Covid-19: Vitamin D a risk-assessment tool and to reduce morbidity and mortality in covid-19 pandemic
Dear Editor,
NHS leaders in England have been advised to “risk-assess” and make “appropriate arrangements” to protect ethnic minority staff who may be at a greater risk of covid-19, as more than half of all deaths of healthcare workers were from an ethnic minority background. A national risk assessment framework would probably take into account ethnicity, age, sex, and other medical conditions, as well as nature of work, risk of exposure, and other factors. The steps to support BAME [black, Asian, and minority ethnic] staff would be developed (1). In our opinion, measuring vitamin D levels in individuals could be an important risk-assessment tool, and vitamin D supplementation might be a useful measure to reduce the risks in covid-19 pandemic.
It is well known that vitamin D reduces the risk of respiratory tract infections through several mechanisms. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza. Evidence supporting the role of vitamin D in reducing risk of covid-19 includes that the outbreak occurred in winter, a time when vitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration (2).
It is estimated that in overall, 13% of population across Europe has vitamin D deficiency (25(OH)D concentration <30 nmol/L) on average in the year, with differences in geographical regions and subpopulations (3). Recent statistical analysis of data obtained from hospitals and clinics across the world evaluated whether a link exists between severe cases of covid-19 that feature cytokine storm and vitamin D deficiency. Age-specific case fatality ratio (CFR) in Italy, Spain, and France (70 yrs ≤ age < 80 yrs) was substantially higher (>1.9 times) than in other countries (Germany, South Korea, China); for the elderly (age ≥70 yrs), Italy and Spain present the highest CFR (>1.7 times that of other countries). As more severe deficiency of vitamin D is reported in Italy and Spain compared to other countries the researchers conclude that elimination of severe vitamin D deficiency could reduce the risk of high CRP levels (4). Recent retrospective multicentre study of 212 cases with laboratory-confirmed infection with SARS-CoV-2 and known serum 25(OH)D levels revealed that serum 25(OH)D level was lowest in critical cases, but highest in mild cases. Vitamin D status was significantly associated with clinical outcomes: higher serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while lower serum 25(OH)D level could worsen clinical outcomes of covid-19 patients. In conclusion, vitamin D supplementation could possibly improve clinical outcomes of patients with covid-19 (5).
In addition to regional differences European data have confirmed, there are differences in vitamin D deficiency also regarding the ethnicity and race, as studies show that the prevalence of deficiency risk among Kurdish and Somali adults living in Finland is quite higher, 50.4% and 28.0% (3). The population survey in the United Kingdom found the prevalence of vitamin D deficiency was 20.0% in white, 40.0% in black and 63.8% in Asian participants(6). It can be assumed that skin colour (increased skin pigmentation inhibits cutaneous synthesis of cholecalciferol, the metabolic precursor of vitamin D), in addition to environmental and cultural factors in BAME subpopulation contribute to elevated risk for vitamin D deficiency, which could be related to higher covid-19 morbidity and mortality in BAME healthcare workers.
In Slovenia we have low covid-19 mortality rate, 47 per million population, compared to UK with 433 per million population.7 More than half of all deaths in Slovenia were from fragile elderly in nursing homes. One month ago, in spite of the fact that there are still no clear clinical data on the relation between vitamin D and covid-19, Slovenian medical community managed to agree to advice all medical doctors to supplement vitamin D in fragile patients in nursing homes, covid-19 patients in hospitals and healthcare workers, especially in covid-19 units. We believe that common sense approach in Slovenia regarding vitamin D supplementation was an important measure for low covid-19 morbidity and mortality in addition to other measures, e.g. social distancing and mandatory use of face masks in the community.
1. Iacobucci G. Covid-19: NHS bosses told to assess risk to ethnic minority staff who may be at greater risk BMJ 2020;369:m1820. doi: https://doi.org/10.1136/bmj.m1820
2. Grant WB, Lahore H, McDonnell SL, et a. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020;12:988. doi:10.3390/nu12040988
3. Cashman KD, Dowling KG, Skrabakova Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr 2016;103(4):1033–44.
4. Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv 2020.04.08.20058578; doi: https://doi.org/10.1101/2020.04.08.20058578
5. Alipio M. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (Covid-2019) (April 9, 2020). https://ssrn.com/abstract=3571484 or http://dx.doi.org/10.2139/ssrn.3571484
6. O’Neill CM, Kazantzidis A, Kiely M, et al. A predictive model of serum 25-hydroxyvitamin D in UK white as well as black and Asian minority ethnic population groups for application in food fortification strategy development towards vitamin D deficiency prevention. J Steroid Biochem Mol Biol 2017;173:245–52.
7. Worldmeter. COVID-19 Coronavirus Pandemic. 5 May 2020. https://www.worldometers.info/coronavirus/
Competing interests:
No competing interests
05 May 2020
Bojana Pinter
MD, PhD, Ms (Econ), Spec. in Ob/Gyn
Assist. Darko Siuka, MD, (UMC Ljubljana, Division of Internal Medicine, Japljeva 2, Ljubljana, Slovenia); Prof. Zvonka Zupanic Slavec, MD, PhD (University of Ljubljana, Faculty of Medicine, Institute for history of medicine, Zaloska 7a, Ljubljana, Slovenia)
University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia; UMC Ljubljana, Division of Ob/Gyn, Ljubljana, Slovenia
Rapid Response:
Covid-19: Vitamin D a risk-assessment tool and to reduce morbidity and mortality in covid-19 pandemic
Dear Editor,
NHS leaders in England have been advised to “risk-assess” and make “appropriate arrangements” to protect ethnic minority staff who may be at a greater risk of covid-19, as more than half of all deaths of healthcare workers were from an ethnic minority background. A national risk assessment framework would probably take into account ethnicity, age, sex, and other medical conditions, as well as nature of work, risk of exposure, and other factors. The steps to support BAME [black, Asian, and minority ethnic] staff would be developed (1). In our opinion, measuring vitamin D levels in individuals could be an important risk-assessment tool, and vitamin D supplementation might be a useful measure to reduce the risks in covid-19 pandemic.
It is well known that vitamin D reduces the risk of respiratory tract infections through several mechanisms. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza. Evidence supporting the role of vitamin D in reducing risk of covid-19 includes that the outbreak occurred in winter, a time when vitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration (2).
It is estimated that in overall, 13% of population across Europe has vitamin D deficiency (25(OH)D concentration <30 nmol/L) on average in the year, with differences in geographical regions and subpopulations (3). Recent statistical analysis of data obtained from hospitals and clinics across the world evaluated whether a link exists between severe cases of covid-19 that feature cytokine storm and vitamin D deficiency. Age-specific case fatality ratio (CFR) in Italy, Spain, and France (70 yrs ≤ age < 80 yrs) was substantially higher (>1.9 times) than in other countries (Germany, South Korea, China); for the elderly (age ≥70 yrs), Italy and Spain present the highest CFR (>1.7 times that of other countries). As more severe deficiency of vitamin D is reported in Italy and Spain compared to other countries the researchers conclude that elimination of severe vitamin D deficiency could reduce the risk of high CRP levels (4). Recent retrospective multicentre study of 212 cases with laboratory-confirmed infection with SARS-CoV-2 and known serum 25(OH)D levels revealed that serum 25(OH)D level was lowest in critical cases, but highest in mild cases. Vitamin D status was significantly associated with clinical outcomes: higher serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while lower serum 25(OH)D level could worsen clinical outcomes of covid-19 patients. In conclusion, vitamin D supplementation could possibly improve clinical outcomes of patients with covid-19 (5).
In addition to regional differences European data have confirmed, there are differences in vitamin D deficiency also regarding the ethnicity and race, as studies show that the prevalence of deficiency risk among Kurdish and Somali adults living in Finland is quite higher, 50.4% and 28.0% (3). The population survey in the United Kingdom found the prevalence of vitamin D deficiency was 20.0% in white, 40.0% in black and 63.8% in Asian participants(6). It can be assumed that skin colour (increased skin pigmentation inhibits cutaneous synthesis of cholecalciferol, the metabolic precursor of vitamin D), in addition to environmental and cultural factors in BAME subpopulation contribute to elevated risk for vitamin D deficiency, which could be related to higher covid-19 morbidity and mortality in BAME healthcare workers.
In Slovenia we have low covid-19 mortality rate, 47 per million population, compared to UK with 433 per million population.7 More than half of all deaths in Slovenia were from fragile elderly in nursing homes. One month ago, in spite of the fact that there are still no clear clinical data on the relation between vitamin D and covid-19, Slovenian medical community managed to agree to advice all medical doctors to supplement vitamin D in fragile patients in nursing homes, covid-19 patients in hospitals and healthcare workers, especially in covid-19 units. We believe that common sense approach in Slovenia regarding vitamin D supplementation was an important measure for low covid-19 morbidity and mortality in addition to other measures, e.g. social distancing and mandatory use of face masks in the community.
1. Iacobucci G. Covid-19: NHS bosses told to assess risk to ethnic minority staff who may be at greater risk BMJ 2020;369:m1820. doi: https://doi.org/10.1136/bmj.m1820
2. Grant WB, Lahore H, McDonnell SL, et a. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020;12:988. doi:10.3390/nu12040988
3. Cashman KD, Dowling KG, Skrabakova Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr 2016;103(4):1033–44.
4. Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv 2020.04.08.20058578; doi: https://doi.org/10.1101/2020.04.08.20058578
5. Alipio M. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with Coronavirus-2019 (Covid-2019) (April 9, 2020). https://ssrn.com/abstract=3571484 or http://dx.doi.org/10.2139/ssrn.3571484
6. O’Neill CM, Kazantzidis A, Kiely M, et al. A predictive model of serum 25-hydroxyvitamin D in UK white as well as black and Asian minority ethnic population groups for application in food fortification strategy development towards vitamin D deficiency prevention. J Steroid Biochem Mol Biol 2017;173:245–52.
7. Worldmeter. COVID-19 Coronavirus Pandemic. 5 May 2020. https://www.worldometers.info/coronavirus/
Competing interests: No competing interests