, Administration with corticosteroid relieving pain following total knee arthroplasty: A meta-analysis, Medicine, doi:10.1097/MD.0000000000023567

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