Last update 2022-04-19.
To make suggestions and changes see the Github repo: Vitamin_d_covid.
For more on vitamin D and Covid, see my
blog. Note that as of fall 2021, I am no longer tracking
retrospective studies.
Direct research on vitamin D and Covid
Supplementation studies
Randomized
Supports link to vitamin D
- A parallel
pilot randomized open label trial of 76 patients in Spain found that
the administration of calcifediol reduced ICU admission and mortality.
Of the 50 patients treated with 1000 ug of calcifediol. 13/26 patients
in the control group required ICU care compared with 1 in the
intervention group. A subsequent
statistical analysis showed that decreased ICU admissions were not
due to uneven distribution of comorbidities or other prognostic
indicators, to imperfect blinding, or to chance, but were instead
associated with the calcifediol intervention. (Castillo et all, August
2020)
- A randomized, placebo
controlled trial found that therapeutic, high-dose cholecalciferol
supplementation led to SARS-CoV-2 RNA negative status in additional
41.7% of mildly symptomatic Covid patients (p<0.001) and was useful
for viral SARS-CoV-2 RNA clearance.
- A randomized open-label
trial of 87 vitamin D deficient Covid patients found that
supplementation of 60,000 IU/day for 8-10 days reduced inflammatory
biomarkers including CRP and IL-6. (Lakkireddy et al, 2021)
- A randomized open-label trial of
69 hospitalized patients found that those who received 5,000 IU of
vitamin D daily recovered from cough and ageusia more quickly than those
who received 1,000 IU. This study seems to suffer from the multiple
testing problem and its conclusions should be treated with a grain of
salt. (Sabico
et al, August 2021)
- A randomized controlled open-label
trial of 50 hospitalized Covid patients found that calcitriol
supplementation improved the respiratory status (SpO2/FIO2) of treated
patients. (Elamir et al, September 2021)
- A randomized, blinded, placebo
controlled trial (n = 106) found that patients treated with low dose
calcifediol (25 ug) had a better neutrophile to lymphocyte ration than
controls. The trial did not detect a significant difference in
mortality, ICU admission, or length of hospital stay. (Maghbooli
et al, October 2021)
- A randomized, blinded, placebo
controlled trial (n = 198) of health care workers in Mexico city
found that vitamin D supplementation reduced Covid-19 infection. The
relative risk was 0.23 with a CI between 0.09–0.55. (Keever et al, April
2022)
Does not support vitamin D link
- A randomized, placebo controlled trial
of 240 patients found that a one-time supplementation of 200,000 IU of
vitamin D, on average 10 days after symptom onset did not reduce the
length of hospital stay in severe Covid-19 patients. The treatment was
safe and well tolerated.
- A study of
175 ICU patients found that high-dose paraternal vitamin D did not
reduce the need for mechanical ventilation or death. Note that vitamin D
was administered after ICU admission. (Güven and Gültekin, July
2021)
- A study
of 170 outpatients found that calcifediol supplementation did not
improve symptom resolution. Note that vitamin D levels in the placebo
arm were high (37 ng/ml at baseline). (Bishop et al, February 2022)
- A RCT
of 6200 people found that vitamin D supplementation of 3,200 IU/day
did not reduce Covid-19 infection or severity as compared with 800
IU/day or no-offer groups. There was a very high vaccination rate in all
arms of the trial which may have overwhelmed any potential treatment
effect. (Jolliffe et al, March 2022)
Non-Randomized
Supports vitamin D
- A ward
randomized trial of 984 patients found that those supplemented with
calcifediol had a lower ICU admissions rate and mortality rate than the
control wards. (Nogues et all, June 2021)
- A large
propensity score matched study of 16,000 patients found that
calcifediol and cholecalciferol supplementation were associated with
large reductions in Covid–19 mortality. (Loucera et al, April 2021)
- A cohort
study of 574 patients in Spain found that calcifediol
supplementation was associated with a significant decrease in
in-hospital mortality with an adjusted odds ratio of 0.16. (Alcala-Diaz et al, May
2021)
- A small
cohort trial found that just 16% of patients who received vitamin D,
magnesium, and vitamin B12 required oxygen compared with 61.5% of the
previous cohort who did not receive DBM supplementation. (Chuen Wen Tan,
October 2020)
- A retrospective
study found that hospitalized patients who were treated with vitamin
D were less likely to die than those who did not receive vitamin D.
(Ling et all, October 2020)
- A
retrospective study found that French nursing home residents who had
recently received a bolus dose of vitamin D were more likely to survive
a Covid-19 infection than residents who had not recently received a
supplement. 92% of the 57 people who received vitamin D survived, while
66% of the 9 people in the cooperator group survived. (Anweller et. al,
October 2020)
- A retrospective
study found that regular bolus vitamin D supplementation was
associated with less severe COVID-19 and better survival in frail
elderly. (Anweller et. al, November 2020)
- A follow-up
study found that geriatric Covid patients who received regular
vitamin D supplementation prior to infection were less likely to
experience severe disease or to die than patients who either were not
supplemented, or were supplemented after infection. ((Anweller et. al,
July 2021)
- A multi-center
observational study of 1,000 hospitalized Covid patients found that
Cholecalciferol supplementation was associated with lower mortality.
(Ling et al, December 2020)
- An observational
study of Italian nursing home residents found that vitamin D was
associated with a lower risk of dying. The authors note that “\[in\] the absence of contraindications …
the administration of cholecalciferol in older subjects could be
strongly advocated.” (Cangiano et al, December 2020)
- A retrospective
Catalonian study found that patients with chronic kidney disease who
were treated with calcitriol were less likely to develop severe Covid or
die than matched controls. (Oristrell et al, April 2021)
- A large restrospective
cohort study of Spanish Covid patients found that patients who had
taken calcifediol or cholecalciferol had better who achieved serum
levels greater than 30 ng/ml had better Covid outcomes than propensity
matched controls. (Oristrell et al, July 2021)
- A Turkish
study found that hospitalized vitamin D deficient patients who were
supplemented with 300,000 IU of vitamin D had a lower mortality rate
than controls. (Yidiz et al, September 2021)
- A cohort
study of 16,000 Spanish Covid patients found that patients who had
received vitamin D perscriptions prior to Covid hospitalization were
less likely to die than those who hadn’t received a perscription The
effect was larger for patients perscribed calcifediol, and for those
whose perscription was closer to the date of hospitalization. (Loucera
et al, December 2021)
Does not support vitamin D
- A cohort
study of 163 turkish patients found that a 300,000 IU of vitamin D
administered to severely ill patients in the ICU found that while
patients treated with vitamin D had a lower rate of mortality and
intubation, this difference was not significant. (Güven
and Gültekin,
September 2021)
Covid severity associated with serum vitamin D levels
Pre-infection blood samples (Out of date)
Supports link to vitamin D
- A retrospective
cohort study found that Chicago patients who were likely vitamin D
deficient were more likely to test positive for Covid-19. (Meltzer et
al, May 2020)
- An Israeli
study of 7,000 patients with pre-Covid serum vitamin D tests found
that vitamin D levels were associated with Covid infection and
hospitalization. (Eugene Merzon et al, July 2020)
- An analysis
of Israeli vitamin D tests performed between 2010 and 2019 found that
vitamin D deficiency predicted Covid-19 infection. (Israel et al, August
2020)
- An
analysis of 190,000 patients found that the probability of testing
positive was associated with vitamin D levels. This association held
across all age groups, ethnicities and geographies. (Kaufman et all,
Sept 2020)
- A study
of 437 New York Covid patients found that vitamin D levels measured
up to three months prior to Covid were associated with need for
supplemental oxygen, but not hospitalization or death. (Gavioli et al,
February 2021)
- A cohort
study of 4638 patients in Chicago found that vitamin D levels taken
within the past year were associated with Covid positivity for Black
patients, but not white patients. (Meltzer et al, March 2022)
- A retrospective
study of 1176 Israeli patients found that pre-infection vitamin D
levels were associated with disease severity and mortality. (Dror et al,
June 2021)
- A retrospective
study of 80,670 patients found that pre-infection vitamin D
deficiency was associated with a higher rate of hospitalizations. (Jude
et al, June 2021)
- A prospective
observational study found that Black women with vitamin D deficiency
were more likely to test positive than women without vitamin D
deficiency. (Cozier et. al, July 2021)
- An Israeli
study found that vitamin D deficient people were 14x more likely to
contract severe Covid than people with high levels of vitamin D. (Dror
et al, February 2022)
Does not support vitamin D link
Vitamin D levels between 2006-2010 were
associated with Covid-19 mortality, but not after controlling for
other variables in the data set. It’s hard to make inferences from 10
year old blood samples because there’s a causal story in which low
vitamin D in 2010 increases vitamin D in 2020 because that
group is likely to supplement. (Hastie et al, July 2020)
- A subsequent
analysis of the same dataset concluded that habitual vitamin D
supplementation led to reduced Covid severity after controlling for
factors like race, income, and comorbidities. (Ma et all, January
2021)
Post-infection blood samples (Out of date)
Supports vitamin D link
- A re-analysis of 107 Swiss blood
samples found that PCR positive patients had 25-hydroxyvitamin D
concentrations half that of PCR negatives. This finding held after
stratifying for age and gender. (Avolio et 1) l, April 2020)
- Hospitalized male Covid-19 patients were
found to have lower vitamin D levels than controls. (De Smet et al,
May 2019)
- A observational study
from Belgium found that vitamin D deficiency is correlated with the
risk for hospitalization for COVID-19 pneumonia and predisposes to more
advanced radiological disease stages. (De Smet, November 2020)
- Vitamin D deficiency was
more common among ITU Covid patients than the general population in
a Newcastle hospital. (Panagiotou et all, June 2020)
- A Mexican
study found that patients with vitamin D serum levels bellow 8 ng/mL
had 3.68 higher risk of dying from COVID-19. (Arturo Rodríguez Tort et
al, April 2020)
- A Iranian
study (Maghbooli et al, September 2020) found there was a
significant association between vitamin D sufficiency and reduction in
clinical severity. Note that an expression
of concern was filed for this publication.
- A study
of 42 COVID-19 patients in a respiratory ICU found that 50% of vitamin D
deficient patients died after 10 days compared with 5% of non-deficient
patients. (Carpagnano et all, August 2020)
- A prospective
cohort study found that vitamin D deficiency was more common among
Covid positive patients presenting with Covid symptoms than Covid
negative patients, and suggested that it could be considered as a
diagnostic tool. (Baktash V et all, August 2020)
- A
study of patients presenting with Covid symptoms at an Iranian
hospital found that vitamin D deficiency and ACE dysregulation were more
common among those who tested positive for Covid-19. (Mardenia et all,
August 2020)
- A German
Study found that vitamin D status was associated with need for
mechanical ventilation and death. (Radujkovic et al, August 2020)
- A
small prospective cohort study of older adults found that vitamin D
deficiency was associated with mechanical ventilation, but not death.
(Baktash et all, September 2020)
- A
Turkish study found that vitamin D deficiency was associated with
mortality. (Karahan & Katkat October 2020)
- A
study of UK health professionals found that vitamin D deficient
individuals were more likely to be seropositive for Covid antibodies.
(Aduragbemi et all, October 2020)
- A study of Covid
positive children found that children with Covid had lower vitamin D
levels than healthy controls. (Yilmaz & Sen, October 2020)
- A case
control study in China found that vitamin D deficiency was higher in
Covid patients than healthy controls, and that it was associated with
disease severity. (Ye et. al, October, 2020)
- A retrospective case
control study of 216 hospitalized patients found that 80% of Covid
patients were vitamin D deficient, while just 42% of matched controls
were deficient. The study did not find that vitamin D deficiency was
associated with disease outcome. (Hernández et al, October 2020)
- A study
of 74 hospitalized patients found that vitamin D deficiency was
associated with Covid lung involvement, and mortality. (Abrishami et
all, October 2020)
- A prospective
observational study found that criticlaly ill Covid patients had
higher rates of vitamin D deficiency than asymptomatic patients. (Jain
et al, November 2020)
- A prospective
observational study of 30 Greek ICU patients found that vitamin D
deficiency was associated with mortality. All of the patients who died
had vitamin D levels below the median of 15.2 ng/mL. (Vassiliou et al,
January 2021)
- A retrospective
study of 508 Iranian patients found that serum vitamin D and
supplementation history was associated with better Covid disease
progression. (Vasheghani et al, January 2021)
- An observational
study of 330 hospitalized Armenian Covid patients found that
hospitalized patients had lower vitamin D than healthy controls. 45% of
patients had bloog levels below 12 nm/ml which the author’s note is “a
threshold value acknowledged by all authoritative bodies to be
associated with frank, unequivocal vitamin D deficiency.” (Hutchings et
all, January 2021)
- A multicenter observational
study of 144 hospitalized patients found that serum vitamin D levels
were associated with in-hospital mortality and need for mechanical
ventilation. (Angelidi et al, January 2021)
- A cohort
study of 487 patients found that vitamin D deficiency was associated
with PCR positivity, d-dimer status, CRP, and the number of affected
lung segments in COVID‐19 positive patients. (Demir, Demir, Aygun,
January 2021)
- An observational
study of 64 elderly Covid patients found that they had lower vitamin
D levels than matched controls. The median vitamin D level amond Covid
patients was 7.9 ng/ml which is profoundly low. (Sulli et al, February
2021)
- A study of 52
Covid patients found that 80% of them were vitamin D deficient and
that vitamin D levels were correlated with various biomarkers of disease
activity. (Ricci et al, March 2021)
- A study of 348
Italian Covid patients found that vitamin D deficiency and secondary
hyperparathyroidism were associated with worse Covid outcomes. The
median vitamin D level was 12.1 ng/mL. (Mazziotti et al, March
2021)
- A chart review study
of 287 hospitalized patients found that vitamin D sufficiency
reduced the risk of Covid related mortality.
- A Mexican
study of 551 hospitalized patients found that low vitamin D levels
were present in 45% of them, and was associated with an increased
mortality risk. (Vanegas-Cedillo et al, March 2021)
- A retrospective study of 464 patients in the UAE found that vitamin
D levels below 12 ng/ml were associated with disease severity and death.
(AlSafar et al, May 2021)
Does not support link to vitamin D
- A small
trial did not find an association between vitamin D deficiency and
Covid-19 severity. The study did find an association among younger
patients. (Macaya et. al, September 2020)
- A case-control
study did not find that Covid positive patients had lower vitamin D
levels than patients hospitalized with non-Covid pneumonia or a set of
non-respiratory conditions. The comparator groups in this study are a
bit strange because low vitamin D levels are implicated in almost all of
the diagnoses included in this study. See the comments associated with
the paper. (Tomasti et al, October 2020)
- An Italian
study of 347 patients did not find that hospitalized Covid patients
had lower serum vitamin D than non-Covid patients. The authors note that
“Because a large portion of patients were below the suggested 30 ng/mL
threshold, we can’t exclude that VitD supplementation, restoring normal
levels, might be beneficial in reducing the risk of infection.” (Ferrari
& Locatelli, November 2020)
- A study
of 135 hospitalized patients in the Netherlands was not assoicated with
need for mechanical ventilation or death. The author’s note that vitamin
K may be an important factor along with vitamin D. (Walk et al, November
2020)
- An Indian
study found that there was no difference in clinical outcome between
vitamin D sufficient individuals ( > 30 nmol/L) and insufficient
individuals. (Jevalikar et al, December 2020)
- A
study of 400 hospitalized patients found no association between
vitamin D levels and Covid outcomes. However, pre-admission
supplementation habits were not measured and the vitamin D replete group
were significantly older and had more comorbidities than the vitamin D
deficient group. (Jevalikar et all, March 2021)
In vitro evidence (Out of date)
- Calcitriol, the active form of Vitamin D is
active against the SARS-COV2 virus. (Chee Keng Mok et al, June
2020)
- An in vitro study
found that the antimicrobial peptide LL-37, which is upregulated by
vitamin D, binds to the SARS-COV2 spike protein. The study “supports the
prophylactic use of vitamin D to induce LL-37 that protects from
SARS-CoV-2 infection, and the therapeutic administration of vitamin D
for the treatment of COVID-19 patients”. (Roth et al, November
2020)
- Vitamin
D derivatives can inhibit parts of the SARS-COV2 viral life-cycle.
(Qayyum et al, July 2021).
Non-clinical causal data (Out of date)
Supports vitamin D
- Evidence supports a vitamin-D
causal model more than an acausal one. (Davies et al, June 13
2020)
- A Mendelian
randomisation analysis of excess COVID-19 mortality of
African-Americans in the US suggests that vitamin D is a risk factor for
Covid Mortality. (Martin Kohlmeier, May 2020)
Does not support vitamin D
- A Mendelian
randomization using genes associated with vitamin D deficiency did
not support a causal connection between vitamin D and Covid-19
mortality. It appears that this study used UK Biobank data, but the date
of the samples were not disclosed. (Liu et al, August 2020)
- Another Mendelian
randomization based on UK biobank and other genetic datasets found
that people of European descent who were genetically predisposed to high
vitamin D levels did not change their risk of contracting Covid, but
seemed to increase their risk of hospitalization. (Butler-Laporte,
September 2020)
Ecological studies (Out of date)
- A study out of Northwestern
University found that the vitamin D status of a country’s elderly
population was associated with the number of severe cases of Covid-19 in
that country. (Daneshkhah1 et al, April 2020)
- There was a strong
correlation between vitamin D levels and European mortality which
increased over time. (Chuen Wen Tan, June 2020)
- UVB radiation, which the skin uses to manufacture vitamin D is associated
with lower death rates and case fatality rates. (Moozhipurath et al, May
1st 2020)
- Covid-19 deaths-per-million appears to vary by
latitude. (Rhodes et al, June 2020)
- Latitude was not
associated with a proportional increase in cases during one week of
March. (Jüni et al, June 2020)
- Latitude is a significant predictor of Covid mortality after controlling for
age. (Rhodes et al, July 2020)
- Vitamin D levels were inversely
associated with cases per million in Europe, but not with deaths per
million. (Sing, Kaur, Kumar Sigh, August 2020)
- The fall 2020 outbreaks in Europe appear
to be correlated with latitude but not temperature. (Warland,
November 2020)
Vitamin D background and previous studies (Out of date)
Clinical guidance (Out of date)
Supports supplementation
- The Frontline Covid-19 Critical Care Alliance recommends vitamin D as a
Covid-19 therapeutic for inpatient, outpatient, and prophylactic
use.
- Israel
started recommending vitamin D in October 2020.
- Slovenia
has begun administering vitamin D to residents of nursing homes and
health care workers.
- The French National Academy of Medicine recommends
that people over 60 be tested for vitamin D deficiency and given a bolus
dose of 50,000 to 100,000 IU. It further recommends that all Covid
positive patients take 800 to 1000 IU a day upon diagnosis.
- A Swiss expert panel recommends
that people supplement with 2,000 IU of vitamin D per day.
- New Zealand provides
50,000 IU monthly vitamin D supplementation to all aged care
residents.
- The Scottish government will
provide vulnerable populations with vitamin D supplementats.
Does not support supplementation
- NICE, an English clinical research group, does not
recommend vitamin D supplementation. (Nice.org.u, June 29 2020)
Lit reviews and clinical guidance
If you only have time for one review
Other reviews
- A
Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity
Is Increased in Vitamin D Deficiency note that this review only
included studies which were available prior to July 2020, so did not
include the COVIDIOL pilot RCT. (Benskin, Sept 2020)
- This
review of potential vitamin D mechanisms of action provides some
useful history on the origin of vitamin D dosing recommendations. They
also review their clinical guidelines after treating several thousand
patients with 5000-10000 IU/day, including recognizing and resolving
hypercalcemia or other adverse events. (McCullough, May 15 2020)
- A review
in Nature suggests that all patients should be monitored and
potentially treated for vitamin D deficiency. (Ebadi et al, May
2020)
- A bmj report
which is generally critical of the connection between Covid-19 and
vitamin D nevertheless concludes that supplementation according to
government health guidelines (no more than 4,000 IU/day) is sensible for
most people. (Lanham-new, May 2020)
- A quarantine hospital in Egypt has started
providing (Egypt Today, News source, June 1st 2020) vitamin D to
fronting medical workers.
- A review
of the evidence finds that supplementing with vitamin D in
accordance with government guidelines is a good idea, but there is no
evidence to support supplementation rates higher than 4,000 IU/day.
(Lanham-New et al, April 2020)
- a Commentary
in Metabolism Journal calling for action to eliminate Vitamin D
deficiencies, and recommending a higher Vitamin D advice during the
pandemic of 1000-2000 IU a day. (Manson et al, July 23, 2020)
- MECHANISMS IN
ENDOCRINOLOGY: Vitamin D and COVID-19. (Bilezikan et al, March
2021)
- Vitamin
D and Immune Regulation: Antibacterial, Antiviral,
Anti‐Inflammatory. (Bishop et al, March 2021)
- Relationships
between hyperinsulinaemia, magnesium, vitamin D, thrombosis and
COVID-19: rationale for clinical management. (Cooper et al, March
2021)