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The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality

Authors:
Cristian P Ilie at Norfolk and Norwich University Hospitals NHS Foundation Trust
Cristian P Ilie
Simina Stefanescu
Simina Stefanescu
Simina Stefanescu
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Lee Smith
Lee Smith
Lee Smith
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Abstract

Background/Aims: WHO declared SARS-Cov-2 a global pandemic. The aims of this paper are to assess if there is any association between mean levels of vitamin D in various countries and cases respectively mortality caused by COVID-19. Methods: We have identified the mean levels of vitamin D for 20 Europeans Countries for which we have also got the data regarding the morbidity and mortality caused by COVID-19. Results: The mean level of vitamin D (average 56mmol/L, STDEV 10.61) in each country was strongly associated with the number of cases/1M (mean 295.95, STDEV 298.73 p=0.004, respectively with the mortality/1M (mean 5.96, STDEV 15.13, p < 0.00001). Discussion: Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of population for COVID-19. Conclusions: We believe, that we can advise Vitamin D supplementation to protect against SARS-CoV2 infection.
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Preprint:Pleasenotethatthisarticlehasnotcompletedpeerreview.
TheroleofVitaminDinthepreventionofCoronavirus
Disease2019infectionandmortality
CURRENTSTATUS:POS TED
PetreCristianIlie
TheQueenElizabethHospitalFoundationTrust,King’sLynn
dr.cristianilie@gmail.comCorrespondingAuthor
SiminaStefanescu
UniversityofEastAnglia
LeeSmith
AngliaRuskinUniversity
DOI:
10.21203/rs.3.rs-21211/v1
SUBJECTAREAS
InfectiousDiseases
KEYWORDS
COVID-19,SARS-Cov2,Coronavirus,vitaminD,cholecalciferol,calcitriol
2
Abstract
Background/Aims:WHOdeclaredSARS-Cov-2aglobalpandemic.Theaimsofthispaperaretoassess
ifthereisanyassociationbetweenmeanlevelsofvitaminDinvariouscountriesandcases
respectivelymortalitycausedbyCOVID-19.
Methods:WehaveidentifiedthemeanlevelsofvitaminDfor20EuropeansCountriesforwhichwe
havealsogotthedataregardingthemorbidityandmortalitycausedbyCOVID-19.
Results:ThemeanlevelofvitaminD(average56mmol/L,STDEV10.61)ineachcountrywasstrongly
associatedwiththenumberofcases/1M(mean295.95,STDEV298.73p=0.004,respectivelywiththe
mortality/1M(mean5.96,STDEV15.13,p<0.00001).
Discussion:VitaminDlevelsareseverelylowintheagingpopulationespeciallyinSpain,Italyand
Switzerland.ThisisalsothemostvulnerablegroupofpopulationforCOVID-19.
Conclusions:Webelieve,thatwecanadviseVitaminDsupplementationtoprotectagainstSARS-CoV2
infection.
Background/aims
WHOdeclaredSARS-Cov–2aglobalpandemic.Littleisknownaboutthepotentialprotectivefactors.
PreviousstudiesidentifiedassociationsbetweenhigherlevelsofACE2andbettercoronavirusdisease
healthoutcomes.Inthelung,ACE2protectsagainstacutelunginjury[1].Calcitriol(1,25-
dihydroxyvitaminD3)exertspronouncedlyimpactsonACE2/Ang(1–7)/MasRaxiswithenhanced
expressionofACE2[2].
WehypothesizethatvitaminDmayplayaprotectiveroleforSARS-Cov2infections.
Theprimaryaimsofthisstudyaretoassessifthereisanyassociationbetweenthemeanlevelsof
vitaminDinvariouscountriesandthemortalitycausedbyCOVID–19.Thesecondaryaimwasto
identifyifthereisanyassociationbetweenthemeanvitaminDlevelsinvariouscountriesandthe
numberofcasesofCOVID–19.
MaterialsAndMethods
Totestthishypothesisandtolimitconfoundingbias(latitude,etc),wefocusedonEuropeancountries
only.WesearchedtheliteratureforthemeanlevelsofvitaminDineachcountry[3].Wesearched
thenumberofcasesofCOVID–19/1Mpopulationineachofthecountriesandmortalitycausedbythis
3
disease/1Mpopulation(20March,16.00GMT)(table1)[4].Statisticalanalyseswerecarriedout(t-test
calculator).
Results
WefoundverysignificantcorrelationbetweenthemeanvitaminDlevels(average56.79nmol/L,
STDEV10.61)andthenumberofcasesofCOVID–19/1Mpopulation(average259.95,STDEV298.732,
t-value=–3.03947;p-value=0.004274),andbetweenthemeanvitaminDlevelsandthenumberof
deathscausedbyCOVID–19/1M(Figure1)(average5.963936,STDEV15.13207,t-value=
12.29871;p-value<0.00001)(table1).
Discussion
Weacknowledgethatthiscross-sectionalanalysishaslimitations.Thenumberofcases/countryis
affectedbythenumberoftestsperformed.Webelievethatmortalityisabetteroutcometo
demonstratethepotentialprotectiveroleofvitaminD.
TheSenecastudyshowedameanserumvitaminDof26nmol/LinSpain,28 nmol/LinItalyand45 
nmol/LintheNordiccountries,inolderpeople[3].Severedeficiencyisdefinedasaserum25(OH)D
lowerthan30nmol/L[3].InSwitzerland,meanvitaminDlevelsare23(nmol/L)innursinghomesand
inItaly76%ofwomenover70yearsofagehavebeenfoundtohavecirculatinglevelsbelow
30nmol/L[3].ThesearecountrieswithhighnumberofcasesofCOVID–19andtheagingpeopleisthe
groupwiththehighestriskformorbidityandmortalitywithSARS-Cov2.
MartineauARetalconcludedinameta-analysisthatvitaminDsupplementationwassafeand
protectiveagainstacuterespiratorytractinfections.Theydescribedthatpatientswhoweresevere
vitaminDdeficientexperiencedthemostbenefit[5].
Inconclusion,wefoundsignificantrelationshipsbetweenvitaminDlevelsandthenumberCOVID–19
casesandespeciallythemortalitycausedbythisinfection.Themostvulnerablegroupofpopulation
forCOVID–19isalsotheonethathasthemostdeficitinVitaminD.
VitaminDhasalreadybeenshowntoprotectagainstacuterespiratoryinfectionsanditwasshownto
besafe.Webelieve,thatwecanadviseVitaminDsupplementationtoprotectagainstCOVID–19
infection.
Declarations
4
EthicalStatement
Thisstudyiscompliantwiththeethicalstandards.PetreCristianIlie,SiminaStefanescuandLee
Smithdonothaveanyconflictofinterests.Nosourceoffundingwasused.Consideringthedesignof
thestudynoinformedconsentwasnecessary.
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Table1
Notprovidedwiththisversionofthemanuscript.
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Figures
Figure1
MeanvitaminDlevels/countryversusthenumberofCOVID-19cases/1M
6
Figure2
MeanlevelsofvitaminDpercountryandcasesofCOVID-19mortality/1M
... Recent studies and meta analysis has reported that vitamin D deficiency is associated with COVID-19 mortality in Spain, Italy and Switzerland. [5][6][7] Hence with that background of literature the present brief review aimed to enlighten the associations between prevalence of Vitamin D deficiency and COVID-19 mortality rate in India. ...
... [30] It was observed that there was a significant positive correlation between COVID-19 mortality and prevalence of Vitamin D deficiency in other countries like Spain, Italy and Switzerland. [5] A role for vitamin D within the reaction to COVID-19 infection will be twofold, which might supports to produce antimicrobial peptides in the respiratory epithelium, hence making infection with the virus and development of COVID-19 signs less likely first. Secondly, might help to lessen the inflammatory reaction to infection with SARS-CoV-2. ...
... [31] Calcitriol exerts pronouncedly impacts on ACE2/Ang(1-7)/MasR (an endogenous orphan receptor, Mas) axis with enhanced expression of ACE2. [5,6] A R Martineau et al, in 2017 meta-analysis of individual patient data from 11,321 participants in 25 randomised controlled trials showed that vitamin D supplementation protected against acute respiratory tract infections and that patients with very low (<25 nmol/L) serum 25-hydroxyvitamin D concentrations (a marker of vitamin D status) gained the most benefit. [7] Recent studies were highlighted a crucial supportive role for vitamin D in immune cell function, particularly in modulating the inflammatory response to viral infection. ...
Vitamin-D deficiency as a predisposing cause for COVID-19 morbidities
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The Corona virus disease (COVID-19) mortality is increasing day to day due to the presence of co-morbidities and respiratory failure. The knowledge about the protective risk factors in associations with COVID-19 is still an assumption. Vitamin D protects against acute lung injury through enhanced expression Angiotensin-Converting Enzyme-2 and low levels were associated with upper respiratory tract infections. The increase in COVID-19 mortality rates is due to microvascular thrombosis which leads to respiratory failure and death. Previous literature showed that the protective role of Vitamin D on COVID-19 in various countries, but in a country like India the association with Vitamin D deficiency and COVID-19 mortality rate yet to be ruled out. Hence present review aimed to derive the association between COVID-19 mortality and deficiency of Vitamin D in India. The present brief review enlightened the positive association of vitamin-D deficiency with COVID-19 mortality.
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... A slightly higher correlation, as it should be, is present between T and D s . Note that our results are in agreement with the fact that increased vitamin D levels have been proposed to have a protective effect against COVID-19 [29][30][31]. Figure 16 ...
... This is quite interesting, since it may open avenues for research on protective factors and health policies. It is quite possible that high Vitamin D helps the immune response to COVID-19 [29][30][31]. Note, however, that this finding ...
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We analyze risk factors correlated with the initial transmission growth rate of the recent COVID-19 pandemic in different countries. The number of cases follows in its early stages an almost exponential expansion; we chose as a starting point in each country the first day di with 30 cases and we fitted for 12 days, capturing thus the early exponential growth. We looked then for linear correlations of the exponents α with other variables, for a sample of 126 countries. We find a positive correlation, i.e. faster spread of COVID-19, with high confidence level with the following variables, with respective p-value: low Temperature (4⋅10−7), high ratio of old vs. working-age people (3⋅10−6), life expectancy (8⋅10−6), number of international tourists (1⋅10−5), earlier epidemic starting date di (2⋅10−5), high level of physical contact in greeting habits (6⋅10−5), lung cancer prevalence (6⋅10−5), obesity in males (1⋅10−4), share of population in urban areas (2⋅10−4), cancer prevalence (3⋅10−4), alcohol consumption (0.0019), daily smoking prevalence (0.0036), and UV index (0.004, 73 countries). We also find a correlation with low Vitamin D serum levels (0.002−0.006), but on a smaller sample, ∼50 countries, to be confirmed on a larger sample. There is highly significant correlation also with blood types: positive correlation with types RH- (3⋅10−5) and A+ (3⋅10−3), negative correlation with B+ (2⋅10−4). We also find positive correlation with moderate confidence level (p-value of 0.02∼0.03) with: CO2/SO emissions, type-1 diabetes in children, low vaccination coverage for Tuberculosis (BCG). Several of the above variables are correlated with each other, and so they are likely to have common interpretations. We thus performed a Principal Component Analysis, to find the significant independent linear combinations of such variables. The variables with loadings of at least 0.3 on the significant PCA are: greeting habits, urbanization, epidemic starting date, number of international tourists, temperature, lung cancer, smoking, and obesity in males. We also analyzed the possible existence of a bias: countries with low GDP-per capita might have less intense testing, and we discuss correlation with the above variables.
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... Algunos países al norte de Europa presentan buenos niveles de vitamina D a pesar de su latitud, puesto que tienen un consumo elevado de vitamina D en sus alimentos y suplementos como es el caso de Suecia y Finlandia que presentan 73.5 y 67.7 nmol/L niveles séricos de vitamina D, respectivamente, con 68 y siete muertes por cada mil habitantes solamente. 23 Un estudio reciente en Indonesia asoció la mortalidad con la vitamina D, con una muestra de 780 pacientes confirmados con SARS-CoV-2, encontraron que la mayoría de los pacientes con vitamina D insuficiente murieron. Traduciendo esto a tener 10.12 veces más riesgo de morir con vitamina D deficiente; estos resultados son similares en nuestro estudio. ...
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View
... Epigenetic modifiers from natural resources (for example, from medicinal plants) would be the best medicine. In vitro data suggest that use of vitamin D and quercetin would ameliorate COVID-19 severity by inhibiting the expression of ACE2 and furin [192,193]. Curcumin and 8hydroxyquinolones may silence ACE2 and interferon genes by activation of DNMTs within viable clinical doses [194][195][196]. Among the notable drugs those can modulate DNA methylation and histone acetylation capacities are sulforaphane [197] and thymoquinone [198] that inhibit HDAC, lupeol and β-sitosterol from P. fotida plant extract that repress DNMTs, IL-6, IL1-β, TNF-α [199], and procyanidin B2 inhibits DNMTs [200]. ...
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... Randomized controlled trials and large population studies should be conducted to evaluate these recommendations [12].PetreCristianIlie et al,stated that Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of population for COVID-19 [13].F. M. Panfili et al.,had reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. ...
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... Vitamin D supplementation has been shown to be safe and effective against acute respiratory infections. Therefore, people with vitamin D deficiency during the pandemic should consume vitamin D supplements to maintain an optimal blood concentration [75,[94][95][96]. ...
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Full-text available
  • Sep 2023
Vitamin D merupakan prohormon yang memiliki fungsi utama mengatur keseimbangan kalsium tubuh. Sebagai imunoregulasi, vitamin D memiliki dua fungsi penting sebagai hormon sekosteroid pada regulasi hemostasis kalsium pada tubuh dan sebagai zat esensial organik yang sangat penting terhadap respons imun, Sebuah studi di Indonesia menunjukkan bahwa prevalensi defisiensi vitamin D sebesar 50% pada wanita berusia 45-55 tahun, kekurangan vitamin D dapat mengganggu sistem imun, meningkatkan risiko terjadinya rakitis pada anak atau lunaknya tulang sehingga mudah patah atau berubah bentuk pada orang dewasa. Kemudian juga dapat meningkatkan risiko tulang keropos (osteoporosis), penyakit autoimun, penyakit jantung dan pembuluh darah, diabetes, saluran pernapasan. Tinjauan literatur bertujuan sebagai kajian dan pustaka mutakhir mengenai ancaman defisiensi vitamin D di Indonesia yang menimbulkan kewaspadaan bagi penduduknya dan membahas juga peran vitamin D bagi kesehatannya. Desain menggunakan desain penelitian tinjauan literatur, Sumber data sekunder yang didapat berupa artikel yang relevan dengan topik dilakukan menggunakan database melalui Scopus, PubMed, Science Direct, CINAHL, ProQuest dan Garuda. hasil review menunjukkan beberapa manfaat terapi vitamin D terhadap daya tahan tubuh yaitu dapat memberikan kecukupan kadar vitamin D, memberikan kesehatan tulang terhidar dari osteoporosis, menstabilkan tekanan darah dan menurunkan apoptosis sel (khususnya pada pasien kanker). Serta pentingnya peran perawat dalam memberikan terapi untuk meningkatkan kualiatas hidup pasien yang memiliki defisiensi vitamin D adalah dengan edukasi mengenai pentingnya paparan matahari pada pukul 09.00-09.30 dan tambahan suplemen vitamin D dengan dosis antara 400-1000 UI/hari sesuai kebutuhan individu
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Prevention of COVID-19 with oral vitamin D supplemental therapy in essential healthcare teams (PROTECT): protocol for a multicentre, triple-blind, randomised, placebo-controlled trial
Article
Full-text available
  • May 2023
Introduction In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to reduce infection. Vitamin D insufficiency is highly prevalent in Canadians and worldwide. Vitamin D supplementation has been shown to significantly decrease the risk of respiratory infections. Whether this risk reduction would apply to COVID-19 infections remained to be determined. This study aimed to determine the impact of high-dose vitamin D supplementation on incidence of laboratory-confirmed COVID-19 infection rate and severity in HCWs working in high COVID incidence areas. Methods and analysis PROTECT was a triple-blind, placebo-controlled, parallel-group multicentre trial of vitamin D supplementation in HCWs. Participants were randomly allocated in a 1:1 ratio in variable block size to intervention (one oral loading dose of 100 000 IU vitamin D 3 +10 000 IU weekly vitamin D 3 ) or control (identical placebo loading dose+weekly placebo). The primary outcome was the incidence of laboratory-confirmed COVID-19 infection, documented by RT-qPCR on salivary (or nasopharyngeal) specimens obtained for screening or diagnostic purposes, as well as self-obtained salivary specimens and COVID-19 seroconversion at endpoint. Secondary outcomes included disease severity; duration of COVID-19-related symptoms; COVID-19 seroconversion documented at endpoint; duration of work absenteeism; duration of unemployment support; and adverse health events. The trial was terminated prematurely, due to recruitment difficulty. Ethics and dissemination This study involves human participants and was approved by the Research Ethics Board (REB) of the Centre hospitalier universitaire (CHU) Sainte-Justine serving as central committee for participating institutions (#MP-21-2021-3044). Participants provided written informed consent to participate in the study before taking part. Results are being disseminated to the medical community via national/international conferences and publications in peer-reviewed journals. Trial registration number https://clinicaltrials.gov/ct2/show/NCT04483635 .
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Severe COVID-19 patients have severe vitamin D deficiency in Northeast Mexico
Article
  • Feb 2022
  • NUTR HOSP
Objective: the association between vitamin D and COVID-19 severity is not consistent. We compared prevalences and analyzed the association between vitamin D deficiency and COVID-19 severity in Northeast Mexico. Methods: this was a cross-sectional study with individuals consecutively included at a referral diagnostic center during March-September 2020 (n = 181). Concurrently, every patient admitted to intensive care was also consecutively included (n = 116). Serum 25(OH)D < 20 ng/mL was considered vitamin D deficiency. Descriptive, ANOVA, and multivariate ordinal regression analyses were performed. Results: vitamin D deficiency prevalence was 63.8 % (95 % CI, 54.7, 72.0) in severe COVID-19; 25.6 % (95 % CI, 17.4, 36.0) in mild COVID-19; and 42.4 % (95 % CI, 33.2, 52.3) in non-diseased individuals. Vitamin D deficiency increased 5 times the odds of severe COVID-19 (95 % CI, 1.1, 24.3), independently of sex, age, body mass index, and inflammatory markers. Conclusions: this study is the first report of vitamin D deficiency in Northeast Mexico. Vitamin D deficiency was associated with COVID-19 severity.
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Previous vitamin D status and total cholesterol are associated with SARS-CoV-2 infection
Article
  • Aug 2021
  • CLIN CHIM ACTA
Background The relationship of vitamin D status and other biochemical parameters with the risk of SARS-CoV-2 infection remains inconclusive, especially in regions with high solar incidence. Therefore, we aimed to associate the 25-hydroxyvitamin D (25(OH)D) concentrations and lipid profile prior to the SARS-CoV-2 tests in a population from a sunny region in Brazil (5° S, 35° W). Methods This retrospective cohort study enrolled 1634 patients tested for SARS-CoV-2 of a private medical laboratory with 25(OH)D concentration and lipid profile measured ≥7 days before the date of the first SARS-CoV-2 RT-PCR test and were categorized according to 25(OH)D sufficiency (≥ 30 ng/ml) or insufficiency (< 30 ng/ml). Multiple logistic regression analyses were performed to assess risk factors associated with positive tests for SARS-CoV-2. Results Average serum 25(OH)D was 33.6 ng/ml. The vitamin D deficiency (< 20 ng/ml) reached only 2.6% of the participants. Multivariate analysis demonstrated that patients > 49 y with insufficient 25(OH)D (< 30 ng/ml) presented increased odds to test positive for SARS-CoV-2 (OR: 2.02, 95%CI: 1.15 to 3.55, P = 0.015). The same is observed among those with total cholesterol > 190 mg/dl (OR: 1.90, 95%CI: 1.10 to 3.28, P = 0.020). Conclusions Previous insufficient 25(OH)D (< 30 ng/ml) concentration and high total cholesterol were associated with SARS-CoV-2 infection among adults >48 y in the study population. Further studies should be conducted to confirm whether measurement of 25(OH)D and lipid profile could be useful to identify patients who are more susceptible to COVID-19.
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Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system
Article
Full-text available
  • Aug 2019
Hypertension is one of the major predisposing factors for neurodegenerative disease characterized with activated renin-angiotensin system (RAS) in both periphery and brain. Vitamin D (VitD) is recently recognized as a pleiotropic hormone with strong neuroprotective properties. While multiple lines of evidence suggest that VitD can act on RAS, the evidence concerning the crosstalk between VitD and RAS in the brain is limited. Therefore, this study aims to evaluate whether VitD can modulate brain RAS to trigger neuroprotective actions in the brain of spontaneously hypertensive rats (SHR). Our data showed that calcitriol treatment induced VDR expression and inhibited neural death in the prefrontal cortex of SHR. Sustained calcitriol administration also inhibited microglia M1 polarization, but enhanced M2 polarization, accompanied with decreased expression of proinflammatory cytokines. We then further explored the potential mechanisms and showed that SHR exhibited overactivated classical RAS with increased expression of angiotensin II (Ang II) receptor type 1 (AT1), angiotensin converting enzyme (ACE) and Ang II production, whereas the counteracting arm of traditional RAS, ACE2/Ang(1–7)/MasR, was impaired in the SHR brain. Calcitriol nonsignificantly suppressed AT1 and ACE but markedly reduced Ang II formation. Intriguingly, calcitriol exerted pronouncedly impact on ACE2/Ang(1–7)/MasR axis with enhanced expression of ACE2, MasR and Ang(1–7) generation. Meanwhile, calcitriol ameliorated the overactivation of NADPH-oxidase (Nox), the downstream of RAS, in SHR, and also mitigated oxidative stress. In microglial (BV2) cells, we further found that calcitriol induced ACE2 and MasR with no significant impact on ACE and AT1. In accordance, calcitriol also attenuated Ang II-induced Nox activation and ROS production, and shifted the microglia polarization from M1 to M2 phenotype. However, co-treatment with A779, a specific MasR antagonist, abrogated the antioxidant and neuroimmune modulating actions of VitD. These findings strongly indicate the involvement of ACE2/Ang(1–7)/MasR pathway in the neuroprotective mechanisms of VitD in the hypertensive brain. Keywords: Renin-angiotensin system, Vitamin D, Neuroinflammation, Oxidative stress, ACE2/Ang(1–7)/MasR axis
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MANAGEMENT OF ENDOCRINE DISEASE: Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency; a position statement of the European Calcified Tissue Society
Article
  • Feb 2019
Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l or 20 ng/ml), is common in Europe and the Middle East. It occurs in < 20 % of the population in Northern Europe, in 30-60% in Western, Southern and Eastern Europe and up to 80 % in Middle East countries. Severe deficiency (serum 25(OH)D < 30 nmol/l or 12 ng/ml) is found in > 10 % of Europeans. The ECTS advises that the measurement of serum 25(OH)D be standardized e.g. by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people, especially the institutionalized, and non-western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long term non-skeletal outcomes such as cancer.
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Angiotensin-converting enzyme 2 in lung diseases
  • Apr 2006
  • 271-276
  • K Kuka
  • Y Imai
  • J M Penninger
Kuka K, Imai Y, Penninger JM. Angiotensin-converting enzyme 2 in lung diseases. 2006 Jun;6(3):271-6. Epub 2006 Apr 3, available from: < 1.