Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients
Anna Regalia, Matteo Benedetti, Silvia Malvica, Carlo Alfieri, Mariarosaria Campise, Donata Cresseri, Maria Teresa Gandolfo, Federica Tripodi, Giuseppe Castellano, Piergiorgio Messa
Nutrients, doi:10.3390/nu14020317
Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12-26) vs. 23(17-31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5-0.7, p = 0.01). 25(OH)D was not significantly different between vs. 20(15-26) ng/mL, p = 0.19] and between D+ and D− [14(6-23) vs. 20(14-26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.
Informed Consent Statement: Given the observational and retrospective nature of the study, it was not necessary to obtain informed consent from patients. In any case, all of the data were collected digitally, analyzed, and reported in the results in a totally and anonymous manner.
Conflicts of Interest: The authors declare no conflict of interest.
References
Abdrabbo, Birch, Brandt, Cicigoi, Coffey et al., Vitamin D and COVID-19: A review on the role of vitamin D in preventing and reducing the severity of COVID-19 infection, Protein Sci,
doi:10.1002/pro.4190Akalin, Azzi, Bartash, Seethamraju, Parides et al., Covid-19 and Kidney Transplantation, N. Engl. J. Med,
doi:10.1056/NEJMc2011117Alfieri, Regalia, Zanoni, Vettoretti, Cozzolino et al., The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism, Blood Purif,
doi:10.1159/000492918Alfieri, Ruzhytska, Vettoretti, Caldiroli, Cozzolino et al., Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice, Nutrients,
doi:10.3390/nu11081918Bassatne, Basbous, Chakhtoura, El Zein, Rahme et al., The link between COVID-19 and Vitamin D (VIVID): A systematic review and meta-analysis, Metabolism,
doi:10.1016/j.metabol.2021.154753Benskin, 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.2020.00513Boulkrane, Ilina, Melchakov, Fedotova, Drago et al., COVID-19 Disease and Vitamin D: A Mini-Review, Front. Pharmacol,
doi:10.3389/fphar.2020.604579Brenner, Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths-Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action, Nutrients,
doi:10.3390/nu13020411Campi, Gennari, Merlotti, Mingiano, Frosali et al., Vitamin D and COVID-19 severity and related mortality: A prospective study in Italy, BMC Infect. Dis
Campise, Alfieri, Perego, Tamborini, Cresseri et al., COVID-19 Infection in Kidney Transplant Patients: An Italian One Year Single Centre Experience, Pathogens,
doi:10.3390/pathogens10080964Castillo, Costa, Barrios, Díaz, Miranda et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2020.105751Crafa, Cannarella, Condorelli, Mongioì, Barbagallo et al., Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis, EClinicalMedicine,
doi:10.1016/j.eclinm.2021.100967D'avolio, Avataneo, Manca, Cusato, De Nicolò et al., 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359De 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/aqaa252Flythe, Assimon, Tugman, Chang, Gupta et al., Characteristics and Outcomes of Individuals with Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States, Am. J. Kidney Dis,
doi:10.1053/j.ajkd.2020.09.003Greiller, Martineau, Modulation of the Immune Response to Respiratory Viruses by Vitamin D, Nutrients,
doi:10.3390/nu7064240Grove, Osokogu, Al-Khudairy, Mehrabian, Zanganeh et al., Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review, BMJ Open,
doi:10.1136/bmjopen-2020-043737Guan, Ni, Hu, Liang, Ou et al., Clinical Characteristics of Coronavirus Disease in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2002032Hernández, Nan, Fernandez-Ayala, García-Unzueta, Hernández-Hernández et al., Vitamin D Status in Hospitalized Patients with SARS-CoV-2
Jean, Souberbielle, Chazot, Vitamin D in Chronic Kidney Disease and Dialysis Patients, Nutrients,
doi:10.3390/nu9040328Jimenez, González-Parra, Riera, Rincón Bello, López-Herradón et al., Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics, Nutrients,
doi:10.3390/nu13082559Kaufman, Niles, Kroll, Bi, Holick, SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels, PLoS ONE,
doi:10.1371/journal.pone.0239252Kumar, Rathi, Haq, Wimalawansa, Sharma, Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19, Virus Res,
doi:10.1016/j.virusres.2020.198235Mercola, Grant, Wagner, Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity, Nutrients,
doi:10.3390/nu12113361Messa, Regalia, Alfieri, Nutritional Vitamin D in Renal Transplant Patients: Speculations and Reality, Nutrients,
doi:10.3390/nu9060550Oristrell, Oliva, Subirana, Casado, Domínguez et al., Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-Based Study, Biomedicines,
doi:10.3390/biomedicines9050509Ozturk, Turgutalp, Arici, Odabas, Altiparmak et al., Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: A nationwide analysis from Turkey, Nephrol. Dial. Transplant,
doi:10.1093/ndt/gfaa271Pecora, Persico, Argentiero, Neglia, Esposito, The Role of Micronutrients in Support of the Immune Response against Viral Infections, Nutrients,
doi:10.3390/nu12103198Quesada-Gomez, Bouillon, Is calcifediol better than cholecalciferol for vitamin D supplementation?, Osteoporos Int,
doi:10.1007/s00198-018-4520-yRadujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger et al., Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients,
doi:10.3390/nu12092757Raisi-Estabragh, Martineau, Curtis, Moon, Darling et al., Vitamin D and coronavirus disease 2019 (COVID-19): Rapid evidence review, Aging Clin. Exp. Res,
doi:10.1007/s40520-021-01894-zReynolds, Adhikari, Pulgarin, Troxel, Iturrate et al., Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2008975Santaolalla, Beckmann, Kibaru, Josephs, Van Hemelrijck et al., Association between Vitamin D and Novel SARS-CoV-2 Respiratory Dysfunction-A Scoping Review of Current Evidence and Its Implication for COVID-19 Pandemic, Front. Physiol,
doi:10.3389/fphys.2020.564387Stroehlein, Wallqvist, Iannizzi, Mikolajewska, Metzendorf et al., Vitamin D supplementation for the treatment of COVID-19: A living systematic review, Cochrane Database Syst. Rev
Teshome, Adane, Girma, Mekonnen, The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis, Front. Public Health,
doi:10.3389/fpubh.2021.624559Zelzer, Prüller, Curcic, Sloup, Holter et al., Vitamin D Metabolites and Clinical Outcome in Hospitalized COVID-19 Patients, Nutrients,
doi:10.3390/nu13072129DOI record:
{
"DOI": "10.3390/nu14020317",
"ISSN": [
"2072-6643"
],
"URL": "http://dx.doi.org/10.3390/nu14020317",
"abstract": "<jats:p>Background: Recently the protective role of 25-hydroxyvitamin D (25(OH)D) against viral infections has been hypothesized. We evaluated the association between vitamin D status and SARS-CoV-2 infection susceptibility and severity in a cohort of kidney transplanted patients (KTxp). Methods: A total of 61 KTxp with SARS-CoV-2 infection (COV+) were matched with 122 healthy KTxp controls (COV−). Main biochemical parameters at 1, 6, and 12 months before SARS-CoV-2 infection were recorded. Vitamin D status was considered as the mean of two 25(OH)D measures obtained 6 ± 2 months apart during the last year. The severity of SARS-CoV-2 infection was based on the need for hospitalization (HOSP+) and death (D+). Results: 25(OH)D levels were lower in COV+ than in controls [19(12–26) vs. 23(17–31) ng/mL, p = 0.01]. No differences among the other biochemical parameters were found. The SARS-CoV-2 infection discriminative power of 25(OH)D was evaluated by ROC-curve (AUC 0.61, 95% CI 0.5–0.7, p = 0.01). 25(OH)D was not significantly different between HOSP+ and HOSP− [17(8–25) vs. 20(15–26) ng/mL, p = 0.19] and between D+ and D− [14(6–23) vs. 20(14–26) ng/mL, p = 0.22] and had no significant correlation with disease length. Conclusions: During the year preceding the infection, 25(OH)D levels were lower in COV+ KTxp in comparison with controls matched for demographic features and comorbidities. No significant association between vitamin D status and SARS-CoV-2 infection related outcomes was found.</jats:p>",
"alternative-id": [
"nu14020317"
],
"author": [
{
"affiliation": [],
"family": "Regalia",
"given": "Anna",
"sequence": "first"
},
{
"affiliation": [],
"family": "Benedetti",
"given": "Matteo",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Malvica",
"given": "Silvia",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-3860-5219",
"affiliation": [],
"authenticated-orcid": false,
"family": "Alfieri",
"given": "Carlo",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Campise",
"given": "Mariarosaria",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Cresseri",
"given": "Donata",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gandolfo",
"given": "Maria Teresa",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Tripodi",
"given": "Federica",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Castellano",
"given": "Giuseppe",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Messa",
"given": "Piergiorgio",
"sequence": "additional"
}
],
"container-title": [
"Nutrients"
],
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2022,
1,
14
]
],
"date-time": "2022-01-14T08:14:03Z",
"timestamp": 1642148043000
},
"deposited": {
"date-parts": [
[
2022,
1,
18
]
],
"date-time": "2022-01-18T02:33:49Z",
"timestamp": 1642473229000
},
"indexed": {
"date-parts": [
[
2022,
1,
18
]
],
"date-time": "2022-01-18T06:00:41Z",
"timestamp": 1642485641245
},
"is-referenced-by-count": 0,
"issn-type": [
{
"type": "electronic",
"value": "2072-6643"
}
],
"issue": "2",
"issued": {
"date-parts": [
[
2022,
1,
13
]
]
},
"journal-issue": {
"issue": "2",
"published-online": {
"date-parts": [
[
2022,
1
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2022,
1,
13
]
],
"date-time": "2022-01-13T00:00:00Z",
"timestamp": 1642032000000
}
}
],
"link": [
{
"URL": "https://www.mdpi.com/2072-6643/14/2/317/pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1968",
"original-title": [],
"page": "317",
"prefix": "10.3390",
"published": {
"date-parts": [
[
2022,
1,
13
]
]
},
"published-online": {
"date-parts": [
[
2022,
1,
13
]
]
},
"publisher": "MDPI AG",
"reference": [
{
"DOI": "10.1056/NEJMoa2002032",
"doi-asserted-by": "publisher",
"key": "ref1"
},
{
"DOI": "10.1016/j.coph.2010.04.001",
"doi-asserted-by": "publisher",
"key": "ref2"
},
{
"DOI": "10.3390/nu7064240",
"doi-asserted-by": "publisher",
"key": "ref3"
},
{
"DOI": "10.1002/pro.4190",
"doi-asserted-by": "publisher",
"key": "ref4"
},
{
"DOI": "10.3390/nu11081918",
"doi-asserted-by": "publisher",
"key": "ref5"
},
{
"DOI": "10.3390/nu9060550",
"doi-asserted-by": "publisher",
"key": "ref6"
},
{
"DOI": "10.3390/pathogens10080964",
"doi-asserted-by": "publisher",
"key": "ref7"
},
{
"DOI": "10.1056/NEJMc2011117",
"doi-asserted-by": "publisher",
"key": "ref8"
},
{
"key": "ref9"
},
{
"DOI": "10.3390/nu12103198",
"doi-asserted-by": "publisher",
"key": "ref10"
},
{
"DOI": "10.1371/journal.ppat.1008874",
"doi-asserted-by": "publisher",
"key": "ref11"
},
{
"DOI": "10.1016/j.nut.2021.111356",
"doi-asserted-by": "publisher",
"key": "ref12"
},
{
"DOI": "10.3390/nu13020411",
"doi-asserted-by": "publisher",
"key": "ref13"
},
{
"DOI": "10.3389/fphar.2020.604579",
"doi-asserted-by": "publisher",
"key": "ref14"
},
{
"DOI": "10.3390/nu12113512",
"doi-asserted-by": "publisher",
"key": "ref15"
},
{
"DOI": "10.1016/j.virusres.2020.198235",
"doi-asserted-by": "publisher",
"key": "ref16"
},
{
"DOI": "10.3390/nu12051359",
"doi-asserted-by": "publisher",
"key": "ref17"
},
{
"DOI": "10.1371/journal.pone.0239252",
"doi-asserted-by": "publisher",
"key": "ref18"
},
{
"DOI": "10.3389/fpubh.2021.624559",
"doi-asserted-by": "publisher",
"key": "ref19"
},
{
"DOI": "10.3389/fphys.2020.564387",
"doi-asserted-by": "publisher",
"key": "ref20"
},
{
"DOI": "10.1016/j.metabol.2021.154753",
"doi-asserted-by": "publisher",
"key": "ref21"
},
{
"DOI": "10.1007/s40520-021-01894-z",
"doi-asserted-by": "publisher",
"key": "ref22"
},
{
"DOI": "10.1016/j.eclinm.2021.100967",
"doi-asserted-by": "publisher",
"key": "ref23"
},
{
"DOI": "10.1136/bmjopen-2020-043737",
"doi-asserted-by": "publisher",
"key": "ref24"
},
{
"DOI": "10.3390/nu12113361",
"doi-asserted-by": "publisher",
"key": "ref25"
},
{
"DOI": "10.3389/fpubh.2020.00513",
"doi-asserted-by": "publisher",
"key": "ref26"
},
{
"DOI": "10.1186/s12879-021-06281-7",
"doi-asserted-by": "publisher",
"key": "ref27"
},
{
"DOI": "10.3390/nu12092757",
"doi-asserted-by": "publisher",
"key": "ref28"
},
{
"DOI": "10.1093/ajcp/aqaa252",
"doi-asserted-by": "publisher",
"key": "ref29"
},
{
"DOI": "10.1016/j.jsbmb.2020.105751",
"doi-asserted-by": "publisher",
"key": "ref30"
},
{
"article-title": "Vitamin D supplementation for the treatment of COVID-19: A living systematic review",
"author": "Stroehlein",
"first-page": "CD015043",
"journal-title": "Cochrane Database Syst. Rev.",
"key": "ref31",
"volume": "2021",
"year": "2021"
},
{
"DOI": "10.1002/jbm4.10576",
"doi-asserted-by": "publisher",
"key": "ref32"
},
{
"DOI": "10.3390/nu9040328",
"doi-asserted-by": "publisher",
"key": "ref33"
},
{
"DOI": "10.1053/j.ajkd.2020.09.003",
"doi-asserted-by": "publisher",
"key": "ref34"
},
{
"DOI": "10.1093/ndt/gfaa271",
"doi-asserted-by": "publisher",
"key": "ref35"
},
{
"DOI": "10.3390/biomedicines9050509",
"doi-asserted-by": "publisher",
"key": "ref36"
},
{
"DOI": "10.3390/nu13082559",
"doi-asserted-by": "publisher",
"key": "ref37"
},
{
"DOI": "10.1016/j.cmet.2021.01.016",
"doi-asserted-by": "publisher",
"key": "ref38"
},
{
"DOI": "10.1056/NEJMoa2008975",
"doi-asserted-by": "publisher",
"key": "ref39"
},
{
"DOI": "10.1159/000492918",
"doi-asserted-by": "publisher",
"key": "ref40"
},
{
"DOI": "10.1007/s00198-018-4520-y",
"doi-asserted-by": "publisher",
"key": "ref41"
},
{
"DOI": "10.3390/nu13072129",
"doi-asserted-by": "publisher",
"key": "ref42"
},
{
"DOI": "10.1210/clinem/dgaa733",
"doi-asserted-by": "publisher",
"key": "ref43"
}
],
"reference-count": 43,
"references-count": 43,
"relation": {},
"score": 1,
"short-container-title": [
"Nutrients"
],
"short-title": [],
"source": "Crossref",
"subject": [
"Food Science",
"Nutrition and Dietetics"
],
"subtitle": [],
"title": [
"Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients"
],
"type": "journal-article",
"volume": "14"
}
