Hospital Outcomes in Patients Hospitalized for COVID-19 Pneumonia: The Effect of SARS-CoV-2 Vaccination and Vitamin D Status
Martyna Sanecka, Modar Youssef, Mohammad Abdulsalam, Syed F Raza, Abdul Qadeer, Julia Ioana, Alya Aldoresi, Syed I Shah, Abdul Al Lawati, Joseph Feely, William P Tormey, Eoghan O’neill, Liam J Cormican, Eoin P Judge, Daniel M A Mccartney, John L Faul
Nutrients, doi:10.3390/nu15132976
SARS-CoV-2 vaccination promises to improve outcomes for patients with COVID-19 pneumonia (most notably those with advanced age and at high risk for severe disease). Here, we examine serum 25-Hydroxyvitamin D (25(OH)D) status and outcomes in both old (>70 years) and young vaccinated (n = 80) and unvaccinated (n = 91) subjects, who were hospitalized due to COVID-19 pneumonia in a single center (Connolly Hospital Dublin). Outcomes included ICU admission and mortality. Serum 25(OH)D levels were categorized as D30 (<30 nmol/L), D40 (30-49.99 nmol/L) and D50 (≥50 nmol/L). In multivariate analyses, D30 was independently associated with ICU admission (OR: 6.87 (95% CI: 1.13-41.85) (p = 0.036)) and mortality (OR: 24.81 (95% CI: 1.57-392.1) (p = 0.023)) in unvaccinated patients, even after adjustment for major confounders including age, sex, obesity and pre-existing diabetes mellitus. While mortality was consistently higher in all categories of patients over 70 years of age, the highest observed mortality rate of 50%, seen in patients over 70 years with a low vitamin D state (D30), appeared to be almost completely corrected by either vaccination, or having a higher vitamin D state, i.e., mortality was 14% for vaccinated patients over 70 years with D30 and 16% for unvaccinated patients over 70 years with a 25(OH)D level greater than 30 nmol/L. We observe that high mortality from COVID-19 pneumonia occurs in older patients, especially those who are unvaccinated or have a low vitamin D state. Recent vaccination or having a high vitamin D status are both associated with reduced mortality, although these effects do not fully mitigate the mortality risk associated with advanced age.
Author Contributions: M.S., data processing, data analysis, data interpretation, manuscript drafts; J.L.F. and D.M.A.M., study design, data interpretation, manuscript drafts, data analysis; M.Y., M.A., S.F.R., A.Q., J.I., A.A., S.I.S., J.F., W.P.T., E.O., L.J.C., E.P.J. and A.A.L. data collection, processing, analysis and interpretation; J.L.F., study design, data collection, processing, analysis and interpretation, manuscript drafts. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Connolly Hospital Dublin. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflict of interest.
References
Andrews, Stowe, Kirsebom, Toffa, Rickeard et al., COVID-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant, N. Engl. J. Med,
doi:10.1056/NEJMoa2119451Angelidi, 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.2021.01.001Argano, Mallaci Bocchio, Natoli, Scibetta, Lo Monaco et al., Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis, Pharmaceuticals,
doi:10.3390/ph16010130Barrett, Youssef, Shah, Ioana, Lawati et al., Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults, Nutrients,
doi:10.3390/nu14163252Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms In Endocrinology: Vitamin D and COVID-19,
doi:10.1530/EJE-20-0665Borsche, 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/nu13103596Cashman, Dowling, Škrabáková, Gonzalez-Gross, Valtueña et al., Vitamin D deficiency in Europe: Pandemic?, Am. J. Clin. Nutr,
doi:10.3945/ajcn.115.120873Chauss, Freiwald, Mcgregor, Yan, Wang et al., Autocrine vitamin D signaling switches off pro-inflammatory programs of T H 1 cells, Nat. Immunol,
doi:10.1038/s41590-021-01080-3Chen, Mei, Xie, Yuan, Ma et al., Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: A meta-analysis and GRADE assessment of cohort studies and RCTs, Nutr. J,
doi:10.1186/s12937-021-00744-yChiodini, Gatti, Soranna, Merlotti, Mingiano et al., Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes, Front. Public Health,
doi:10.3389/fpubh.2021.736665Chiu, Tsai, Wu, Zheng, Yang et al., Putative Role of Vitamin D for COVID-19 Vaccination, Int. J. Mol. Sci,
doi:10.3390/ijms22168988D'ecclesiis, Gavioli, Martinoli, Raimondi, Chiocca et al., Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis, PLoS ONE,
doi:10.1371/journal.pone.0268396Dror, Morozov, Daoud, Namir, Yakir et al., Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness, PLoS ONE,
doi:10.1371/journal.pone.0263069Griffin, Haddix, Danza, Fisher, Koo et al., SARS-CoV-2 Infections and Hospitalizations among Persons Aged ≥16 Years, by Vaccination Status, Morb. Mortal. Wkly. Rep,
doi:10.15585/mmwr.mm7034e5Hall, Foulkes, Insalata, Kirwan, Saei et al., Protection against SARS-CoV-2 after COVID-19 Vaccination and Previous Infection, N. Engl. J. Med,
doi:10.1056/NEJMoa2118691Hanna, Dalvi, Sălăgean, Pop, Bordea et al., Understanding COVID-19 Pandemic: Molecular Mechanisms and Potential Therapeutic Strategies. An Evidence-Based Review, J. Inflamm. Res,
doi:10.2147/JIR.S282213Hariyanto, Intan, Hananto, Harapan, Kurniawan, Vitamin D supplementation and COVID-19 outcomes: A systematic review, meta-analysis and meta-regression, Rev. Med. Virol,
doi:10.1002/rmv.2269Jain, 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-zJeong, Vacanti, Disclaimer/Publisher's Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, Nutr. Metab,
doi:10.1186/s12986-020-00491-7Jolliffe, Vivaldi, Chambers, Cai, Li et al., Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial, Nutrients,
doi:10.3390/nu14183821Lamacchia, Mazzoni, Spinicci, Vanni, Salvati et al., Clinical and Immunological Features of SARS-CoV-2 Breakthrough Infections in Vaccinated Individuals Requiring Hospitalization, J. Clin. Immunol. 2022,
doi:10.1007/s10875-022-01325-2Lustig, Sapir, Regev-Yochay, Cohen, Fluss et al., COVID-19 vaccine and correlates of humoral immune responses and dynamics: A prospective, single-centre, longitudinal cohort study in health-care workers, Lancet Respir. Med,
doi:10.1016/S2213-2600(21)00220-4Mccartney, O'shea, Healy, Walsh, Griffin et al., The Causal Role of Vitamin D Deficiency in Worse COVID-19 Outcomes: Implications for Policy and Practice Development, Ir. Med. J
Pal, Banerjee, Bhadada, Shetty, Singh et al., Vitamin D supplementation and clinical outcomes in COVID-19: A systematic review and meta-analysis, J. Endocrinol. Investig,
doi:10.1007/s40618-021-01614-4Piec, Cook, Dervisevic, Fraser, Ruetten et al., Age and vitamin D affect the magnitude of the antibody response to the first dose of the SARS-CoV-2 BNT162b2 vaccine, Curr. Res. Transl. Med,
doi:10.1016/j.retram.2022.103344Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients,
doi:10.3390/nu12092757Shah, Varna, Sharma, Mavalankar, Does vitamin D supplementation reduce COVID-19 severity? a systematic review, QJM,
doi:10.1093/qjmed/hcac040Walsh, Mccartney, Laird, Mccarroll, Byrne et al., Understanding a Low Vitamin D State in the Context of COVID-19, Front. Pharmacol,
doi:10.3389/fphar.2022.835480Wolff, Nee, Hickey, Marschollek, Risk factors for COVID-19 severity and fatality: A structured literature review, Infection,
doi:10.1007/s15010-020-01509-1Zdrenghea, Makrinioti, Bagacean, Bush, Johnston et al., Vitamin D modulation of innate immune responses to respiratory viral infections, Rev. Med. Virol,
doi:10.1002/rmv.1909Zelini, Angelo, Cereda, Klersy, Sabrina et al., Association between Vitamin D Serum Levels and Immune Response to the BNT162b2 Vaccine for SARS-CoV-2, Biomedicines,
doi:10.3390/biomedicines10081993
