Vitamin D Deficiency Is Inversely Associated with COVID-19 Incidence and Disease Severity in Chinese People
Xia Luo, Qing Liao, Ying Shen, Huijun Li, Liming Cheng
doi:10.1093/jn/nxaa332.1
Background: Vitamin D might have beneficial potential in influencing the natural history of the coronavirus disease 2019 (COVID-19) due to its immunomodulatory and anti-inflammatory properties.
Objective: The aim was to investigate whether vitamin D deficiency is associated with COVID-19 incidence and disease severity in Chinese people.
Methods : In a cross-sectional study we retrospectively analyzed 335 COVID-19 patients (median: 56.0; IQR: 43.0-64.0 y) who were admitted to the Wuhan Tongji Hospital between 27 February and 21 March 2020. We also included an age-and sex-matched population of 560 individuals (median: 55; IQR: 49.0-60.0 y) who underwent the physical examination program. Their serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during the same period from 2018-2019. Serum 25(OH)D concentrations were measured for all COVID-19 patients on admission. Severity of COVID-19 was determined based on the level of respiratory involvement. A general linear model with adjustment for covariates was used to compare 25(OH)D concentrations between the COVID-19 and 2018-2019 control groups. Adjusted ORs with 95% CIs for associations between vitamin D status and COVID-19 severity were estimated via multivariable logistic regression. Results: In the general linear model adjusted for age, sex, comorbidities, and BMI, serum 25(OH)D concentrations were significantly lower among COVID-19 patients than the 2018-2019 controls [ln transformed values of 3.32 ± 0.04 vs. 3.46 ± 0.022 ln (nmol/L), P = 0.014]. Multivariable logistic regression showed that male sex (OR: 2.26; 95% CI: 1.06, 4.82), advanced age (≥65 y) (OR: 4.93; 95% CI: 1.44, 16.9), and vitamin D deficiency (<30 nmol/L) (OR: 2.72; 95% CI: 1.23, 6.01) were significantly associated with COVID-19 severity (all P < 0.05). Conclusions: These findings suggested that vitamin D deficiency impacts COVID-19 hospitalization and severity in the Chinese population.
Fisher's exact test. 3 Information on BMI was available for 45 cases in the discharged group and 4 in the death group. 4 Including hypertension, diabetes, cardiovascular disease, cerebrovascular disease, chronic lung diseases, chronic kidney disease, and tumors. 5 Serum 25(OH)D concentrations <30 nmol/L. 6 Serum 25(OH)D concentrations ≥30 nmol/L.
References
Arnold, COVID-19-does this disease kill due to imbalance of the renin angiotensin system (RAS) caused by genetic and gender differences in the response to viral ACE 2 attack?, Heart Lung Circ
Aygun, Vitamin D can prevent COVID-19 infection-induced multiple organ damage, Naunyn Schmiedebergs Arch Pharmacol
Beard, Bearden, Striker, Vitamin D and the anti-viral state, J Clin Virol
D'avolio, Avataneo, Manca, Cusato, Nicolo et al., 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2, Nutrients
Garcia-Carrasco, Jimenez-Herrera, Galvez-Romero, Mendoza-Pinto, Mendez-Martinez et al., The anti-thrombotic effects of vitamin D and their possible relationship with antiphospholipid syndrome, Lupus
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients
Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab Syndr
Hoe, Nathanielsz, Toh, Spry, Marimla et al., Anti-inflammatory effects of vitamin D on human immune cells in the context of bacterial infection, Nutrients
Holick, Vitamin D deficiency, N Engl J Med
Hooper, Nápoles, Pérez-Stable, COVID-19 and racial/ethnic disparities, JAMA
Kara, Ekiz, Ricci, Kara, Chang et al., Scientific strabismus" or two related pandemics: coronavirus disease and vitamin D deficiency, Br J Nutr
Levey, Stevens, Schmid, Zhang, Castro Af 3rd et al., A new equation to estimate glomerular filtration rate, Ann Intern Med
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Meftahi, Jangravi, Sahraei, Bahari, The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging, Inflamm Res
Meltzer, Best, Zhang, Vokes, Arora et al., Association of vitamin D deficiency and treatment with COVID-19 incidence. medRxiv,
doi:10.1101/2020.05.08.20095893Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study, FEBS J
Nair, Maseeh, Vitamin D: the "sunshine" vitamin, J Pharmacol Pharmacother
Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D deficiency and outcome of COVID-19 patients, Nutrients
Rhodes, Subramanian, Laird, Kenny, 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
Schwalfenberg, A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency, Mol Nutr Food Res
Science, Maguire, Russell, Smieja, Walter et al., Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents, Infect Dis
Teymoori-Rad, Shokri, Salimi, Marashi, The interplay between vitamin D and viral infections, Rev Med Virol
Verdoia, Pergolini, Nardin, Rolla, Negro et al., Vitamin D levels and platelet reactivity in diabetic patients receiving dual antiplatelet therapy, Vasc Pharmacol
Wang, Li, Yin, Zhang, Olsen et al., Vitamin D and chronic diseases, Aging Dis
Watkins, Lemonovich, Salata, An update on the association of vitamin D deficiency with common infectious diseases, Can J Physiol Pharmacol
Weiss, Murdoch, Clinical course and mortality risk of severe COVID-19, Lancet North Am Ed
Wong, Chan, Chan, Tse, Chim et al., Adverse effects of vitamin D deficiency on outcomes of patients with chronic hepatitis B, Clin Gastroenterol Hepatol
Xu, Yang, Chen, Luo, Zhang et al., Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the reninangiotensin system, Mol Med Rep
Zhang, Wu, Sun, Vitamin D, vitamin D receptor, and tissue barriers, Tissue Barriers
DOI record:
{
"DOI": "10.1016/j.annonc.2020.06.007",
"ISSN": [
"0923-7534"
],
"URL": "http://dx.doi.org/10.1016/j.annonc.2020.06.007",
"alternative-id": [
"S092375342039894X"
],
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "COVID-19 in patients with lung cancer"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "Annals of Oncology"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.annonc.2020.06.007"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2020 European Society for Medical Oncology. Published by Elsevier Ltd."
}
],
"author": [
{
"affiliation": [],
"family": "Luo",
"given": "J.",
"sequence": "first"
},
{
"affiliation": [],
"family": "Rizvi",
"given": "H.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Preeshagul",
"given": "I.R.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Egger",
"given": "J.V.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hoyos",
"given": "D.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bandlamudi",
"given": "C.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "McCarthy",
"given": "C.G.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Falcon",
"given": "C.J.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Schoenfeld",
"given": "A.J.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Arbour",
"given": "K.C.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chaft",
"given": "J.E.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Daly",
"given": "R.M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Drilon",
"given": "A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Eng",
"given": "J.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Iqbal",
"given": "A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Lai",
"given": "W.V.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "B.T.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Lito",
"given": "P.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Namakydoust",
"given": "A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ng",
"given": "K.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Offin",
"given": "M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Paik",
"given": "P.K.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Riely",
"given": "G.J.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Rudin",
"given": "C.M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Yu",
"given": "H.A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zauderer",
"given": "M.G.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Donoghue",
"given": "M.T.A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Łuksza",
"given": "M.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Greenbaum",
"given": "B.D.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Kris",
"given": "M.G.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hellmann",
"given": "M.D.",
"sequence": "additional"
}
],
"container-title": "Annals of Oncology",
"container-title-short": "Annals of Oncology",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"annalsofoncology.org",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2020,
6,
17
]
],
"date-time": "2020-06-17T01:47:45Z",
"timestamp": 1592358465000
},
"deposited": {
"date-parts": [
[
2022,
11,
17
]
],
"date-time": "2022-11-17T19:11:06Z",
"timestamp": 1668712266000
},
"funder": [
{
"DOI": "10.13039/100000002",
"doi-asserted-by": "publisher",
"name": "National Institutes of Health"
},
{
"DOI": "10.13039/100001021",
"doi-asserted-by": "publisher",
"name": "Damon Runyon Cancer Research Foundation"
},
{
"DOI": "10.13039/100000054",
"doi-asserted-by": "publisher",
"name": "National Cancer Institute"
}
],
"indexed": {
"date-parts": [
[
2024,
4,
4
]
],
"date-time": "2024-04-04T23:11:28Z",
"timestamp": 1712272288775
},
"is-referenced-by-count": 186,
"issue": "10",
"issued": {
"date-parts": [
[
2020,
10
]
]
},
"journal-issue": {
"issue": "10",
"published-print": {
"date-parts": [
[
2020,
10
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
10,
1
]
],
"date-time": "2020-10-01T00:00:00Z",
"timestamp": 1601510400000
}
},
{
"URL": "http://www.elsevier.com/open-access/userlicense/1.0/",
"content-version": "vor",
"delay-in-days": 365,
"start": {
"date-parts": [
[
2021,
10,
1
]
],
"date-time": "2021-10-01T00:00:00Z",
"timestamp": 1633046400000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S092375342039894X?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S092375342039894X?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "1386-1396",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2020,
10
]
]
},
"published-print": {
"date-parts": [
[
2020,
10
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1158/2159-8290.CD-20-0422",
"article-title": "Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak",
"author": "Dai",
"doi-asserted-by": "crossref",
"first-page": "783",
"journal-title": "Cancer Discov",
"key": "10.1016/j.annonc.2020.06.007_bib1",
"volume": "10",
"year": "2020"
},
{
"DOI": "10.1200/JCO.2020.38.18_suppl.LBA111",
"article-title": "Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): impact of type of cancer therapy and COVID therapy on survival",
"author": "Horn",
"doi-asserted-by": "crossref",
"journal-title": "J Clin Oncol",
"key": "10.1016/j.annonc.2020.06.007_bib2",
"volume": "38",
"year": "2020"
},
{
"DOI": "10.1016/j.annonc.2020.03.296",
"article-title": "Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "894",
"journal-title": "Ann Oncol",
"key": "10.1016/j.annonc.2020.06.007_bib3",
"volume": "31",
"year": "2020"
},
{
"DOI": "10.1016/S1470-2045(20)30096-6",
"article-title": "Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China",
"author": "Liang",
"doi-asserted-by": "crossref",
"first-page": "335",
"journal-title": "Lancet Oncol",
"key": "10.1016/j.annonc.2020.06.007_bib4",
"volume": "21",
"year": "2020"
},
{
"DOI": "10.1158/2159-8290.CD-20-0596",
"article-title": "Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers",
"author": "Luo",
"doi-asserted-by": "crossref",
"journal-title": "Cancer Discov",
"key": "10.1016/j.annonc.2020.06.007_bib5",
"year": "2020"
},
{
"DOI": "10.1186/1471-2172-9-1",
"article-title": "HLA class I supertypes: a revised and updated classification",
"author": "Sidney",
"doi-asserted-by": "crossref",
"first-page": "1",
"journal-title": "BMC Immunol",
"key": "10.1016/j.annonc.2020.06.007_bib6",
"volume": "9",
"year": "2008"
},
{
"DOI": "10.1016/j.cell.2020.05.015",
"article-title": "Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals",
"author": "Grifoni",
"doi-asserted-by": "crossref",
"issue": "7",
"journal-title": "Cell",
"key": "10.1016/j.annonc.2020.06.007_bib7",
"volume": "181",
"year": "2020"
},
{
"DOI": "10.1158/2159-8290.CD-20-0516",
"article-title": "Case fatality rate of cancer patients with COVID-19 in a New York Hospital System",
"author": "Mehta",
"doi-asserted-by": "crossref",
"journal-title": "Cancer Discov",
"key": "10.1016/j.annonc.2020.06.007_bib8",
"year": "2020"
},
{
"DOI": "10.1038/s41571-020-0362-6",
"article-title": "Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic",
"author": "Hanna",
"doi-asserted-by": "crossref",
"first-page": "268",
"journal-title": "Nat Rev Clin Oncol",
"key": "10.1016/j.annonc.2020.06.007_bib9",
"volume": "17",
"year": "2020"
},
{
"DOI": "10.1001/jama.2020.6775",
"article-title": "Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area",
"author": "Richardson",
"doi-asserted-by": "crossref",
"first-page": "2052",
"journal-title": "JAMA",
"key": "10.1016/j.annonc.2020.06.007_bib10",
"volume": "323",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)31189-2",
"article-title": "Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study",
"author": "Cummings",
"doi-asserted-by": "crossref",
"first-page": "1763",
"journal-title": "Lancet",
"key": "10.1016/j.annonc.2020.06.007_bib11",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1136/bmj.m1923",
"article-title": "Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study",
"author": "Lewnard",
"doi-asserted-by": "crossref",
"first-page": "m1923",
"journal-title": "BMJ",
"key": "10.1016/j.annonc.2020.06.007_bib12",
"volume": "369",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2004500",
"article-title": "Covid-19 in critically ill patients in the Seattle Region - case series",
"author": "Bhatraju",
"doi-asserted-by": "crossref",
"first-page": "2012",
"journal-title": "N Engl J Med",
"key": "10.1016/j.annonc.2020.06.007_bib13",
"volume": "382",
"year": "2020"
},
{
"DOI": "10.1056/NEJMc2009316",
"article-title": "Universal screening for SARS-CoV-2 in women admitted for delivery",
"author": "Sutton",
"doi-asserted-by": "crossref",
"first-page": "2163",
"journal-title": "N Engl J Med",
"key": "10.1016/j.annonc.2020.06.007_bib14",
"volume": "382",
"year": "2020"
},
{
"article-title": "Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments",
"author": "Barlesi",
"journal-title": "Presented at the AACR Virtual Annual Meeting",
"key": "10.1016/j.annonc.2020.06.007_bib15",
"year": "2020"
},
{
"DOI": "10.1038/s41591-020-0979-0",
"article-title": "Determinants of COVID-19 disease severity in patients with cancer",
"author": "Robilotti",
"doi-asserted-by": "crossref",
"journal-title": "Nat Med",
"key": "10.1016/j.annonc.2020.06.007_bib16",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)31187-9",
"article-title": "Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study",
"author": "Kuderer",
"doi-asserted-by": "crossref",
"first-page": "1907",
"issue": "10241",
"journal-title": "Lancet",
"key": "10.1016/j.annonc.2020.06.007_bib17",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1016/j.healun.2020.03.012",
"article-title": "COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal",
"author": "Siddiqi",
"doi-asserted-by": "crossref",
"first-page": "405",
"journal-title": "J Heart Lung Transplant",
"key": "10.1016/j.annonc.2020.06.007_bib18",
"volume": "39",
"year": "2020"
},
{
"DOI": "10.1084/jem.20200678",
"article-title": "The many faces of the anti-COVID immune response",
"author": "Vardhana",
"doi-asserted-by": "crossref",
"first-page": "e20200678",
"journal-title": "J Exp Med",
"key": "10.1016/j.annonc.2020.06.007_bib19",
"volume": "217",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)31208-3",
"article-title": "Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial",
"author": "Zhu",
"doi-asserted-by": "crossref",
"first-page": "1845",
"journal-title": "Lancet",
"key": "10.1016/j.annonc.2020.06.007_bib20",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1016/j.ijid.2020.03.017",
"article-title": "Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis",
"author": "Yang",
"doi-asserted-by": "crossref",
"first-page": "91",
"journal-title": "Int J Infect Dis",
"key": "10.1016/j.annonc.2020.06.007_bib21",
"volume": "94",
"year": "2020"
},
{
"DOI": "10.1161/CIRCULATIONAHA.120.046941",
"article-title": "COVID-19 and cardiovascular disease",
"author": "Clerkin",
"doi-asserted-by": "crossref",
"first-page": "1648",
"journal-title": "Circulation",
"key": "10.1016/j.annonc.2020.06.007_bib22",
"volume": "141",
"year": "2020"
},
{
"DOI": "10.1136/bmj.m1985",
"article-title": "Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study",
"author": "Docherty",
"doi-asserted-by": "crossref",
"first-page": "m1985",
"journal-title": "BMJ",
"key": "10.1016/j.annonc.2020.06.007_bib23",
"volume": "369",
"year": "2020"
},
{
"DOI": "10.1016/j.cell.2020.02.052",
"article-title": "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor",
"author": "Hoffmann",
"doi-asserted-by": "crossref",
"first-page": "271",
"journal-title": "Cell",
"key": "10.1016/j.annonc.2020.06.007_bib24",
"volume": "181",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2012410",
"article-title": "Observational study of hydroxychloroquine in hospitalized patients with Covid-19",
"author": "Geleris",
"doi-asserted-by": "crossref",
"first-page": "2411",
"issue": "25",
"journal-title": "N Engl J Med",
"key": "10.1016/j.annonc.2020.06.007_bib25",
"volume": "382",
"year": "2020"
},
{
"DOI": "10.1136/bmj.m1849",
"article-title": "Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial",
"author": "Tang",
"doi-asserted-by": "crossref",
"first-page": "m1849",
"journal-title": "BMJ",
"key": "10.1016/j.annonc.2020.06.007_bib26",
"volume": "369",
"year": "2020"
}
],
"reference-count": 26,
"references-count": 26,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S092375342039894X"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"Oncology",
"Hematology"
],
"subtitle": [],
"title": "COVID-19 in patients with lung cancer",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy",
"volume": "31"
}
