This is a preprint. Preprints are preliminary reports that have not undergone peer review. They should not be considered conclusive, used to inform clinical practice, or referenced by the media as validated information.
Short Report
The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality
Petre Cristian Ilie
The Queen Elizabeth Hospital Foundation Trust, King’s Lynn
Corresponding Author
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Lay Summary
Lay Summary
created by Research Square
COVID-19, caused by the virus SARS-CoV-2, is a global pandemic, and no vaccines or curative treatments currently exist for the disease. Low levels of vitamin D, a nutrient found in fish, cheese, eggs, and many other foods, have been linked to an increased risk of various infectious diseases, including tuberculosis, HIV, fungal infections, and sepsis. This study evaluated whether blood vitamin D levels are associated with the number of COVID-19 cases and mortality. The researchers compared the mean levels of vitamin D in each country along with the number of cases of COVID-19 and COVID-19-related deaths per 1 million individuals. Analyses were limited to cases identified as of March 20, 2020 in European countries only. The results showed that low average vitamin D levels in a country are associated with a relatively high number of COVID-19 cases and deaths registered in that country. Because this study is a cross-sectional analysis, it does not evaluate the vitamin D levels specifically in infected individuals. Additionally, the number of SARS-CoV-2 tests performed remains limited in many areas. However, the data suggest that higher vitamin D levels may have a protective effect against COVID-19.
Lay Summary
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.
Keywords
COVID-19, SARS-Cov2, Corona virus, vitamin D, cholecalciferol, calcitriol
Figure 1
Figure 2
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.
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 disease/1M population (20March, 16.00GMT) (table 1)[4]. Statistical analyses were carried out (t-test calculator).
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).
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.
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.
- 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. https://www.sciencedirect.com/science/article/pii/S1471489206000579?via%3Dihub> [Accessed 20 March 2020]
- Cui C, Xu P, Li G, et al. 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. Redox Biol. 2019;26:101295. doi:10.1016/j.redox.2019.101295
- Lips, P., Cashman, K., Lamberg-Allardt, C., Bischoff-Ferrari, H., Obermayer-Pietsch, B., Bianchi, M., Stepan, J., El-Hajj Fuleihan, G., and Bouillon, R. (2019). 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. European Journal of Endocrinology 180, 4, P23-P54, available from: <https://doi.org/10.1530/EJE-18-0736> [Accessed 21 March 2020]
- https://www.worldometers.info/coronavirus/#countries. Accessed 20th March 17.1
- Martineau Adrian R, JolliffeDavid A,Hooper Richard L, Greenberg Lauren, Aloia John F, Bergman Peter et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017; 356 :i6583
Not provided with this version of the manuscript.
Nicola Jane Heady
ORCiDcommented on 09 April, 2020
This is an excellent piece of research. I also think that we should be looking at B12 deficiency also; particularly those that have subtle deficiency and undetected high levels of methylmalonic acid. This would also apply to the same demographics as above.
View 7 replies
rob martens
commented on 10 April, 2020
The picture becomes even clearer if you look within a country. The average amount of (UV) sunlight per year in, for example, northern Italy or the Wuhan district in China is clearly lower than in the rest of the country, which also points in the direction of the importance of vitamin D deficiency.
View 3 replies
James Larsen
replied on 01 May, 2020
Absolutely true that the platinum standard is a large intervention study. It is also true that a vaccine is 18 months or more away (Gates Foundation). Normalizing vit D to 60 ng/ml can do no harm (true, co-factors are an issue). Grassrootshealth.net study says that avoids catching flu by 43%. https://www.slideshare.net/James8981/flu-and-vit-d-230595341 https://www.slideshare.net/James8981/after-infection-with-the-coronavirus-vit-d https://www.slideshare.net/James8981/d-respiratory-tract https://www.slideshare.net/James8981/vit-d-by-race-age https://www.slideshare.net/James8981/vit-d-ards https://www.slideshare.net/James8981/vit-d-230595249
Wayne Cezair
replied on 05 May, 2020
Wuhan, China is covered in smog, Europe is getting out of winter. Most persons are covered from head to foot. The only place sunlight catches is the face which is now covered by a mask as it is most of the time in China. Australia and New Zealand are populated by persons who do not run form the sun and they are in their summer now. Virtually all homeless persons are asymptomatic although positive from being in the sun all day. Most persons work indoors in urban centers so likely have low D levels. It's pretty obvious and not sure why this is not being followed up on.
View 2 replies
matthew waite
replied on 05 May, 2020
There is also clear link between latitude north and mortality per million pop. Bringing up the levels in the population is likely to be highly cost effective. Finland supplement their food and have mortality rate 1/10th of the UK. Why are we not taking notice of this research?
View 2 replies
Martin Taylor
replied on 07 May, 2020
I must ask whether there may be a connection with the much higher rate of serious infection among people of colour in the UK. I would guess that they may find a higher level of vitamin D to be necessary for resistance to the worst effects of the virus. I acknowledge my limitations as a medical layman.
View 1 reply
MESFIN BEKO
replied on 24 May, 2020
Yes, people with black skin are more affected by Vit D deficiency. Bc the melanin in their skin prevent UV light to act on their skin rapidly. The need to stay under sun light for more time than whites.
Tina Logan
replied on 10 May, 2020
Is there any correlation would you say in the disproportionally high death rates in black, Asian and darker skinned people living in cold climates where they may be more likely deficient in Vitamin D?
View 1 reply
John Carlson
replied on 10 May, 2020
Yes absolutely as has been reported by Dr. John Campbell.
Nestor Eugênio Bassani
replied on 15 June, 2020
verdade sua colocação - conheço um mendigo há 15 anos e vive na rua , sem camisa, sujo, comendo restos e sempre com relativa saúde boa. Talvez seja esse sol abençõado que Deus deu a todos.
Joe Hooper
replied on 07 May, 2020
Yes looking into the area and weather also other deficiencies is good. China has an area known as the disease belt low in selenium.
View 1 reply
Tofazzal Hossain
replied on 12 May, 2020
What micronutrients fight against corona virus disease?
Rob
commented on 10 April, 2020
Good research. I have suspected this link for some time now. Other factors which are now recently becoming apparent are skin colour, smoking, pollution, weigh/obesity and genetics. It is interesting to note that Australia and New Zealand having good social distancing but also coming out of their summer have very few deaths.
View 1 reply
Michael
replied on 02 May, 2020
And also we are over-endowed with UV!
Arif Malik
commented on 11 April, 2020
Plz send the pdf form
Robert Brown
commented on 11 April, 2020
HI Congratulations - delighted your work, using an independent vitamin D data set, examining the question does vitamin D have a role In COVID-19, aka corona virus, concluded "The mean level of vitamin D (average 56mmol/L, STDEV 10.61) in each country was strongly associated with the number of cases/1M": which essentially comes to the same conclusion we did in the COVID-19 /vitamin d hypothesis paper below - posted 24th March - which in addition looks at intakes and deficiency - At that time there was not enough infection spread or data to usefully rely on deaths per M. It is surely time there was research looking at vitamin D levels, both in COVID-19 patients, and the wider population as a starting point. Thank you for your contribution. Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf Re: Preventing a covid-19 pandemic - COVID-19: Vitamin D deficiency; and, death rates; are both disproportionately higher in elderly Italians, Spanish, Swedish Somali, and African Americans? A connection? Research urgently required! https://www.bmj.com/content/368/bmj.m810/rr-46
View 1 reply
James Larsen
replied on 01 May, 2020
There is a tendency to see a vitamin as a lesser intervention than a drug. Yet, vit D can have a huge effect on outcomes: Look at POST-HOC ANALYSIS OF VITAMIN D STATUS AND REDUCED RISK OF PRETERM BIRTH IN TWO VITAMIN D PREGNANCY COHORTS COMPARED WITH SOUTH CAROLINA MARCH OF DIMES 2009-2011 RATES CL Wagner1, et al
Robert Brown
commented on 11 April, 2020
Hi Bob Martens Re vitamin D - logically given vit d has significant roles in respiratory function; it will factor in COVID-19 infection; thus infection, hospitalization, and death rates, will be impacted by time of year/ latitude / cloud cover / altitude / pollution etc. I graphed Spain and Italy by region against various COVID-19 metrics - results are interesting - but other factors are clearly shadowing and complicating COVID-19 outcomes.
Robert
commented on 11 April, 2020
HI It is excellent this paper confirms the results in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A posted on 24th March. https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and as also referred to in this BMJ letter https://www.bmj.com/content/368/bmj.m810/rr-46 (I struggle to understand why you moderated out my previous post pointing this out.)
Robert Brown
commented on 11 April, 2020
HI It is excellent this paper confirms the results in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A posted on 24th March. https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and as also referred to in this BMJ letter https://www.bmj.com/content/368/bmj.m810/rr-46 (I struggle to understand why you moderated out my 2 previous posts pointing this out - I have put in a formal complaint to Research Square - there are no reasonable grounds for this comment to be deleted.)
Robert Brown
commented on 11 April, 2020
HI I posted a comment to a preprint as below congratulating the authors and referring them to a previous paper on the same topic – and that their results independently confirmed the outcomes. The comment has twice been moderated out. Is suggest this is unacceptable and misplaced. I have raised the matter with our President Michael Crawford https://www.imperial.ac.uk/people/michael.crawford With many thanks Robert Brown
Robert Brown
commented on 11 April, 2020
Hi it is excellent this paper confirms the vitamin D levels may factor in COVID-19 aka corona virus mortality. It adds to evidence that the difference in mortality between Southern and Northern Europe may in part be due to higher intakes and supplementation in 'Northern Euorpe as we postualted in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality?' – An urgent call for research Brown R*, Sarkar A https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and further discussed in a letter to the BMJ. https://www.bmj.com/content/368/bmj.m810/rr-46 The likely importance of the pandemic of vitamin D deficiency in COVID-19 infection progression and mortality, is hugely under appreciated. Research is required as a matter of urgency. (Whoever keeps deleting my attempts to make this response, please desist - I am assured it is not the Authors)
Claude Lubicki
commented on 15 April, 2020
Hi, Thank you for this paper showing an apparent inverse relationship between Vitamin D serum levels and Covid-19 mortality in 20 EU countries. This identifies again the potential role of vitamin D mitigating this viral infection. There is only point which I am not sure to understand from your paper is about the ACE-2 receptor. My understanding is that VDR is a repressor of ACE-2 and not an activator. ref: G.V. Glinsky: Genomic-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic Regards, Claude
John G
commented on 15 April, 2020
Very good start on research. Obviously needs more research. The bottom chart is confusing as to what x and y are. titles for axis would help.
Steve Peat uk
commented on 19 April, 2020
The report is interesting, and my question why world health authorities do not test people Vitamin D levels in all age groups and ethnic groups. The governments need to test patients on people who suffering with the virus to see the relationship how patients needing oxygen have lower Vitamin D levels compared with mild cases. The next question to help treat patients could vitamin D injections given to patients who have started suffering from the virus could prevent them deteriorating to a level to need oxygen. The last question we have seen elderly people across the world include people over 100 survived the coronavirus compared to patients in the 50s, I.e, what bood chemistry these older people have to survive the coronavirus compared with other groups of people who have died with the virus. We need medical staff to carry out tests to investigate this report on patients include DNA how Vitamin D affects the body.
Louise
commented on 24 April, 2020
I have with much interest followed vitamin D studies and research for the past 6 years. Knowing that every one of our 70 trillion and more cells has a vitamin D receptor explains the importance of that hormone. Exciting.
Dr. David Bilstrom
commented on 28 April, 2020
I have been researching this also. Found a few studies - two are about patients on ventilators. 300,000 IU of vitamin D with an intramuscular injection; into the muscle. saw a 50% reduction in the death rates. Half the people were saved from dying with one dose of vitamin D. For these very sick people on ventilators, the average time was 10 days less for those. Effect of High-Dose Vitamin D on Duration of Mechanical Ventilation in ICU Patients https://pubmed.ncbi.nlm.nih.gov/31531088/ ************** High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. Journal of Clinical and Translational Endocrinology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939707/ ******************* Blood clotting an issue with Covid19 - Vitamin D as an anticoagulant https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069050/ ****************** Wrote a blog that includes video from me that summarizes these findings: https://bit.ly/Save-Lives-Injectible-VitaminD
View 2 replies
Eduardo Quinteros
replied on 02 May, 2020
But nothing was probed in those studies !
Michael G Crist
replied on 17 May, 2020
Consider the following 2015 [South] Korean study as well: "The Association Between Vitamin D Deficiency and Community-Acquired Pneumonia" https://journals.lww.com/md-journal/fulltext/2019/09200/the_association_between_vitamin_d_deficiency_and.65.aspx
Zhou Fang
commented on 01 May, 2020
This paper is a textbook example of correlation != causation. Absolutely terrible.
View 1 reply
Michael G Crist
replied on 17 May, 2020
Naturally... PRC would cast doubts on anything other than THEIR research & remedies!
Fraser Andrew
commented on 01 May, 2020
Given the strength of the association, the results from the other studies mentioned above, and the current emergency, surely one would not advise against Vitamin D supplementation, would one, Zhou Fang?
Linnéa Palme
commented on 02 May, 2020
I wrote this in Swedish on my facebook 24th of mars and same thoughts on my blogg april 22nd It´s on Covid-19- and three hormons- Vitamin D- Testosterone and Estrogen in this way I could se the age and groups early in February and also why not children got Covid-19. https://linneapalme.wordpress.com/2020/04/22/vem-drabbas-mest-och-varfor-covid-19/ and on april 25th I wrote https://linneapalme.wordpress.com/2020/04/25/den-nya-klimatfragan/
morris maizels
commented on 02 May, 2020
The table alleging a relationship between Vit D levels and mortality may have some statistical significance, but it appears that 2 outliers with low Vit D levels and mortality rate account for nearly of the relationship. As much as I would like to, I dont find this at all compelling evidence. Have I missed something?
VASSARAS ALEXANDROS
commented on 02 May, 2020
Excellent work ! We are working on a similar work ! and the findings are similar ! So the country with less deaths per million has also the most vitamin D levels in the population !
Haithum Ali
commented on 02 May, 2020
So I am totally convinced that vitamin D plays a crucial role in Cov19 defence, only time will tell, According to CDC, 33% of people hospitalised Cov19 in the US were African American who only constitute 13% of the population, by 45% were white people who make up 76% of the population. also, Somali immigrants living in Stockholm Sweden make up 40% of related Cov19 deaths, Sweden is a country that is at a northern latitude (57N' around 1900 sunlight a year and Somalia is 2N' 3200 sunlight a year) which increases vitamin D deficiency, this rate of hospitalisation is really high considering Somali’s make up 0.84% of Stockholm population. There is a very good reason why vitamin D have linked with cov19, there is data to suggest that vitamin D is protective against respiratory infection. Vitamin D an important role in the immune response and people with lower vitamin D may have a weaker immune response. People talk about that warm climate is good for killing the virus and cold is bad making the virus alive. but, our body temperature is 37 degrees Celsius and we know c19 can survive in that so if it's 37C or 40C outside, It would probably survive.
Gregory Joffe
commented on 04 May, 2020
Vitamin D deficiency in the majority of cases is caused by Magnesium deficiency, which is usually in the mentioned groups of the population. Thus recommendations for vitamin D should come together with recommendations for magnesium supplements.
Josef Dietl
commented on 04 May, 2020
Would you kindly label your graphs?
Peter Garvin
ORCiDcommented on 05 May, 2020
With all respect, this study can't be used neither to support nor reject the hypothesis. If this would have been a wriiten exam in epidemiology, I would have failed the students for the following reasons: 1) Data clearly suggests that is not appropriate to use t-test. As you all know, incidence rates are seldomly normally distributed. Having a STDEV that exceeds the mean is not a good sign, it indicates that the entire analysis is idependent on one or a few outliers. 2) Number of tested persons with positive result is not a good proxy for number of cases in the population. It has been clear from the start the different countries has applied different approaches regarding number of tests as well as which groups should be tested. (Not to mention the specificity and sensitivity issues). 3) Since the mortality rates vary highly with age, analyses should have been age standardized in some way. It is almost sad to see that the authors claim to minimize confounding without taking demographics into account. This could have been easily done, stratifying the material based on age groups and standardize for age specific vitamin D reference interval (or at least estimations of age specific intervals). 4) The correlation in Figure 2 on mortality implies that, given that the correlation is true, you could have a negative mortality rate. Clearly, linear fitting is not always ideal, and this could, I am afraid, be used as a school book example to illustrate that. Apart from the note on philosophy of science that a correlation cannot be "very significant" as stated, the coefficient seems to be highly depending on one single outlier. (Further, it seems that the different countries are not weighted in relation to population size, which supersizes the impact of small countries). I could go on, but I think my message is clear. I have no wish neither to support or reject the hypothesis on vitamin D. There is a need for carefully considered and planned analyses to increase our understanding. This paper does simply not meet the scientific standard needed to conclude that vitamin D supplementation should be used to protect against COVID–19 infection. It is not the design per se that limits the value (which by the way is ecolological rather than cross-sectional as stated), it is the amount of methodological flaws in the analyses.
View 1 reply
Wynn Quon
replied on 08 May, 2020
These are really good points. Thanks for this. Everyone wants so much to believe. The original authors should address these shortcomings pronto.
View 1 reply
Michael G Crist
replied on 17 May, 2020
How many will die unnecessarily within the next three months because of this delay?
stephen lee
commented on 07 May, 2020
Clearly many factors, e.g. skin colour and type of dress, affect winter Vitamin D levels in northern Europe. Income, or wealth, is another such variable, as very many of the richer Northern Europeans typically manage to relocate to somewhere considerably more sunny for at at least a couple of weeks in the winter, as anyone who has been to SE Asia, the Caribbean, or the Canary Islands In January will have noticed
Benjamin Layton
commented on 13 May, 2020
I've been looking at the data for a while as well, Vitamin D3 is going to play an important part in fortifying the aging populations and B12 will need to be examined as well due to the antimicrobial properties of cobalt and cobaltamine. The virus in general seems to be somewhat resistant to damage from sources of vitamin c, but oxidized vitamin c seems to still be an efficient way to transport reactive oxygen species into cells for their intended function. We need to gather data from a wide population and have their vitamin levels examined as well as a self report of how sever they felt their symptoms to be.
Dr Gary Barker
ORCiDcommented on 15 May, 2020
A really interesting study. Can the data underlying figs 1 and 2 be shared please? It would be helpful if they could be looked at by the wider community.
Lynne
commented on 15 May, 2020
Regarding Covid19 in African and Afro Caribbean communities, has it is anyone looked into the relevance of sickle cell trait? It is a mild version of sickle cell disease which many sufferers are unaware they have. It can, however, be very dangerous if the person becomes short of oxygen. I am not a scientist, just a concerned layperson but this seems very relevant to me and I do not know whether this has been looked into.
View 1 reply
Sharon
replied on 16 May, 2020
Hello I have also been wondering whether there's a link between the sickle cell trait and Covid outcomes.
View 1 reply
Patricia Jones
replied on 19 June, 2020
I have also been wonderung about sickle cell and thaleassemia. Has anybody look at at anti phospholiped auto immune disorder ?
William J. Kelleher
commented on 16 May, 2020
You have a typo in the extract... you use mmol/L instead of the proper nmol/L. If someone's vitamin d level were that high, they'd be dead.
View 1 reply
William J. Kelleher
replied on 16 May, 2020
*abstract
Zim Laboratories
commented on 19 May, 2020
According to a study, Vitamin D3 has the potential to help the human body fight against COVID-19. It reduces the occurrence of fewer upper respiratory tract infections including influenza. In several scientific studies, it has also been reported that Vitamin D3 supplement is beneficial in reducing the risks of Influenza, Dengue, hepatitis C, Herpes, HIV, RSV, etc.
Meg
commented on 22 May, 2020
I had a very severe and unusual flu 4 years past onset was fever, a dry hacking cough i also had a sudden loss of sensation on one side of my body, crazy dreams or hallucinations at home 3 days with the fever then i happened to have a rapid decline ending up hospitalized in a very small rural hospital with very limited resources I couldnt breath well, I was dehydrated from fever I.V started, was found to have severely low salts from what they thought was overhydration, my BP was terribly low 80/43 with fast pulse, it felt as though something was constantly squeezing my throat and as though someone sat on my chest, the coughing was wretched, my vision was affected and blurred, no swabs of any sort were taken as they didn't have any, clarithromycin type drug was given by I.V. as well as prednisone to open my airways through I.V. my windpipe felt opened in a matter of half hour or so, my blood panel showed severely low VITIMIN D it took me months to recover, they released me to my mother my mom feared i would die if they kept me!, the sent me home with zpac, prednisone, and vitimin D and calcium intake instructions. My Mother kept me with her for 2 months and nursed me back to health using B12, 4000 ui of Vitimin D which I needed to take for a year, i now take a daily dose of 2000 ui, my husband is a smoker and ive had him on 4000 ui per day since covid began in Canada here. i thought i would share my story that you all may find my story interesting as i must say i thought i was going to die from that respiratory flu i had, and perhaps if i wasn't deficient in Vitimin D maybe i would have gotten that sick I almost died at the age of 42. Good luck with your research I do believe you are on to something!
Burton C Butterfield
commented on 27 May, 2020
is there enough data which compares the mortality rate in patients who have normal vitamin D before concluding a positive correlation to the rate in those northern European countries
John Sloss
commented on 10 July, 2020
I am interested in the fact that bats from whom many researchers believe the virus originated are short of vitamin D. This is not surprising as they are nocturnal and many roost in caves. Although I am a retired Consultant in Microbiology FRCPath and my knowledge of immunology is somewhat limited I believe there is some published evidence of vitamin D and T cell function. It therefore seems to make sense to supplement high latitude human populations with vitamin D a relatively safe cheap and available measure. What of course would be interesting would be to measure vitamin D levels in patients with poor outcomes in corona virus
sceptic
commented on 15 July, 2020
We should combine it also with regional pollution levels https://www.dutchnews.nl/news/2020/07/farm-and-vehicle-emissions-made-coronavirus-worse-in-south-study/
Pg
commented on 01 August, 2020
Corona: prevent, vitamin d? No!
Ntombikayise Precious Bhengu
commented on 08 August, 2020
Excellent research! Does this mean, if people took supplements of vitamin D, in addition to wearing protective gear, social distancing, sanitizing and washing hands every now and then, it would reduce their chances of people getting infected with COVI-19?
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Short Report
The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality
Petre Cristian Ilie
The Queen Elizabeth Hospital Foundation Trust, King’s Lynn
Corresponding Author
Badges
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This manuscript passed our Prescreen assessment
Complete author information
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CURRENT STATUS: Posted
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Posted 08 Apr, 2020
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On 06 May, 2020
Community comments: 68
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Comments: 68
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Lay Summary
Lay Summary
created by Research Square
COVID-19, caused by the virus SARS-CoV-2, is a global pandemic, and no vaccines or curative treatments currently exist for the disease. Low levels of vitamin D, a nutrient found in fish, cheese, eggs, and many other foods, have been linked to an increased risk of various infectious diseases, including tuberculosis, HIV, fungal infections, and sepsis. This study evaluated whether blood vitamin D levels are associated with the number of COVID-19 cases and mortality. The researchers compared the mean levels of vitamin D in each country along with the number of cases of COVID-19 and COVID-19-related deaths per 1 million individuals. Analyses were limited to cases identified as of March 20, 2020 in European countries only. The results showed that low average vitamin D levels in a country are associated with a relatively high number of COVID-19 cases and deaths registered in that country. Because this study is a cross-sectional analysis, it does not evaluate the vitamin D levels specifically in infected individuals. Additionally, the number of SARS-CoV-2 tests performed remains limited in many areas. However, the data suggest that higher vitamin D levels may have a protective effect against COVID-19.
Lay Summary
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.
Figure 1
Figure 2
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.
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 disease/1M population (20March, 16.00GMT) (table 1)[4]. Statistical analyses were carried out (t-test calculator).
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).
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.
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.
- 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. https://www.sciencedirect.com/science/article/pii/S1471489206000579?via%3Dihub> [Accessed 20 March 2020]
- Cui C, Xu P, Li G, et al. 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. Redox Biol. 2019;26:101295. doi:10.1016/j.redox.2019.101295
- Lips, P., Cashman, K., Lamberg-Allardt, C., Bischoff-Ferrari, H., Obermayer-Pietsch, B., Bianchi, M., Stepan, J., El-Hajj Fuleihan, G., and Bouillon, R. (2019). 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. European Journal of Endocrinology 180, 4, P23-P54, available from: <https://doi.org/10.1530/EJE-18-0736> [Accessed 21 March 2020]
- https://www.worldometers.info/coronavirus/#countries. Accessed 20th March 17.1
- Martineau Adrian R, JolliffeDavid A,Hooper Richard L, Greenberg Lauren, Aloia John F, Bergman Peter et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017; 356 :i6583
Not provided with this version of the manuscript.
Nicola Jane Heady
ORCiDcommented on 09 April, 2020
This is an excellent piece of research. I also think that we should be looking at B12 deficiency also; particularly those that have subtle deficiency and undetected high levels of methylmalonic acid. This would also apply to the same demographics as above.
View 7 replies
Philip Barr, MD
replied on 07 May, 2020
Thank you for publishing this helpful data. While the physiology of Vitamin D-2 and D-3 has been known for decades in promoting both innate and adaptive immunity , specific research on COVID-19 has been lacking. Advising physician support in testing levels to reach optimal, as you suggest, is well-intended. Anywhere that physician services are hard to schedule, as during this stay-at-home pandemic, would allow for a safe generic recommendation of 2-4,000 IU per day orally until a level can be measured. Again, thank you for this altruistic much needed service! Philip Barr, MD USA
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Michael G Crist
replied on 17 May, 2020
Vitamin D2 should be excluded from consideration at this point. Multiple studies have indicated that it is a considerably weaker choice of Vitamin D supplementation. Discussion should be limited to Vitamin D3 only, specifically with regard to COVID-19.
Courtney
replied on 07 May, 2020
You make a really good point, but I feel like dietary lifestyles should be looked at as well. Examples: Vegetarians and vegans don’t eat enough vitamins, nutrients, and/or minerals their body needs. And what a lot of people lack whether they eat meat or not is iron so that shouldn’t definitely be looked into and researched as well. Apart from vitamin D, the vitamins/minerals that both vegetarians typically need: Iron, Zinc, and Magnesium. Yes, while we need other vitamins and minerals, the above minerals are the ones we need the most over the other minerals. Also, with Vitamin B6 I think you have to be careful with that where it is necessary but if you take too much, it’s not good for the body.
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Mark
replied on 14 May, 2020
Courtney, do you have significant clinical data to show what you're saying about vegetarians and vegans RE vitamins? In fact, I'd be even more interested to see something significant that shows specific deficiencies vs omnivorous diets. Otherwise, that's quite the claim you're making there.
George
replied on 15 May, 2020
I would also agree about looking into other vitamins and the overall impact of diet. At the same time, I'd raise the same questions as below about a source of the claims towards vegetarian and vegan diets as the literature seems to imply a different picture: Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967195/ From the study's conclusion: 'In conclusion, results concerning body weight, nutritional intake, nutritional quality and quantity are in line with the literature on restricted and prudent diets versus unrestricted omnivorous diet. The use of indexing systems, estimating the overall diet quality based on different aspects of healthful dietary models indicated consistently the vegan diet as the most healthy one.'
Linda
replied on 16 May, 2020
Vitamin B6, like other B vitamins, is water soluble. Any excess is easily excreted, and not likely to cause problems.
Caroline
replied on 27 May, 2020
Do you think that individuals that have genetic problems with their red blood cells like stomatocytosis can be more sick in covid-19 because of the lack of b12 that works normal in others without stomatocytosis.
Mrs Rebecca Bradshaw
replied on 09 June, 2020
Hi, I think I had covid mildly last year lasting for two months. I had a blood test that picked up that my vitamin D was not just low but through the floor. I read an article in the guardian saying that someone else suffering from covid had a very low vitamin d deficiency after catching it. What if covid-19 causes the body to reduce its vitamin d level? This all people that catch it appear to have a low vitamin d level?
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Jan Claessens
replied on 11 June, 2020
Which Corona strain where you infected with and when was de bloedtest taken? If you stayed inside for a long time, very low D is quite normal...
replied on 26 June, 2020
With higher B12 You also have more NK s that will help with covid 19 . I take 2500 IE Vitamine D abd once a year i make a B 12 Cure.
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replied on 11 July, 2020
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replied on 31 July, 2020
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rob martens
commented on 10 April, 2020
The picture becomes even clearer if you look within a country. The average amount of (UV) sunlight per year in, for example, northern Italy or the Wuhan district in China is clearly lower than in the rest of the country, which also points in the direction of the importance of vitamin D deficiency.
View 3 replies
James Larsen
replied on 01 May, 2020
Absolutely true that the platinum standard is a large intervention study. It is also true that a vaccine is 18 months or more away (Gates Foundation). Normalizing vit D to 60 ng/ml can do no harm (true, co-factors are an issue). Grassrootshealth.net study says that avoids catching flu by 43%. https://www.slideshare.net/James8981/flu-and-vit-d-230595341 https://www.slideshare.net/James8981/after-infection-with-the-coronavirus-vit-d https://www.slideshare.net/James8981/d-respiratory-tract https://www.slideshare.net/James8981/vit-d-by-race-age https://www.slideshare.net/James8981/vit-d-ards https://www.slideshare.net/James8981/vit-d-230595249
Wayne Cezair
replied on 05 May, 2020
Wuhan, China is covered in smog, Europe is getting out of winter. Most persons are covered from head to foot. The only place sunlight catches is the face which is now covered by a mask as it is most of the time in China. Australia and New Zealand are populated by persons who do not run form the sun and they are in their summer now. Virtually all homeless persons are asymptomatic although positive from being in the sun all day. Most persons work indoors in urban centers so likely have low D levels. It's pretty obvious and not sure why this is not being followed up on.
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matthew waite
replied on 05 May, 2020
There is also clear link between latitude north and mortality per million pop. Bringing up the levels in the population is likely to be highly cost effective. Finland supplement their food and have mortality rate 1/10th of the UK. Why are we not taking notice of this research?
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Martin Taylor
replied on 07 May, 2020
I must ask whether there may be a connection with the much higher rate of serious infection among people of colour in the UK. I would guess that they may find a higher level of vitamin D to be necessary for resistance to the worst effects of the virus. I acknowledge my limitations as a medical layman.
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MESFIN BEKO
replied on 24 May, 2020
Yes, people with black skin are more affected by Vit D deficiency. Bc the melanin in their skin prevent UV light to act on their skin rapidly. The need to stay under sun light for more time than whites.
Tina Logan
replied on 10 May, 2020
Is there any correlation would you say in the disproportionally high death rates in black, Asian and darker skinned people living in cold climates where they may be more likely deficient in Vitamin D?
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John Carlson
replied on 10 May, 2020
Yes absolutely as has been reported by Dr. John Campbell.
Nestor Eugênio Bassani
replied on 15 June, 2020
verdade sua colocação - conheço um mendigo há 15 anos e vive na rua , sem camisa, sujo, comendo restos e sempre com relativa saúde boa. Talvez seja esse sol abençõado que Deus deu a todos.
Joe Hooper
replied on 07 May, 2020
Yes looking into the area and weather also other deficiencies is good. China has an area known as the disease belt low in selenium.
View 1 reply
Tofazzal Hossain
replied on 12 May, 2020
What micronutrients fight against corona virus disease?
Rob
commented on 10 April, 2020
Good research. I have suspected this link for some time now. Other factors which are now recently becoming apparent are skin colour, smoking, pollution, weigh/obesity and genetics. It is interesting to note that Australia and New Zealand having good social distancing but also coming out of their summer have very few deaths.
View 1 reply
Michael
replied on 02 May, 2020
And also we are over-endowed with UV!
Arif Malik
commented on 11 April, 2020
Plz send the pdf form
Robert Brown
commented on 11 April, 2020
HI Congratulations - delighted your work, using an independent vitamin D data set, examining the question does vitamin D have a role In COVID-19, aka corona virus, concluded "The mean level of vitamin D (average 56mmol/L, STDEV 10.61) in each country was strongly associated with the number of cases/1M": which essentially comes to the same conclusion we did in the COVID-19 /vitamin d hypothesis paper below - posted 24th March - which in addition looks at intakes and deficiency - At that time there was not enough infection spread or data to usefully rely on deaths per M. It is surely time there was research looking at vitamin D levels, both in COVID-19 patients, and the wider population as a starting point. Thank you for your contribution. Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf Re: Preventing a covid-19 pandemic - COVID-19: Vitamin D deficiency; and, death rates; are both disproportionately higher in elderly Italians, Spanish, Swedish Somali, and African Americans? A connection? Research urgently required! https://www.bmj.com/content/368/bmj.m810/rr-46
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James Larsen
replied on 01 May, 2020
There is a tendency to see a vitamin as a lesser intervention than a drug. Yet, vit D can have a huge effect on outcomes: Look at POST-HOC ANALYSIS OF VITAMIN D STATUS AND REDUCED RISK OF PRETERM BIRTH IN TWO VITAMIN D PREGNANCY COHORTS COMPARED WITH SOUTH CAROLINA MARCH OF DIMES 2009-2011 RATES CL Wagner1, et al
Robert Brown
commented on 11 April, 2020
Hi Bob Martens Re vitamin D - logically given vit d has significant roles in respiratory function; it will factor in COVID-19 infection; thus infection, hospitalization, and death rates, will be impacted by time of year/ latitude / cloud cover / altitude / pollution etc. I graphed Spain and Italy by region against various COVID-19 metrics - results are interesting - but other factors are clearly shadowing and complicating COVID-19 outcomes.
Robert
commented on 11 April, 2020
HI It is excellent this paper confirms the results in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A posted on 24th March. https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and as also referred to in this BMJ letter https://www.bmj.com/content/368/bmj.m810/rr-46 (I struggle to understand why you moderated out my previous post pointing this out.)
Robert Brown
commented on 11 April, 2020
HI It is excellent this paper confirms the results in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research Brown R*, Sarkar A posted on 24th March. https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and as also referred to in this BMJ letter https://www.bmj.com/content/368/bmj.m810/rr-46 (I struggle to understand why you moderated out my 2 previous posts pointing this out - I have put in a formal complaint to Research Square - there are no reasonable grounds for this comment to be deleted.)
Robert Brown
commented on 11 April, 2020
HI I posted a comment to a preprint as below congratulating the authors and referring them to a previous paper on the same topic – and that their results independently confirmed the outcomes. The comment has twice been moderated out. Is suggest this is unacceptable and misplaced. I have raised the matter with our President Michael Crawford https://www.imperial.ac.uk/people/michael.crawford With many thanks Robert Brown
Robert Brown
commented on 11 April, 2020
Hi it is excellent this paper confirms the vitamin D levels may factor in COVID-19 aka corona virus mortality. It adds to evidence that the difference in mortality between Southern and Northern Europe may in part be due to higher intakes and supplementation in 'Northern Euorpe as we postualted in Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality?' – An urgent call for research Brown R*, Sarkar A https://www.mitofit.org/images/e/ec/Brown_et_al_2020_MitoFit_Preprint_Arch_doi_10.26214_mitofit_200001.pdf and further discussed in a letter to the BMJ. https://www.bmj.com/content/368/bmj.m810/rr-46 The likely importance of the pandemic of vitamin D deficiency in COVID-19 infection progression and mortality, is hugely under appreciated. Research is required as a matter of urgency. (Whoever keeps deleting my attempts to make this response, please desist - I am assured it is not the Authors)
Claude Lubicki
commented on 15 April, 2020
Hi, Thank you for this paper showing an apparent inverse relationship between Vitamin D serum levels and Covid-19 mortality in 20 EU countries. This identifies again the potential role of vitamin D mitigating this viral infection. There is only point which I am not sure to understand from your paper is about the ACE-2 receptor. My understanding is that VDR is a repressor of ACE-2 and not an activator. ref: G.V. Glinsky: Genomic-guided molecular maps of coronavirus targets in human cells: a path toward the repurposing of existing drugs to mitigate the pandemic Regards, Claude
John G
commented on 15 April, 2020
Very good start on research. Obviously needs more research. The bottom chart is confusing as to what x and y are. titles for axis would help.
Steve Peat uk
commented on 19 April, 2020
The report is interesting, and my question why world health authorities do not test people Vitamin D levels in all age groups and ethnic groups. The governments need to test patients on people who suffering with the virus to see the relationship how patients needing oxygen have lower Vitamin D levels compared with mild cases. The next question to help treat patients could vitamin D injections given to patients who have started suffering from the virus could prevent them deteriorating to a level to need oxygen. The last question we have seen elderly people across the world include people over 100 survived the coronavirus compared to patients in the 50s, I.e, what bood chemistry these older people have to survive the coronavirus compared with other groups of people who have died with the virus. We need medical staff to carry out tests to investigate this report on patients include DNA how Vitamin D affects the body.
Louise
commented on 24 April, 2020
I have with much interest followed vitamin D studies and research for the past 6 years. Knowing that every one of our 70 trillion and more cells has a vitamin D receptor explains the importance of that hormone. Exciting.
Dr. David Bilstrom
commented on 28 April, 2020
I have been researching this also. Found a few studies - two are about patients on ventilators. 300,000 IU of vitamin D with an intramuscular injection; into the muscle. saw a 50% reduction in the death rates. Half the people were saved from dying with one dose of vitamin D. For these very sick people on ventilators, the average time was 10 days less for those. Effect of High-Dose Vitamin D on Duration of Mechanical Ventilation in ICU Patients https://pubmed.ncbi.nlm.nih.gov/31531088/ ************** High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. Journal of Clinical and Translational Endocrinology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939707/ ******************* Blood clotting an issue with Covid19 - Vitamin D as an anticoagulant https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069050/ ****************** Wrote a blog that includes video from me that summarizes these findings: https://bit.ly/Save-Lives-Injectible-VitaminD
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Eduardo Quinteros
replied on 02 May, 2020
But nothing was probed in those studies !
Michael G Crist
replied on 17 May, 2020
Consider the following 2015 [South] Korean study as well: "The Association Between Vitamin D Deficiency and Community-Acquired Pneumonia" https://journals.lww.com/md-journal/fulltext/2019/09200/the_association_between_vitamin_d_deficiency_and.65.aspx
Zhou Fang
commented on 01 May, 2020
This paper is a textbook example of correlation != causation. Absolutely terrible.
View 1 reply
Michael G Crist
replied on 17 May, 2020
Naturally... PRC would cast doubts on anything other than THEIR research & remedies!
Fraser Andrew
commented on 01 May, 2020
Given the strength of the association, the results from the other studies mentioned above, and the current emergency, surely one would not advise against Vitamin D supplementation, would one, Zhou Fang?
Linnéa Palme
commented on 02 May, 2020
I wrote this in Swedish on my facebook 24th of mars and same thoughts on my blogg april 22nd It´s on Covid-19- and three hormons- Vitamin D- Testosterone and Estrogen in this way I could se the age and groups early in February and also why not children got Covid-19. https://linneapalme.wordpress.com/2020/04/22/vem-drabbas-mest-och-varfor-covid-19/ and on april 25th I wrote https://linneapalme.wordpress.com/2020/04/25/den-nya-klimatfragan/
morris maizels
commented on 02 May, 2020
The table alleging a relationship between Vit D levels and mortality may have some statistical significance, but it appears that 2 outliers with low Vit D levels and mortality rate account for nearly of the relationship. As much as I would like to, I dont find this at all compelling evidence. Have I missed something?
VASSARAS ALEXANDROS
commented on 02 May, 2020
Excellent work ! We are working on a similar work ! and the findings are similar ! So the country with less deaths per million has also the most vitamin D levels in the population !
Haithum Ali
commented on 02 May, 2020
So I am totally convinced that vitamin D plays a crucial role in Cov19 defence, only time will tell, According to CDC, 33% of people hospitalised Cov19 in the US were African American who only constitute 13% of the population, by 45% were white people who make up 76% of the population. also, Somali immigrants living in Stockholm Sweden make up 40% of related Cov19 deaths, Sweden is a country that is at a northern latitude (57N' around 1900 sunlight a year and Somalia is 2N' 3200 sunlight a year) which increases vitamin D deficiency, this rate of hospitalisation is really high considering Somali’s make up 0.84% of Stockholm population. There is a very good reason why vitamin D have linked with cov19, there is data to suggest that vitamin D is protective against respiratory infection. Vitamin D an important role in the immune response and people with lower vitamin D may have a weaker immune response. People talk about that warm climate is good for killing the virus and cold is bad making the virus alive. but, our body temperature is 37 degrees Celsius and we know c19 can survive in that so if it's 37C or 40C outside, It would probably survive.
Gregory Joffe
commented on 04 May, 2020
Vitamin D deficiency in the majority of cases is caused by Magnesium deficiency, which is usually in the mentioned groups of the population. Thus recommendations for vitamin D should come together with recommendations for magnesium supplements.
Josef Dietl
commented on 04 May, 2020
Would you kindly label your graphs?
Peter Garvin
ORCiDcommented on 05 May, 2020
With all respect, this study can't be used neither to support nor reject the hypothesis. If this would have been a wriiten exam in epidemiology, I would have failed the students for the following reasons: 1) Data clearly suggests that is not appropriate to use t-test. As you all know, incidence rates are seldomly normally distributed. Having a STDEV that exceeds the mean is not a good sign, it indicates that the entire analysis is idependent on one or a few outliers. 2) Number of tested persons with positive result is not a good proxy for number of cases in the population. It has been clear from the start the different countries has applied different approaches regarding number of tests as well as which groups should be tested. (Not to mention the specificity and sensitivity issues). 3) Since the mortality rates vary highly with age, analyses should have been age standardized in some way. It is almost sad to see that the authors claim to minimize confounding without taking demographics into account. This could have been easily done, stratifying the material based on age groups and standardize for age specific vitamin D reference interval (or at least estimations of age specific intervals). 4) The correlation in Figure 2 on mortality implies that, given that the correlation is true, you could have a negative mortality rate. Clearly, linear fitting is not always ideal, and this could, I am afraid, be used as a school book example to illustrate that. Apart from the note on philosophy of science that a correlation cannot be "very significant" as stated, the coefficient seems to be highly depending on one single outlier. (Further, it seems that the different countries are not weighted in relation to population size, which supersizes the impact of small countries). I could go on, but I think my message is clear. I have no wish neither to support or reject the hypothesis on vitamin D. There is a need for carefully considered and planned analyses to increase our understanding. This paper does simply not meet the scientific standard needed to conclude that vitamin D supplementation should be used to protect against COVID–19 infection. It is not the design per se that limits the value (which by the way is ecolological rather than cross-sectional as stated), it is the amount of methodological flaws in the analyses.
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Wynn Quon
replied on 08 May, 2020
These are really good points. Thanks for this. Everyone wants so much to believe. The original authors should address these shortcomings pronto.
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Michael G Crist
replied on 17 May, 2020
How many will die unnecessarily within the next three months because of this delay?
stephen lee
commented on 07 May, 2020
Clearly many factors, e.g. skin colour and type of dress, affect winter Vitamin D levels in northern Europe. Income, or wealth, is another such variable, as very many of the richer Northern Europeans typically manage to relocate to somewhere considerably more sunny for at at least a couple of weeks in the winter, as anyone who has been to SE Asia, the Caribbean, or the Canary Islands In January will have noticed
Benjamin Layton
commented on 13 May, 2020
I've been looking at the data for a while as well, Vitamin D3 is going to play an important part in fortifying the aging populations and B12 will need to be examined as well due to the antimicrobial properties of cobalt and cobaltamine. The virus in general seems to be somewhat resistant to damage from sources of vitamin c, but oxidized vitamin c seems to still be an efficient way to transport reactive oxygen species into cells for their intended function. We need to gather data from a wide population and have their vitamin levels examined as well as a self report of how sever they felt their symptoms to be.
Dr Gary Barker
ORCiDcommented on 15 May, 2020
A really interesting study. Can the data underlying figs 1 and 2 be shared please? It would be helpful if they could be looked at by the wider community.
Lynne
commented on 15 May, 2020
Regarding Covid19 in African and Afro Caribbean communities, has it is anyone looked into the relevance of sickle cell trait? It is a mild version of sickle cell disease which many sufferers are unaware they have. It can, however, be very dangerous if the person becomes short of oxygen. I am not a scientist, just a concerned layperson but this seems very relevant to me and I do not know whether this has been looked into.
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Sharon
replied on 16 May, 2020
Hello I have also been wondering whether there's a link between the sickle cell trait and Covid outcomes.
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Patricia Jones
replied on 19 June, 2020
I have also been wonderung about sickle cell and thaleassemia. Has anybody look at at anti phospholiped auto immune disorder ?
William J. Kelleher
commented on 16 May, 2020
You have a typo in the extract... you use mmol/L instead of the proper nmol/L. If someone's vitamin d level were that high, they'd be dead.
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William J. Kelleher
replied on 16 May, 2020
*abstract
Zim Laboratories
commented on 19 May, 2020
According to a study, Vitamin D3 has the potential to help the human body fight against COVID-19. It reduces the occurrence of fewer upper respiratory tract infections including influenza. In several scientific studies, it has also been reported that Vitamin D3 supplement is beneficial in reducing the risks of Influenza, Dengue, hepatitis C, Herpes, HIV, RSV, etc.
Meg
commented on 22 May, 2020
I had a very severe and unusual flu 4 years past onset was fever, a dry hacking cough i also had a sudden loss of sensation on one side of my body, crazy dreams or hallucinations at home 3 days with the fever then i happened to have a rapid decline ending up hospitalized in a very small rural hospital with very limited resources I couldnt breath well, I was dehydrated from fever I.V started, was found to have severely low salts from what they thought was overhydration, my BP was terribly low 80/43 with fast pulse, it felt as though something was constantly squeezing my throat and as though someone sat on my chest, the coughing was wretched, my vision was affected and blurred, no swabs of any sort were taken as they didn't have any, clarithromycin type drug was given by I.V. as well as prednisone to open my airways through I.V. my windpipe felt opened in a matter of half hour or so, my blood panel showed severely low VITIMIN D it took me months to recover, they released me to my mother my mom feared i would die if they kept me!, the sent me home with zpac, prednisone, and vitimin D and calcium intake instructions. My Mother kept me with her for 2 months and nursed me back to health using B12, 4000 ui of Vitimin D which I needed to take for a year, i now take a daily dose of 2000 ui, my husband is a smoker and ive had him on 4000 ui per day since covid began in Canada here. i thought i would share my story that you all may find my story interesting as i must say i thought i was going to die from that respiratory flu i had, and perhaps if i wasn't deficient in Vitimin D maybe i would have gotten that sick I almost died at the age of 42. Good luck with your research I do believe you are on to something!
Burton C Butterfield
commented on 27 May, 2020
is there enough data which compares the mortality rate in patients who have normal vitamin D before concluding a positive correlation to the rate in those northern European countries
John Sloss
commented on 10 July, 2020
I am interested in the fact that bats from whom many researchers believe the virus originated are short of vitamin D. This is not surprising as they are nocturnal and many roost in caves. Although I am a retired Consultant in Microbiology FRCPath and my knowledge of immunology is somewhat limited I believe there is some published evidence of vitamin D and T cell function. It therefore seems to make sense to supplement high latitude human populations with vitamin D a relatively safe cheap and available measure. What of course would be interesting would be to measure vitamin D levels in patients with poor outcomes in corona virus
sceptic
commented on 15 July, 2020
We should combine it also with regional pollution levels https://www.dutchnews.nl/news/2020/07/farm-and-vehicle-emissions-made-coronavirus-worse-in-south-study/
Pg
commented on 01 August, 2020
Corona: prevent, vitamin d? No!
Ntombikayise Precious Bhengu
commented on 08 August, 2020
Excellent research! Does this mean, if people took supplements of vitamin D, in addition to wearing protective gear, social distancing, sanitizing and washing hands every now and then, it would reduce their chances of people getting infected with COVI-19?
Philip Barr, MD
replied on 07 May, 2020
Thank you for publishing this helpful data. While the physiology of Vitamin D-2 and D-3 has been known for decades in promoting both innate and adaptive immunity , specific research on COVID-19 has been lacking. Advising physician support in testing levels to reach optimal, as you suggest, is well-intended. Anywhere that physician services are hard to schedule, as during this stay-at-home pandemic, would allow for a safe generic recommendation of 2-4,000 IU per day orally until a level can be measured. Again, thank you for this altruistic much needed service! Philip Barr, MD USA
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Michael G Crist
replied on 17 May, 2020
Vitamin D2 should be excluded from consideration at this point. Multiple studies have indicated that it is a considerably weaker choice of Vitamin D supplementation. Discussion should be limited to Vitamin D3 only, specifically with regard to COVID-19.
Courtney
replied on 07 May, 2020
You make a really good point, but I feel like dietary lifestyles should be looked at as well. Examples: Vegetarians and vegans don’t eat enough vitamins, nutrients, and/or minerals their body needs. And what a lot of people lack whether they eat meat or not is iron so that shouldn’t definitely be looked into and researched as well. Apart from vitamin D, the vitamins/minerals that both vegetarians typically need: Iron, Zinc, and Magnesium. Yes, while we need other vitamins and minerals, the above minerals are the ones we need the most over the other minerals. Also, with Vitamin B6 I think you have to be careful with that where it is necessary but if you take too much, it’s not good for the body.
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Mark
replied on 14 May, 2020
Courtney, do you have significant clinical data to show what you're saying about vegetarians and vegans RE vitamins? In fact, I'd be even more interested to see something significant that shows specific deficiencies vs omnivorous diets. Otherwise, that's quite the claim you're making there.
George
replied on 15 May, 2020
I would also agree about looking into other vitamins and the overall impact of diet. At the same time, I'd raise the same questions as below about a source of the claims towards vegetarian and vegan diets as the literature seems to imply a different picture: Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967195/ From the study's conclusion: 'In conclusion, results concerning body weight, nutritional intake, nutritional quality and quantity are in line with the literature on restricted and prudent diets versus unrestricted omnivorous diet. The use of indexing systems, estimating the overall diet quality based on different aspects of healthful dietary models indicated consistently the vegan diet as the most healthy one.'
Linda
replied on 16 May, 2020
Vitamin B6, like other B vitamins, is water soluble. Any excess is easily excreted, and not likely to cause problems.
Caroline
replied on 27 May, 2020
Do you think that individuals that have genetic problems with their red blood cells like stomatocytosis can be more sick in covid-19 because of the lack of b12 that works normal in others without stomatocytosis.
Mrs Rebecca Bradshaw
replied on 09 June, 2020
Hi, I think I had covid mildly last year lasting for two months. I had a blood test that picked up that my vitamin D was not just low but through the floor. I read an article in the guardian saying that someone else suffering from covid had a very low vitamin d deficiency after catching it. What if covid-19 causes the body to reduce its vitamin d level? This all people that catch it appear to have a low vitamin d level?
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Jan Claessens
replied on 11 June, 2020
Which Corona strain where you infected with and when was de bloedtest taken? If you stayed inside for a long time, very low D is quite normal...
[email protected]
replied on 26 June, 2020
With higher B12 You also have more NK s that will help with covid 19 . I take 2500 IE Vitamine D abd once a year i make a B 12 Cure.
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