Preventing a covid-19 pandemicBMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m810 (Published 28 February 2020) Cite this as: BMJ 2020;368:m810
All rapid responses
I am grateful to Ms Jane Robertson for telling me that what I suggested in March is now happening.
I ask the powers that be:
How many months does it take to implement a simple suggestion? A medical officer of health would have done it within a couple of days.
And I ask: this tardiness has been responsible for spread of the disease, possibly, deaths.
Will the House of Commons determine who was responsible for damaging public health?
Competing interests: No competing interests
JK Anand previously suggested at the start of the UK’s response to the epidemic that sewage be examined.
I thought they would like to know about the following that a government-led project is successfully detecting traces of coronavirus in sewerage, providing an early warning for local outbreaks across the country
Competing interests: No competing interests
I read with interest this article and related rapid responses, and I would like to contribute with some observations and hypotheses that will hopefully take us closer to understanding the role of smoking in the ongoing spread of the disease COVID-19.
But first let us note that medicine is a statistical science, where sometimes false statements are embedded among true relationships. For instance, the same studies that reveal the risk factors of comorbidities such as obesity and diabetes on the prognosis of COVID-19, seem to tiptoe around the issue of data in relation to alcohol consumption and smoking habits.
Indeed, in the New York City area, mortality has been null for patients younger than 20 years but above 30% for those over 70 yr. old . In addition, preliminary analysis suggests that serum 25-hydroxyvitamin D status may play a role in COVID-19 fatality , which confirms clinical observations among patients admitted to hospital in England that being overweight and non-Caucasian (i.e. Blacks, Asians, Hispanics or the like) is associated with a higher odds of testing positive for COVID-19 , while surprisingly, a regular smoker has reduced odds. The same is true among an ample cohort of patients from a hospital in Wuhan, China: few patients had a current or former cigarette smoking history . Notably, it might seem that alcohol drinking also has a protective effect against COVID-19 . Similar results can be concluded from a multicentre cohort study throughout Spain .
Exposure to tobacco has consistently been associated with several autoimmune diseases, including systemic lupus erythematosus , yet a lower risk of developing inflammatory and neurodegenerative diseases such as Parkinson’s. The mechanism by which this occurs is unclear, although it has been recently suggested that nicotine regulates the ACE2 enzyme pathway involved in the “cytokine storm syndrome”, a systemic inflammatory response in many COVID-19 patients .
However, we prefer to hypothesize that it is not the nicotine, but the tobacco virus that cross-react with coronaviruses, and thus, may play a key role in the prognosis of COVID-19 infection.
Although it is usually claimed that tobacco plants cannot host human pathogens, tobacco virus has been described as viable in cigarettes and recovered from smokers' saliva . In line with our hypothesis, it is suspected that immunological cross-protection from previous exposure to A-type influenza viruses other than H1N1 (e.g. 1889 pandemic) may have played a role in the low mortality rates among the middle-aged and older individuals during the Spanish Flu . Similarly, evidence of SARS-CoV-2 immunity induced by antibodies from memory B cells of an individual who was infected with SARS-CoV in 2003 , probably stems from the fact that spike proteins of SARS-CoV-2 and SARS-CoV are structurally very similar .
As we have previously highlighted, shape and size matter when it comes to determining the characteristics of nanoentities . In this regard, we note positive-stranded RNA tobacco virions (for which tomatoes, peppers, and cucumbers are also a host) are hollow rod-shaped particles about ~300 nm in length and ~18 nm in diameter , while the positive-stranded RNA SARS-CoV-2 virus has round crown-like appearance and a diameter of approximately 100 nm , which is perhaps consistent with the speculation that they share structural similarity of antigenic determinants. In this regard one should note that smokers have a higher level of serum immunoglobulin IgG antibodies , the receptor for viruses that cause cold-like symptoms, fever, sore throat, bronchitis, pneumonia, diarrhea, and conjunctivitis, much like the COVID-19 . As such, cross-reactivity against coronaviruses has recently been demonstrated by connecting human ACE2 to immunoglobulin IgG1 . But, unfortunately, on the sad side is the fact that ACE2 expression mediates both in infections by coronaviruses and influenza A , and could pose a higher level of infectivity for vaccinated individuals . This could explain the worsening of disease among the elderly with comorbidities, which are included among the high priority groups for routine influenza vaccination by many national health authorities. If confirmed, this observation would have implications for annual vaccination recommendations and policies, given the little impact on mortality rates that would have occurred during flu season had none of the elderly been vaccinated .
In conclusion, I have described what I believe is the first instance of tobacco virus is confirmed as the cause of smoking oddity when it comes to coronavirus disease. If this is proven to be correct, there is a possibility of effective adaptive immune responses in a naïve vaccination model . Something similar has been developed against avian influenza [23, 24].
We finish by noting that tobacco and tomatoes are extensively cultivated in the Mediterranean area…I let the reader wonder whether this has something to do with the significant regional differences in the COVID-19 epidemic.
1. S. Richardson, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA (2020); doi:10.1001/jama.2020.6775
2. A. Daneshkhah, et al. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. (2020). medRxiv 2020.04.08.20058578; doi:10.1101/2020.04.08.20058578
3. A. L. Darling, et al. Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). (2020). medRxiv 2020.04.29.20084277; doi:10.1101/2020.04.29.20084277
4. T. Chen, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 368, m1091 (2020)
5. S. Liu, et al. Characteristics and Associations with Severity in COVID-19 Patients: A Multicentre Cohort Study from Jiangsu Province, China. (2020). https://ssrn.com/abstract=3548753; doi:10.2139/ssrn.3548753
6. J. M. Casas Rojo, et al. Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network. (2020). medRxiv 2020.05.24.20111971; doi:10.1101/2020.05.24.20111971
7. D. S. Majka & V. M. Holers. Cigarette smoking and the risk of systemic lupus erythematosus and rheumatoid arthritis. Ann. Rheum. Dis. 65, 561-563 (2006)
8. K. Farsalinos, et al. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol. Rep. 7, 658–663 (2020). doi:10.1016/j.toxrep.2020.04.012
9. F. Balique, et al. Tobacco mosaic virus in cigarettes and saliva of smokers. J. Clin. Virol. 55, 374‐376 (2012)
10. S. E. Mamelund, et al. A Missed Summer Wave of the 1918-1919 Influenza Pandemic: Evidence From Household Surveys in the United States and Norway. Open Forum Infect. Dis. 3, ofw040 (2016)
11. D. Pinto, et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature (2020). doi:10.1038/s41586-020-2349-y
12. C. Wang, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nature Comm. 11, 2251 (2020)
13. C. Martinez-Boubeta, et al. Learning from Nature to Improve the Heat Generation of Iron-Oxide Nanoparticles for Magnetic Hyperthermia Applications. Sci. Rep. 3, 1652 (2013)
14. K. C. Holmes. Flexibility in tobacco mosaic virus. Ciba Found Symp. 93, 116‐138 (1983)
15. S. Prasad, et al. Transmission electron microscopy imaging of SARS-CoV-2. Indian J. Med. Res. 151, 241-243 (2020)
16. R. Liu, et al. Humans have antibodies against a plant virus: evidence from tobacco mosaic virus. PLoS One 8, e60621 (2013)
17. J. Sui, et al. Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants. J. Virol. 79, 5900-5906 (2005)
18. C. Lei, et al. Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat. Commun. 11, 2070 (2020)
19. P. Yang, et al. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci Rep. 4, 7027 (2014)
20. L. Zhang & Y. Zhang. Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease 2019 (COVID-19). (2020). doi: 10.20944/preprints202003.0307.v1
21. B. Fireman, et al. Influenza Vaccination and Mortality: Differentiating Vaccine Effects From Bias. Am. J. Epidemiol. 170, 650–656 (2009)
22. M. D. Langowski, et al. Optimization of a Plasmodium falciparum circumsporozoite protein repeat vaccine using the tobacco mosaic virus platform. Proc. Natl. Acad. Sci. U.S.A. 117, 3114-3122 (2020)
23. J. K. Mallajosyula, et al. A Single Dose TMV-HA Vaccine Protects Mice from H5N1 Influenza Challenge. Int. J. Vaccine Res. 1, 6 (2016)
24. Y. Ceballo, et al. High accumulation in tobacco seeds of hemagglutinin antigen from avian (H5N1) influenza. Transgenic Res. 26, 775‐789 (2017)
Competing interests: No competing interests
Hypoalbuminemia is frequently observed in conditions like diabetes, hypertension and chronic heart failure, the cohort which is hardest hit with COVID-19 infection.(1)(2)(3) In our vast experience in India in a cardiac care unit, we have observed significant benefits of carefully administered albumin in patients with acute coronary syndrome, sepsis and septic shock.(4) Based on our observation we propose a trial of slow IV albumin with diuretics in COVID-19 patients suffering from ARDS along with hypoalbuminemia.
Amongst COVID-19 patients, those with low albumin levels have a poorer prognosis and low albumin levels are seen in 80% of the nonsurviving patients.(5) Its association with poor outcomes thus is conceivable since serum albumin maintains plasma oncotic pressure and acts as a carrier molecule for various endogenous and exogenous compounds. It has significant antioxidant properties responsible for maintaining plasma redox state.(6)
Although hypoalbuminemia is often an effect rather than the cause of the underlying pathology, targeted therapy with intravenous albumin has shown to improve serum albumin levels and improve respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment (SOFA) score.(7) In patients with acute lung injury in spite of altered capillary permeability, intravenous administration on IV albumin with diuretics improved oxygenation via increase in colloidal oncotic pressures, improved cardiac output and better ventilation–perfusion matching.(8)(9) A small pilot study has also shown favourable metabolic profile in patients of acute lung injury treated with I.V. albumin. (10)
In view of its abovementioned benefits, its trial is warranted in the current scenario of the COVID-19 pandemic. We have already registered a trial under Clinical trial Registry-India to examine the effect of intravenous infusion of albumin with diuretics in COVID-19 patients with respiratory insufficiency.
Competing interest : No competing interest.
1. Gopal D, Kalogeropoulos AP, Georgiopoulou VV, Tang WWH, Methvin A, Smith AL, et al. Serum Albumin Concentration and Heart Failure Risk. Am Heart J. 2010 Aug;160(2):279–85.
2. Stranges S, Rafalson LB, Dmochowski J, Rejman K, Tracy RP, Trevisan M, et al. Additional contribution of emerging risk factors to the prediction of the risk of type 2 diabetes: evidence from the Western New York Study. Obesity (Silver Spring). 2008 Jun;16(6):1370–6.
3. Guan W-J, Liang W, Zhao Y, Liang H, Chen Z, Li Y, et al. Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis. 2020.
4. Sharma YP, Krishnappa D, Kanabar K, Kasinadhuni G, Sharma R, Kishore K, et al. Clinical characteristics and outcome in patients with a delayed presentation after ST-elevation myocardial infarction and complicated by cardiogenic shock. Indian Heart Journal. 2019 Sep 1;71(5):387–93.
5. Huang Y, Yang R, Xu Y, Gong P. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv. 2020 Mar 5;2020.02.27.20029009.
6. Taverna M, Marie A-L, Mira J-P, Guidet B. Specific antioxidant properties of human serum albumin. Ann Intensive Care. 2013 Feb 15;3:4.
7. Dubois M-J, Orellana-Jimenez C, Melot C, De Backer D, Berre J, Leeman M, et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study*: Critical Care Medicine. 2006 Oct;34(10):2536–40.
8. Uhlig C, Silva PL, Deckert S, Schmitt J, Abreu MG de. Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care. 2014 Feb;18(1):1–8.
9. Geer RT, Soma LR, Barnes C, Leatherman JL, Marshall BE. EFFECTS OF ALBUMIN AND/OR FUROSEMIDE THERAPY ON PULMONARY EDEMA INDUCED BY HYDROCHLORIC ACID ASPIRATION IN RABBITS: The Journal of Trauma: Injury, Infection, and Critical Care. 1976 Oct;16(10):788–91.
10. Park Y, Jones DP, Ziegler TR, Lee K, Kotha K, Yu T, et al. Metabolic effects of albumin therapy in acute lung injury measured by proton nuclear magnetic resonance spectroscopy of plasma: A pilot study*: Critical Care Medicine. 2011 Oct;39(10):2308–13.
Competing interests: No competing interests
On 12 March in a rapid response, I suggested that the sewage be examined to form an idea of where there are excreters of Coronavirus.
No one has debunked the suggestion. It is not a brand new idea - it has been used, for example, in Poliomyelitis epidemiology.
Is PUBLIC HEALTH ENGLAND carrying out this work? 
And if not, is it not criminally negligent?
1 Mallapaty S. How sewage could reveal true scale of coronavirus outbreak. How sewage water testing could also be used as an early warning sign if the virus returns. Nature 2020 Apr 9;580:176-7.
Competing interests: Resident in Pace Britannia
Vitamin D may directly prevent COVID-19 from entering lung epithelial cells; this means that Vitamin D might be a specific treatment (in addition to its potential role in prophylaxis). Here is the rationale:
1. COVID-19 enters lung cells by binding to ACE2 receptors .
2. ACE2 receptors utilize a specific interleukin (IL-6) when normally activated .
3. Blockade of IL-6 by tocilizumab may be an effective treatment for COVID-19 .
4. Vitamin D reduces IL-6 production in monocytes (and, presumably, macrophages) .
This provides a rationale for administration of Vitamin D (eg by intramuscular injection) as treatment in acutely ill patients with COVID-19.
1. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875–879. doi:10.1038/nm1267
2. Senchenkova EY, Russell J, Yildirim A, Granger DN, Gavins FNE. Novel Role of T Cells and IL-6 (Interleukin-6) in Angiotensin II-Induced Microvascular Dysfunction. Hypertension. 2019;73(4):829–838. doi:10.1161/HYPERTENSIONAHA.118.12286
3. Michot JM, Albiges L, Chaput N, et al.Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report. Annals Oncology. 2020. doi: https://doi.org/10.1016/j.annonc.2020.03.300.
4. Sadeghi K1, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36(2):361-70. doi:10.1002/eji.200425995
Competing interests: No competing interests
I'm responding to the response made by Emilio Maestri (endocrinologist) on 12 March 2020 regarding contradictory studies using 'vitamin' D supplementation.
I have not read the references he has cited but, although I am not a nutritionist, I have read enough over the years to know that supplementation of just one micronutrient in large doses is not necessarily advisable and may well give poor results. In the case of 'vitamin/hormone' D, I am aware that a deficiency of magnesium, said to be rife in developed countries (due to modern farming methods and depletion through what we call "stress"), can manifest also as a vitamin D deficiency so that increasing supplemental dose of vitamin D will not have the desired effect precisely because the deficiency concerned is magnesium (which is needed to 'activate' vitamin D.)
Furthermore, in the case of trying to improve osteoporosis with supplemental vitamin D, there is the necessity of vitamin K (in the form of K2) which 'directs' dietary calcium in the presence of vitamin D to the bone rather than soft tissues. Vitamin K is found, for example, in dark green leafy vegetables in the form of K1, but is not always easily converted to K2 in the body and therefore animal sources are preferable, a factor which may produce even more health problems in the future with the increasing popularity of a vegan diet.
As I have said, I am not a nutritionist and may have simplified my explanations somewhat, but merely wished to point out that micronutrients work in harmony with one another and studies focusing on just one discrete micronutrient are likely to have already failed at the outset.
Competing interests: No competing interests
Prevention and Cure of Covid 19? – A Discussion about Vitamin D Deficiency.
Fiona Smith 7th April 2020
Let’s be clear about this please, I’m not a doctor… But, with years of experience of being a loving mother and registered manager in charge of care for thousands of our older generation, I have had to live with the constant spur of an enquiring mind, especially in relation to procuring best care and support for the people I had responsibility for…
Having recently taken early retirement, my partner and I spent much of February 2020 travelling the Far East; we lived and breathed the emergence of Covid 19 through news and internet. Hand washing and mask wearing was a daily, minute by minute duty. But, on our travels through the heat and sunlight of Cambodia, Lao and Thailand, not only did we learn from locals that the Chinese were their most frequent visitors, but it was also evident they have close economic ties – widespread Chinese, housing and road construction work was heavily in progress; if Covid 19 was going to come knocking on any door, these three Countries would likely be the first to experience a pandemic. But, no pandemic appeared then, or even now. So, WHY?
Sunlight brings the benefit of vitamin D through its interaction and chemical synthesis with our epidermis – the benefits of which go far beyond the production of vitamin D. But, ‘cutting to the chase’, we theorised back then in February, that optimum levels of vitamin D, not only make you feel great, but medical studies (Martineau 2017) suggest it can help prevent respiratory tract infections; we also wondered whether optimum levels of vitamin D could make symptoms of Covid 19, asymptomatic or just extremely mild?
It is known that the death rate from Covid 19 is higher in men than women. It is also known that obesity, diabetes, high blood pressure and old age make your chances of survival more difficult too. It is my opinion that vitamin D deficiency is likely to be the reason, firstly that those with obesity, diabetes and the elderly have suffered more severe conditions related to Covid 19, but that others who don’t have known underlying conditions have suffered such terrible fates too, and these are my reasons:
1. Vitamin D deficiency is prevalent in people with high blood pressure, diabetes and obesity
2. Vitamin D deficiency is prevalent in the winter months due to lack of therapeutic levels of sunshine.
3. The overuse of sunscreens has reduced vitamin D absorption in summer months.
4. Women generally have higher vitamin D levels than men because oestrogen encourages the uptake of this vitamin into the body.
5. Older people don’t absorb vitamin D as effectively as younger people, and are often severely deficient. Generally older people who regularly sunbathe, not only live longer, but are much healthier, suffer less obesity and blood pressure problems and are less likely to suffer bone fractures – I have made this observation from 15 years of caring for the elderly.
I therefore suggest the following measures be taken:
1. Every new suspected case of Covid 19 be tested for vitamin D deficiency, and treated bringing vitamin D status to optimum levels. This would require several measured therapeutic doses of vitamin D, or several doses of full body UVB exposure.
2. Government advice be updated to encourage the UK population to take sensible levels of sunshine therapy and/or vitamin D supplementation at higher levels (4000iu – the upper level recommendation on the NHS website). People who live in flats should be allowed a permit to sunbathe in public areas.
3. Therapeutic vitamin D supplementation be provided to frontline staff and the most vulnerable.
4. Medical trials be actioned immediately, with results available within weeks regarding the value of therapeutic levels of vitamin D supplementation.
Competing interests: No competing interests
The role of vitamin D in the prevention of COVID-19: Stay rational during an urgent epidemic outbreak Re: Preventing a covid-19 pandemic
In the prevention of COVID-19 pandemic, Robert A Brown suggests that vitamin D may contribute to the prevention of COVID-19 and should be applied in a wider clinical practice immediately. The reason was that the higher mortality rates in Spain and Italy in comparison with northern European Countries may arise from vitamin D deficiency.  However, I have the same concerns as George Trovas.  Although there is probably a correlation between the level of vitamin D and the epidemiological data of COVID-19, it may be caused by other underlying risk factors.
A meta-analysis reported that vitamin D supplementation alone had no connection with the mortality in adults.  Another study demonstrated that sufficient vitamin D supplementation (≥ 25 nmol/L) did not improve the condition of patients with chronic obstructive pulmonary disease (COPD), compared with patients taking a placebo. Thus the NICE 2018 guideline does not suggest vitamin D. 
The data of global incidence and deaths from the World Health Organization showed that the morbidity of COVID-19 in developed countries is obviously higher than that in developing countries. The data of Max Roser and colleagues indicated that total tests for COVID-19 in Germany was 918 460, which was 454 030 in Italy as of 29 March 2020.  Although Germany has more people than Italy, total tests for COVID-19 per thousand people was 11.13 in Germany, 48.03 in Iceland, and only 7.68 in Italy. On 5 April 2020, daily COVID-19 tests per thousand people in Iceland were 7.24, Italy was 0.58, South Africa was 0.0.5, and India was less than 0.01.  Mild cases took up a major part of the COVID-19 in Germany. Therefore, the high mortality rates in Italy may because many mild COVID-19 patients were not detected. And the most notable point is that low incidence does not mean a mild epidemic: on the contrary, there may be a large number of undetected COVID-19 patients which could make the outbreak worse in developing countries.
In conclusion, vitamin D should not be used blindly in wider clinical trials because of the urgent epidemic. If not, it may cause people to miss more effective treatments, and more valuable research may lose subject resources. Researchers should confront COVID-19 rationally and scientifically, especially when the epidemic is serious.
1. Robert A Brown. (7th April 2020). BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
2. George Trovas. (2nd April 2020). BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
3. Yu Zhang, Fang Fang, Jingjing Tang, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ 2019;366: l4673.
4. Cook R, Thomas V, Martin R. Can treating vitamin D deficiency reduce exacerbations of chronic obstructive pulmonary disease? BMJ. 2019;364:l1025. doi: 10.1136/bmj.l1025.
5. Max Roser, Hannah Ritchie, Esteban Ortiz-Ospina. Coronavirus Disease (COVID-19) – Statistics and Research. Our World In Data. 2020. Retrieved from: https://ourworldindata.org/coronavirus. [Online Resource]
Competing interests: No competing interests
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!
It is posited by contributors [1, 2, 3, 4, 5] to BMJ, ‘Preventing a covid-19 pandemic’, others, [6, 7, 8] and myself,  that vitamin D, and particularly vitamin D deficiency, is a likely factor in the progression, and/ or severity, and/ or mortality of COVID-19; and also may present clinical treatment opportunities.
My preprint, ‘Vitamin D deficiency: a factor in COVID-19, progression, severity and mortality? – An urgent call for research’,  posits, greater vitamin D deficiency <25nmol/L in southern (E.g. Spain and Italy), than northern European Countries (E.g. Germany, Norway, Finland, Iceland), may help account for differentials, in mortality rates per million. Consistent with this, Northern Europeans have higher vitamin D food intakes, food fortification, and supplement more. This is an easily testable posit.
Northerly resident; Europeans with darker skins; BAME, and African Americans; as well as more southerly elderly Spanish and Italians; are often vitamin D deficient. IF, vitamin D deficiency, increases the risk of COVID-19 related; infection, hospitalisation and mortality; one would expect, and indeed sees, higher COVID-19 hospitalisation and mortality, in; dark-skinned (Fitzpatrick scale) northerly residents; those with dress codes that inhibit sunlight; and generally in groups likely to include the ‘D’ deficient.
Whilst data is still sparse, it supports the above contention; albeit lack of distancing, and vitamin D deficiency, may both be contributing factors; for example: “40 % of the reported COVID-19 related deaths occurring in Stockholm involve the Somali diaspora communities”; yet they only represent 0.84% of the population] [10, 11, 12, 13] Data clearly shows, Somalis, and wider immigrant groups, are D deficient, for example, “Vitamin D deficiency ( < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls” [14, 15, 16]
In respect of African Americans, a headline, April 3rd, 2020, states, ‘Early Data Shows African Americans Have Contracted and Died of Coronavirus at an Alarming Rate  “In Chicago, 70% of COVID-19 Deaths Are Black,”  The review, APHA ‘Call for Education and Research Into Vitamin D Deficiency/Insufficiency’, in 2008, noted, “84% of African American men and women (over 65) were vitamin D deficient.” [19, 20, 21] (‘D’ deficiency definitions vary).
In contrast, in continental Africa, whilst Vitamin D deficiency exists, it does not appear to be as widespread as in the United States: “one in five people living in Africa had a low 25(OH)D concentration with use of a less than 30 nmol/L.”  COVID-19 data for Somalia is limited. Tests are done externally: current data; 7 cases, 1 recovered, no deaths.  The first recorded case was confirmed on the 16th of March. Twenty volunteer doctors from Somali National University went to Italy to help fight COVID-19 there. [24, 25] Case numbers in wider Africa are currently relatively low, compared to the most infected countries, but arguably there is insufficient data, or certainty, as to initial infection dates, to, at this point, even postulate as to future COVID-19 infection, or mortality rates, in Africa. 
Differences appear to exist in the metabolism of Vitamin D; ‘The D paradox’;  between Caucasians and African Americans, particularly in terms of bone density. However, the metabolism of vitamin D is complex, and pathways impacting COVID-19 likely differ from those regulating bone densities.
The COVID-19 mortality rate, has very sadly, been high in Italy (15,887 as at 5th April 2020).  A rapid response to the BMJ titled ‘Re: Preventing a covid-19 pandemic Can high prevalence of severe hypovitaminosis D play a role in the high impact of Covid infection in Italy? ’ notes, “700 women aged 60-80 yrs in Italy had values of 25OH vitamin D lower than 5 ng/ml in 27% of the women and lower than 12 ng/ml in as many as 76%.” 
BAME (Black, Asian, Minority Ethnic) persons in the United Kingdom, may be more susceptible. A UK study of 2,249 patients by the ‘Intensive Care National Audit and Research Centre’, noted “Despite making up just 13 per cent of the UK population, a third of patients who fall critically ill with COVID-19 are from black, Asian or minority ethnic (BME) groups.”  Further, sadly, 6 out of 8, UK COVID-19 medical staff deaths, were British Muslims. Hasidic Jews in Israel may also be at higher COVID-19 risk, due to failure to isolate and/ or greater risk of vitamin D deficiency.[33, 34]
Arguably it is urgent, that research is done, to determine if vitamin D deficiency factors in COVID-19, infection, progression, severity and mortality. Vitamin D blood spot tests are cheap. Patient records have to be maintained in any event. The additional work, and risk burden, in taking vitamin D measurements are limited. However, the reward could be very significant, even a ‘game changer’.
Further, any determination that vitamin D factors in COVID-19, incidence progression and outcome, would point to the likelihood of COVID-19 following a seasonal pattern in populations, which would require factoring into determination of Governmental COVID-19 forward planning policies; mortality risk modelling; social distancing polices; and population vitamin D optimisation, including access to outside spaces, to facilitate sensible, ethnicity appropriate, exposure to UVB in sunlight; and/ or free ‘D’ supplementation, at least for the most vulnerable and financially insecure.
COVID-19 studies might comprise:
• Test all COVID-19 patients in hospital/s at a given point in time for Vit D, follow, and report results.
• Take finger prick samples at the same time as COVID-19 test – follow through with laboratory vitamin D tests on the samples of all positives, and an equal number of controls; report results.
• A study using Vit D clinically – test for low vit D – where low supplement with vitamin D3, and/ or as an alternative to above, try a 1,25-active form;  report results.
Vitamin D, could usefully be immediately incorporated into wider clinical nutritional COVID-19 protocols, [36, 37] but, to better understand the role of vitamin D in COVID-19; for the formulation of; treatment, prevention, and wider, policies; the above studies would still be urgently required.
1. Rhein, H. (6th March 2020). BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
2. Cobbold, P. (2nd March 2020). BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
3. Maestri, E., Formoso, G., Da Cas R., Mammarella, F,. Trotta, F. (12th March 2020)
Vitamin D against COVID 19: Clinicians need more than observations and hope. BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
4. Grant, W. (1st April 2020). Can vitamin D supplementation reduce the spread of COVID-19? Try first with health care workers and first responders.: BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
5. Cobbold, P. (8th March 2020). BMJ 2020;368:m810 doi: https://doi.org/10.1136/bmj.m810
6. McCartney, D., Byrne, D. (2020). Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19. Issue: Ir Med J; Vol 113; No. 4; P58. http://imj.ie/optimisation-of-vitamin-d-status-for-enhanced-immuno-prote...
7. Grant, W., Lahore, H., McDonnell, S., Baggerly, C., French, C., Aliano, J., & Bhattoa, (30th March 2020 2nd version) H. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020, 12, 988. https://www.preprints.org/manuscript/202003.0235/v2
8. Isaia, G. (25th March 2020). Possibile ruolo preventivo e terapeutico della vitamina D nella gestione della pandemia da COVID-19 Enzo Medico, Università degli Studi di Torino, Torino,
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Competing interests: No competing interests