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/NEJMoa2119451
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
Argano, 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/ph16010130
Barrett, 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/nu14163252
Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms In Endocrinology: Vitamin D and COVID-19,
doi:10.1530/EJE-20-0665
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
Cashman, Dowling, Škrabáková, Gonzalez-Gross, Valtueña et al., Vitamin D deficiency in Europe: Pandemic?, Am. J. Clin. Nutr,
doi:10.3945/ajcn.115.120873
Chauss, 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/s41590-021-01080-3
Chen, 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-y
Chiodini, 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.2021.736665
Chiu, Tsai, Wu, Zheng, Yang et al., Putative Role of Vitamin D for COVID-19 Vaccination, Int. J. Mol. Sci,
doi:10.3390/ijms22168988
D'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.0268396
Dror, 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.0263069
Griffin, 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.mm7034e5
Hall, 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/NEJMoa2118691
Hanna, 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.S282213
Hariyanto, 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.2269
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, 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/s12986-020-00491-7
Jolliffe, 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/nu14183821
Lamacchia, 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/s10875-022-01325-2
Lustig, 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)00220-4
Mccartney, 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/s40618-021-01614-4
Piec, 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.2022.103344
Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients,
doi:10.3390/nu12092757
Shah, Varna, Sharma, Mavalankar, Does vitamin D supplementation reduce COVID-19 severity? a systematic review, QJM,
doi:10.1093/qjmed/hcac040
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
Wolff, Nee, Hickey, Marschollek, Risk factors for COVID-19 severity and fatality: A structured literature review, Infection,
doi:10.1007/s15010-020-01509-1
Zdrenghea, Makrinioti, Bagacean, Bush, Johnston et al., Vitamin D modulation of innate immune responses to respiratory viral infections, Rev. Med. Virol,
doi:10.1002/rmv.1909
Zelini, 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
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'DOI': '10.1056/NEJMoa2118691',
'article-title': 'Protection against SARS-CoV-2 after COVID-19 Vaccination and Previous '
'Infection',
'volume': '386',
'author': 'Hall',
'year': '2022',
'journal-title': 'N. Engl. J. Med.'},
{ 'key': 'ref_2',
'doi-asserted-by': 'crossref',
'first-page': '1532',
'DOI': '10.1056/NEJMoa2119451',
'article-title': 'COVID-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant',
'volume': '386',
'author': 'Andrews',
'year': '2022',
'journal-title': 'N. Engl. J. Med.'},
{ 'key': 'ref_3',
'doi-asserted-by': 'crossref',
'first-page': '898192',
'DOI': '10.3389/fimmu.2022.898192',
'article-title': 'Role of COVID-19 Vaccines in SARS-CoV-2 Variants',
'volume': '13',
'author': 'Zhou',
'year': '2022',
'journal-title': 'Front. Immunol.'},
{ 'key': 'ref_4',
'doi-asserted-by': 'crossref',
'unstructured': 'Chiu, S.K., Tsai, K.W., Wu, C.C., Zheng, C.M., Yang, C.H., Hu, W.C., '
'Hou, Y.C., Lu, K.C., and Chao, Y.C. (2021). Putative Role of Vitamin D '
'for COVID-19 Vaccination. Int. J. Mol. Sci., 22.',
'DOI': '10.3390/ijms22168988'},
{ 'key': 'ref_5',
'doi-asserted-by': 'crossref',
'unstructured': 'Jolliffe, D.A., Vivaldi, G., Chambers, E.S., Cai, W., Li, W., Faustini, '
'S.E., Gibbons, J.M., Pade, C., Coussens, A.K., and Richter, A.G. (2022). '
'Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy '
'or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised '
'Controlled Trial. Nutrients, 14.',
'DOI': '10.3390/nu14183821'},
{ 'key': 'ref_6',
'doi-asserted-by': 'crossref',
'unstructured': 'Zelini, P., d’Angelo, P., Cereda, E., Klersy, C., Sabrina, P., '
'Albertini, R., Grugnetti, G., Grugnetti, A.M., Marena, C., and Cutti, S. '
'(2022). Association between Vitamin D Serum Levels and Immune Response '
'to the BNT162b2 Vaccine for SARS-CoV-2. Biomedicines, 10.',
'DOI': '10.3390/biomedicines10081993'},
{ 'key': 'ref_7',
'doi-asserted-by': 'crossref',
'first-page': '103344',
'DOI': '10.1016/j.retram.2022.103344',
'article-title': 'Age and vitamin D affect the magnitude of the antibody response to the '
'first dose of the SARS-CoV-2 BNT162b2 vaccine',
'volume': '70',
'author': 'Piec',
'year': '2022',
'journal-title': 'Curr. Res. Transl. Med.'},
{ 'key': 'ref_8',
'doi-asserted-by': 'crossref',
'first-page': '999',
'DOI': '10.1016/S2213-2600(21)00220-4',
'article-title': 'BNT162b2 COVID-19 vaccine and correlates of humoral immune responses '
'and dynamics: A prospective, single-centre, longitudinal cohort study '
'in health-care workers',
'volume': '9',
'author': 'Lustig',
'year': '2021',
'journal-title': 'Lancet Respir. Med.'},
{ 'key': 'ref_9',
'doi-asserted-by': 'crossref',
'unstructured': 'Radujkovic, A., Hippchen, T., Tiwari-Heckler, S., Dreher, S., Boxberger, '
'M., and Merle, U. (2020). Vitamin D Deficiency and Outcome of COVID-19 '
'Patients. Nutrients, 12.',
'DOI': '10.3390/nu12092757'},
{ 'key': 'ref_10',
'doi-asserted-by': 'crossref',
'first-page': '1379',
'DOI': '10.1007/s10875-022-01325-2',
'article-title': 'Clinical and Immunological Features of SARS-CoV-2 Breakthrough '
'Infections in Vaccinated Individuals Requiring Hospitalization',
'volume': '42',
'author': 'Lamacchia',
'year': '2022',
'journal-title': 'J. Clin. Immunol.'},
{ 'key': 'ref_11',
'doi-asserted-by': 'crossref',
'first-page': '1170',
'DOI': '10.15585/mmwr.mm7034e5',
'article-title': 'SARS-CoV-2 Infections and Hospitalizations among Persons Aged ≥16 '
'Years, by Vaccination Status—Los Angeles County, California, May 1–July '
'25, 2021',
'volume': '70',
'author': 'Griffin',
'year': '2021',
'journal-title': 'Morb. Mortal. Wkly. Rep.'},
{ 'key': 'ref_12',
'doi-asserted-by': 'crossref',
'first-page': '875',
'DOI': '10.1016/j.mayocp.2021.01.001',
'article-title': 'Vitamin D Status Is Associated with In-Hospital Mortality and '
'Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients',
'volume': '96',
'author': 'Angelidi',
'year': '2021',
'journal-title': 'Mayo Clin. Proc.'},
{ 'key': 'ref_13',
'doi-asserted-by': 'crossref',
'unstructured': 'Dror, A.A., Morozov, N., Daoud, A., Namir, Y., Yakir, O., Shachar, Y., '
'Lifshitz, M., Segal, E., Fisher, L., and Mizrachi, M. (2022). '
'Pre-infection 25-hydroxyvitamin D3 levels and association with severity '
'of COVID-19 illness. PLoS ONE, 17.',
'DOI': '10.1371/journal.pone.0263069'},
{ 'key': 'ref_14',
'doi-asserted-by': 'crossref',
'unstructured': 'Barrett, R., Youssef, M., Shah, I., Ioana, J., Lawati, A.A., Bukhari, '
'A., Hegarty, S., Cormican, L.J., Judge, E., and Burke, C.M. (2022). '
'Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of '
'Unvaccinated Caucasian Adults. Nutrients, 14.',
'DOI': '10.3390/nu14163252'},
{ 'key': 'ref_15',
'doi-asserted-by': 'crossref',
'unstructured': 'Borsche, L., Glauner, B., and von Mendel, J. (2021). 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, 13.',
'DOI': '10.1101/2021.09.22.21263977'},
{ 'key': 'ref_16',
'doi-asserted-by': 'crossref',
'first-page': '665',
'DOI': '10.1093/qjmed/hcac040',
'article-title': 'Does vitamin D supplementation reduce COVID-19 severity? a systematic '
'review',
'volume': '115',
'author': 'Shah',
'year': '2022',
'journal-title': 'QJM'},
{ 'key': 'ref_17',
'first-page': 'e2269',
'article-title': 'Vitamin D supplementation and COVID-19 outcomes: A systematic review, '
'meta-analysis and meta-regression',
'volume': '32',
'author': 'Hariyanto',
'year': '2022',
'journal-title': 'Rev. Med. Virol.'},
{ 'key': 'ref_18',
'doi-asserted-by': 'crossref',
'first-page': '89',
'DOI': '10.1186/s12937-021-00744-y',
'article-title': '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',
'volume': '20',
'author': 'Chen',
'year': '2021',
'journal-title': 'Nutr. J.'},
{ 'key': 'ref_19',
'doi-asserted-by': 'crossref',
'first-page': 'R133',
'DOI': '10.1530/EJE-20-0665',
'article-title': 'Mechanisms In Endocrinology: Vitamin D and COVID-19',
'volume': '183',
'author': 'Bilezikian',
'year': '2020',
'journal-title': 'Eur. J. Endocrinol.'},
{ 'key': 'ref_20',
'doi-asserted-by': 'crossref',
'unstructured': 'D’Ecclesiis, O., Gavioli, C., Martinoli, C., Raimondi, S., Chiocca, S., '
'Miccolo, C., Bossi, P., Cortinovis, D., Chiaradonna, F., and Palorini, '
'R. (2022). Vitamin D and SARS-CoV2 infection, severity and mortality: A '
'systematic review and meta-analysis. PLoS ONE, 17.',
'DOI': '10.1371/journal.pone.0268396'},
{ 'key': 'ref_21',
'doi-asserted-by': 'crossref',
'first-page': '736665',
'DOI': '10.3389/fpubh.2021.736665',
'article-title': 'Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical '
'Outcomes',
'volume': '9',
'author': 'Chiodini',
'year': '2021',
'journal-title': 'Front. Public Health'},
{ 'key': 'ref_22',
'doi-asserted-by': 'crossref',
'unstructured': 'Argano, C., Mallaci Bocchio, R., Natoli, G., Scibetta, S., Lo Monaco, '
'M., and Corrao, S. (2023). 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, 16.',
'DOI': '10.3390/ph16010130'},
{ 'key': 'ref_23',
'doi-asserted-by': 'crossref',
'first-page': '53',
'DOI': '10.1007/s40618-021-01614-4',
'article-title': 'Vitamin D supplementation and clinical outcomes in COVID-19: A '
'systematic review and meta-analysis',
'volume': '45',
'author': 'Pal',
'year': '2022',
'journal-title': 'J. Endocrinol. Investig.'},
{ 'key': 'ref_24',
'doi-asserted-by': 'crossref',
'first-page': '1033',
'DOI': '10.3945/ajcn.115.120873',
'article-title': 'Vitamin D deficiency in Europe: Pandemic?',
'volume': '103',
'author': 'Cashman',
'year': '2016',
'journal-title': 'Am. J. Clin. Nutr.'},
{ 'key': 'ref_25',
'doi-asserted-by': 'crossref',
'first-page': 'e1909',
'DOI': '10.1002/rmv.1909',
'article-title': 'Vitamin D modulation of innate immune responses to respiratory viral '
'infections',
'volume': '27',
'author': 'Zdrenghea',
'year': '2017',
'journal-title': 'Rev. Med. Virol.'},
{ 'key': 'ref_26',
'doi-asserted-by': 'crossref',
'first-page': '13',
'DOI': '10.2147/JIR.S282213',
'article-title': 'Understanding COVID-19 Pandemic: Molecular Mechanisms and Potential '
'Therapeutic Strategies. An Evidence-Based Review',
'volume': '14',
'author': 'Hanna',
'year': '2021',
'journal-title': 'J. Inflamm. Res.'},
{ 'key': 'ref_27',
'doi-asserted-by': 'crossref',
'first-page': '62',
'DOI': '10.1038/s41590-021-01080-3',
'article-title': 'Autocrine vitamin D signaling switches off pro-inflammatory programs of '
'TH1 cells',
'volume': '23',
'author': 'Chauss',
'year': '2022',
'journal-title': 'Nat. Immunol.'},
{ 'key': 'ref_28',
'doi-asserted-by': 'crossref',
'first-page': '15',
'DOI': '10.1007/s15010-020-01509-1',
'article-title': 'Risk factors for COVID-19 severity and fatality: A structured '
'literature review',
'volume': '49',
'author': 'Wolff',
'year': '2021',
'journal-title': 'Infection'},
{ 'key': 'ref_29',
'doi-asserted-by': 'crossref',
'first-page': '881',
'DOI': '10.2310/JIM.0b013e31821b8755',
'article-title': 'Vitamin D and the immune system',
'volume': '59',
'author': 'Aranow',
'year': '2011',
'journal-title': 'J. Investig. Med.'},
{ 'key': 'ref_30',
'doi-asserted-by': 'crossref',
'first-page': '20191',
'DOI': '10.1038/s41598-020-77093-z',
'article-title': 'Analysis of vitamin D level among asymptomatic and critically ill '
'COVID-19 patients and its correlation with inflammatory markers',
'volume': '10',
'author': 'Jain',
'year': '2020',
'journal-title': 'Sci. Rep.'},
{ 'key': 'ref_31',
'doi-asserted-by': 'crossref',
'first-page': '835480',
'DOI': '10.3389/fphar.2022.835480',
'article-title': 'Understanding a Low Vitamin D State in the Context of COVID-19',
'volume': '13',
'author': 'Walsh',
'year': '2022',
'journal-title': 'Front. Pharmacol.'},
{ 'key': 'ref_32',
'first-page': 'P733',
'article-title': 'The Causal Role of Vitamin D Deficiency in Worse COVID-19 Outcomes: '
'Implications for Policy and Practice Development',
'volume': '116',
'author': 'McCartney',
'year': '2023',
'journal-title': 'Ir. Med. J.'},
{ 'key': 'ref_33',
'doi-asserted-by': 'crossref',
'first-page': '73',
'DOI': '10.1186/s12986-020-00491-7',
'article-title': 'Systemic vitamin intake impacting tissue proteomes',
'volume': '17',
'author': 'Jeong',
'year': '2020',
'journal-title': 'Nutr. Metab.'}],
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