Here’s the study:

Castillo, Marta Entrenas, et al. “Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study.” The Journal of Steroid Biochemistry and Molecular Biology (2020): 105751.

This is a peer-reviewed, randomized, controlled study of hospitalized Covid-19 patients. So it is an “RCT”. [Correction: no placebo was used. The intervention group received calcifediol and the control group did not. Both groups received BAT, best available treatment.] This is the type of study that the press and various online critics demand. Some persons unwisely reject all other types of studies, which is not reasonable or scientific. But this is the type of study we’ve been waiting for, to confirm the other 20 studies here.

The study took place in a university hospital setting: Reina Sofia University Hospital, in Cordoba, Spain. The 76 patients were all hospitalized for confirmed cases of Covid-19. So these are not the mild to moderate, stay-at-home types of patients. The intervention group was 50 patients and the control group was 26 patients.

The intervention group received calcifediol, which is a type of vitamin D found in the blood. It is not the usual type of vitamin D found in supplements. Calcifediol is also known as 25(OH)D or 25-hydroxyvitamin D. The reason for giving this type of vitamin D is that the usual supplement type takes about 7 days to turn into calcifediol, so by giving patients calcifediol itself, you get the good effects without having to wait 7 or so days [per Wikipedia].

The dosage of calcifediol converts to IU (international units at a ratio of 200 to 1). So 10 micrograms of calcifediol is 2000 IU of vitamin D, whereas 10 micrograms of vitamin D3 is 400 IU (a 40:1 ratio). The dosage given to the patients, in IUs, was:

Day one: 106,400 IU of vitamin D
Day three: 53,200 IU
Day seven: 53,200 IU
Once-a-week thereafter: 53,200 IU

Yes, you can take your vitamin D supplement in a once-a-week dosage, instead of daily.

The results were astounding (and highly statistically significant). “Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%)”. Would you rather have a 50% risk of needing ICU care, or a 2% risk? Almost all hospitalized Covid-19 patients who die, die in the ICU. That is where the most severe cases are sent. So this study shows that vitamin D reduces the severity of Covid-19.

In the statistically adjusted results, vitamin D reduced the odds of ICU admission by 97%. The RR (risk reduction) for ICU admission in hospitalized Covid-19 patients was 0.03 as compared to the control, which is given the value of 1.00. The odds of Covid-19 patients in general, as compared to hospitalized Covid-19 patients, needing ICU care would be even lower, as you would first need to be hospitalized to enter that risk ratio, and vitamin D has been shown by other studies to reduce risk of hospitalization. So taking a vitamin D supplement has tremendous benefits.

For mortality, 2 patients in the control group died; no patients in the vitamin D group died. There were not enough deaths to make the results statistically significant. But hospitalized patients don’t usually die from Covid-19, unless they are in the ICU. We would expect the reduction in death to be of a similar order of magnitude to the reduction in need for ICU care. Also, if you need mechanical ventilation, that is ICU care. So the vitamin D would seem to reduce risk of ventilation as well.

There is now enough evidence for treatment with calcifediol, also known as 25(OH)D, to be STANDARD CARE for hospitalized patients with Covid-19. There is enough evidence for vitamin D supplementation to be recommended to everyone at risk of vitamin D, especially those at high risk. And since the elderly often have difficulty absorbing vitamin D, they should receive a higher dosage.

Here’s an article reviewing the study by Chris Masterjohn, Ph.D.: Finally Confirmed! Vitamin D Nearly Abolishes ICU Risk in COVID-19

Here’s a video on the study by Dr. Mobeen Syed (of DrBeen’s Medical Lectures)

More Studies

There are over 40 studies on Vitamin D and Covid-19, each showing a substantial benefit by reduction of risk: lower risk of contracting Covid-19, lower risk of having a severe case, lower risk of needing hospital admission or ICU admission or mechanical ventilation, and many showing lower risk of death from Covid-19. There is no other over-the-counter or prescription medication or supplement that has so many studies showing such a large benefit. And the risk of taking vitamin D, an essential nutrient, are very low, essentially nil.

How Much To Take

The medication in this study is the form of vitamin D that your body makes out of ordinary over-the-counter Vitamin D3, after it is processed by the liver. Almost all other studies used Vitamin D3 itself, with the many benefits discussed above. How much Vitamin D3 should you take?

If you have Covid-19, take 100,000 IU of vitamin D3 every day for 5 days. Then take either 10,000 IU of vitamin D3 daily OR 100,000 IU of vitamin D3 once a week (rather than daily). If you do not have Covid-19, just take the daily dose of 10,000 IU of vitamin D3 OR the weekly dose of 100,000 IU of vitamin D3.

Effect on the Pandemic

If every hospitalized Covid-19 patient were given calcifediol, the reduction in need for ICU beds and mechanical ventilation would be anticipated to be large. And since Covid-19 patients, if they are going to die from the disease, usually die in ICU, this should reduce deaths by at least half as well.

Having normal healthy blood levels of vitamin D reduces Covid-19 risks, including risk of infection [7, 8, 9, 11, 12, 14, 16, 23, 27, 32, 33, 37, 41], of having a severe case [1, 3, 4, 5, 15, 17, 20, 22, 24, 25, 26, 30, 34, 39, 40, 42, 43, 44, 45], of needing hospitalization, ICU care, and/or mechanical ventilation [2, 10, 14, 15, 21, 22, 24, 26, 30, 35, 40, 44], as well as the risk of dying from Covid-19 [4, 6, 7, 9, 12, 13, 17, 18, 19, 22, 24, 25, 31, 34, 36, 38, 40, 45, 46, 47, 48].

More Reading:
* List of Studies on Vitamin D and Covid-19
* The LongCovid Supplements List
* What Causes LongCovid also called Longhaulers Syndrome?
* Immune Privileged Cells affected by Longhaulers Syndrome
* The Longhaulers Hidden Virus Hypothesis

Ronald L. Conte Jr.
Covid.us.org
Follow Covid.us.org on Twitter
Note: The author of this article is not a doctor, nurse, or healthcare provider.

Vitamin D versus Covid-19, Studies

1. Alipio, Mark. “Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19).” SSRN 3571484 (9 April 2020).
Study Link | PDF Link

2. Lau, Frank H., et al. “Vitamin D insufficiency is prevalent in severe COVID-19.” medRxiv (28 April 2020).
Study Link | PDF Link

3. Daneshkhah, Ali, et al. “The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients.” medRxiv (2020).
Study Link | PDF Link

4. Davies, Gareth, Attila R. Garami, and Joanna C. Byers. “Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes.” medRxiv (2020).
Study Link | PDF Link

5. De Smet, Dieter, et al. “Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics.” medRxiv (2020).
Study Link | PDF Link

6. Raharusun, Prabowo, et al. “Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study.” (2020).
PDF file | PDF Link

7. Ilie, Petre Cristian, Simina Stefanescu, and Lee Smith. “The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.” Aging Clinical and Experimental Research (2020): 1.
Study Link | PDF Link

8. D’Avolio, Antonio, et al. “25-hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2.” Nutrients 12.5 (2020): 1359.
Study Link | PDF Link

9. Laird, E., et al. “Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.” Ir Med J; Vol 113; No. 5; P81: 2020.
PDF file | PDF Link

10. Faul, J.L., et al. “Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection.” Ir Med J; Vol 113; No. 5; P84: 2020.
PDF file | PDF Link

11. Meltzer, David O., et al. “Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence.” medRxiv (2020).
Study Link | PDF Link

12. Li, Yajia, et al. “Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States.” (2020).
PDF file | PDF Link

13. Pugach, Isaac Z. and Pugach, Sofya “Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe.” medRxiv (2020).
Study Link | PDF Link

14. Merzon, Eugene, et al. “Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study.” medRxiv (2020). — Low vitamin D increased risk (adjusted OR) of infection with Covid-19 by 45% and of hospitalization for Covid by 95%.
Study Link | PDF Link

15. Panagiotou, Grigorios et al., “Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.” medRxiv (2020). Conclusion: “we found that patients requiring ITU admission [in the ICU] were more frequently vitamin D deficient than those managed on medical wards [on the floor], despite being significantly younger.”
PDF file Link | PDF Link

16. Chang, Timothy S., et al. “Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System.” medRxiv (2020).
Study Link | PDF Link
~ Risk factors included vitamin D deficiency, which increased risk of COVID-19 diagnosis by 80% (OR 1.8 [1.4-2.2], p=5.7 x 10-6).

17. Maghbooli, Zhila, et al. “Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients.” Available at SSRN 3616008 (2020).
Study Link | PDF Link
~ Vitamin D sufficiency reduced clinical severity and inpatient mortality.
* See this Expression of Concern by the editors of PLoS One

18. Panarese and Shahini, “Letter: Covid-19 and Vitamin D” Alimentary Pharmacology and Therapeutics, April 12, 2020.
Link to Letter | PDF Link
~ Covid-19 mortality increases with increasing latitude (by nation), and vitamin D blood levels decrease with increasing latitude. The authors propose that low levels of vitamin D increase Covid-19 mortality.

19. Carpagnano, Giovanna Elisiana, et al. “Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19.” Journal of Endocrinological Investigation (2020): 1-7. Study Link | PDF Link
~ “A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D = 10 ng/mL had a 5% mortality risk (p = 0.019).”

20. Mardani, R., et al. “Association of vitamin D with the modulation of the disease severity in COVID-19.” Virus Research (2020): 198148. Study Link | PDF Link

21. Castillo, Marta Entrenas, et al. “Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study.” The Journal of Steroid Biochemistry and Molecular Biology (2020): 105751. Study Link | PDF Link

22. Radujkovic, et al. “Vitamin D Deficiency and Outcome of COVID-19 Patients.” Nutrients 2020, 12(9), 2757; Study Link | PDF Link
— “The present study demonstrates an association between VitD deficiency and severity of COVID-19.
VitD-deficient patients had a higher hospitalization rate and required more (intensive) oxygen therapy
and IMV. In our patients, when adjusted for age, gender, and comorbidities, VitD deficiency was
associated with a 6-fold higher hazard of severe course of disease and a ~15-fold higher risk of death.”

23. Israel, Ariel, et al. “The link between vitamin D deficiency and Covid-19 in a large population.” MedRxiv 9/7/2020. Study Link | PDF Link

24. Jae Hyoung Im, et al. “Nutritional status of patients with coronavirus disease 2019 (COVID-19).”
International Journal of Infectious Diseases. August 7, 2020. PDF Link | PDF Link

25. Gennari L, et al “Vitamin D deficiency is independently associated with COVID-19 severity and mortality” ASBMR 2020; Abstract 1023. Study Link | PDF Link

26. Baktash, Vadir, et al. “Vitamin D status and outcomes for hospitalised older patients with COVID-19.” Postgraduate Medical Journal (2020). Study Link | PDF Link
— “The main findings of our study suggest that older patients with lower serum concentrations of 25(OH)D, when compared with aged-matched vitamin D-replete patients, may demonstrate worse outcomes from COVID-19. Markers of cytokine release syndrome were raised in these patients and they were more likely to become hypoxic and require ventilatory support in HDU.” [HDU is high dependency unit]

27. Kaufman HW, et al. “SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.” (2020) PLoS ONE 15(9): e0239252. Study Link | PDF Link
— Optimum vitamin D blood level for reducing Covid-19 infection was found to be in the 50’s (ng/ml). This is the first study to show that 25(OH)D at levels above 30 have additional benefits.

28. Brenner, Hermann, Bernd Holleczek, and Ben Schöttker. “Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?.” Nutrients 12.8 (2020): 2488. PDF Link
— “Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.”

29. Pepkowitz, Samuel H., et al. “Vitamin D Deficiency is Associated with Increased COVID-19 Severity: Prospective Screening of At-Risk Groups is Medically Indicated.” (2020). PDF File
— Persons hospitalized for Covid-19 were more than twice as likely to need ICU care if they had with vitamin D deficiency.

30. Mandal, Amit KJ, et al. “Vitamin D status may indeed be a prognosticator for morbidity and mortality in patients with COVID‐19.” Journal of Medical Virology. PDF Link
— Findings: “patients with low concentrations of 25OH-D (<or=30nmol/l) demonstrated clinically relevant, elevated markers of cytokine release syndrome and were more likely to become hypoxic and require ventilatory support."

31. Karahan and Katkat. “Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey.” The journal of nutrition, health & aging (2020). PDF File

32. Faniyi, et al. “Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.” medRxiv 6 Oct. 2020. PDF Link
— “Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff.”

33. Yılmaz, Kamil, and Velat Şen. “Is Vitamin D Deficiency a Risk Factor for Covid 19 in Children?.” Pediatric Pulmonology. Study Link
— “The symptom of fever was significantly higher in COVID‐ 19 patients who had deficient and insufficient vitamin D levels than in patients who had sufficient vitamin D level.”
— “Patients with COVID‐19 had significantly lower vitamin D levels 13.14 ng/ml than did the controls 34.81 ng/ml.”

34. Annweiler, C. et al. “Vitamin D and survival in COVID-19 patients: A quasi-experimental study.” The Journal of Steroid Biochemistry and Molecular Biology, 13 October 2020. Study Link
— Bolus vitamin D3 supplementation during or just before COVID-19 was associated with less severe COVID-19 and better survival rate in frail elderly.

35. Han, Jenny E., et al. “High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial.” Journal of clinical & translational endocrinology 4 (2016): 59-65. Study Link
— Hospital stay cut in half for patients needing ICU care and ventilation and receiving 100,000 IU Vitamin D3 daily for 5 days. Note that this was not a Covid-19 specific study, but a study of ICU patients on mechanical ventilation.

36. De Smet, Dieter, et al. “Serum 25 (OH) D Level on Hospital Admission Associated With COVID-19 Stage and Mortality.” American journal of clinical pathology (2020). Study Link
— Covid-19 patients admitted to hospital were 3.87 times more likely to die from Covid-19, if they had vitamin D deficiency.

37. Rastogi, Ashu, et al. “Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).” Postgraduate medical journal (2020). Study Link
— Covid-19 patients were given 60,000 IU vitamin D daily for 7 days; these patients were 3.0 times more likely to become negative for Covid-19 than patients not given vitamin D.

38. Afshar, Parviz, Mohammad Ghaffaripour, and Hamid Sajjadi. “Suggested role of Vitamin D supplementation in COVID-19 severity.” Journal of Contemporary Medical Sciences 6.4 (2020). Study Link
— 300,000 IU vitamin D3 once, then 100 IU per kilogram of body weight per day; greatly reduced deaths and length of hospital stay for Covid-19.

39. Luo, Xia, et al. “Vitamin D Deficiency Is Inversely Associated with COVID-19 Incidence and Disease Severity in Chinese People.” The Journal of Nutrition (2020). Study Link
— vitamin D deficiency (<30 nmol/L) (OR: 2.72) was significantly associated with COVID-19 severity.

40. Pereira, Marcos, et al. “Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis.” Critical reviews in food science and nutrition (2020): 1-9. Study Link
— severe cases of COVID-19 present 64% more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization and mortality from COVID-19. We observed a positive association between vitamin D deficiency and the severity of the disease.

41. Katz, Joseph, Sijia Yue, and Wei Xue. “Increased risk for Covid-19 in patients with Vitamin D deficiency.” Nutrition (2020): 111106. Study Link
— “patients with vitamin D deficiency were 5 times more likely to be infected with Covid-19 than patients with no deficiency after adjusting for age groups”

42. Arvinte, Cristian, Maharaj Singh, and Paul E. Marik. “Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study.” Medicine in drug discovery 8 (2020): 100064. Study Link
— “Serum levels of vitamin C and vitamin D were low in most of our critically ill COVID-19 ICU patients.”

43. Yılmaz, Kamil, and Velat Şen. “Is vitamin D deficiency a risk factor for COVID‐19 in children?.” Pediatric Pulmonology 55.12 (2020): 3595-3601. Study Link | Explanation of Study
— Children in this study with higher vitamin D blood levels (20 ng/ml or higher) were 4.6 times more likely to have no symptoms while infected with Covid-19, and 72% less likely to have a moderate/severe case of Covid-19 than children with vitamin D deficiency.

44. Tan, Chuen Wen, et al. “A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.” medRxiv (2020). Study Link
— “a vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both.”

45. Jain, Anshul, et al. “Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers.” Scientific reports 10.1 (2020): 1-8. Study Link
— “The fatality rate was high in vitamin D deficient (21% vs 3.1%). Vitamin D level is markedly low in severe COVID-19 patients.” In this study, patients with low vitamin D had a mortality rate of 21%; those with higher vitamin D had a mortality rate of only 3.1%. Those with higher vitamin D were more likely to have a mild case, and less likely to die; those with low vitamin D were more likely to have a severe case, and more likely to die.

46. Ling, Stephanie F., et al. “High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.” Nutrients 12.12 (2020): 3799. Study Link
— “In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19.” In one group, the reduction in risk of death was 87%; in the other group, the reduction was 62%.

The evidence is overwhelming. Persons with Covid-19 should be given high-doses of Vitamin D3 (called “Cholecalciferol”) to reduce risk of death. Many other studies (above) showed similar results.

47. Vassiliou, Alice G., et al. “Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort.” Nutrients 12.12 (2020): 3773. Study Link
— “All patients who died within 28 days belonged to the low vitamin D group…. Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors.”

48. Anjum, S., et al. “Examine the association between severe Vitamin D deficiency and mortality in patients with Covid-19.” Pakistan Journal of Medical and Health Sciences (2020): 1184-1186. Study Link
— “Patients with severe vitamin D deficiency had high rate of mortality (26.67%) as compared to patients with no vitamin D deficiency (7.5%)”