Vitamin D and survival in COVID-19 patients: A quasi-experimental study
Journal of Steroid Biochemistry and Molecular Biology, Oct 2020 https://doi.org/10.1016/j.jsbmb.2020.105771
Cedric Annweiler, B erangere Hanotte, Claire Grandin de l,Eprevier, Jean-Marc Sabatier, Ludovic Lafaie, Thomas Celarier
VitaminDWiki summary and comment
Residents were routinely given a single dose of 80,000 IU of Vitamin D every 2-3 months
Then COVID-19 struck this nursing home in France
A small Vitamin D single dose raises the vitamin D levels for about a month
80K IU Vitamin D given once every 80 days is far better than 1,000 IU given daily
Vitamin D – individual responses to 100,000 IU – March 2017 has the following
Note: The response is an average - half of the people have smaller responses
Vitamin D levels - before and 4 weeks after 100,000 IU
52% achieved levels > 30 ng; approximate 20 ng increase - with lots of variability
- - - - - - - - - - - - - - - -
At this time it appears that 50,000 IU taken daily for a week,
followed by 50,000 every 2 weeks will be enough to COVID-19
*Will know if this is correct during 2021, when the Clinical trials listed at the bottom of this page have been completed
- One pill every two weeks gives you all the vitamin D most adults need
- 50,000 IU every two weeks proven by RCT to prevent or treat 25 health problems as of Oct 2018
- Influenza prevented by 40 ng levels or treated with vitamin D hammer (50,000 IU) – June 2015
- Hill's Criteria indicates that COVID-19 will be treated by Vitamin D - Annweiler June 8 2020
- Need 40 to 60 ng of Vitamin D – 48 scientists call for action – 2015 Dr. Annweiler was one of them
- Nursing homes could reduce risk of COVID-19 with Vitamin D – June 30, 2020
Items in both categories Virus and Mortality are listed here:
- Excess Deaths in Australia jumped up in 2022– preprint Feb 2023
- Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
- Number needed to vaccinate to prevent 1 Omicron death: 30,000 for age 60-70 - Sept 2022
- COVID survival in Europe in 2020 best predicted by population-level Vitamin D (of 13 variables) – July 2022
- Elderly who had been in COVID ICU were 4X more likely to die if low vitamin D – Nov 2022
- More COVID mortality if less than 20 ng of Vitamin D (Mexico) – May 2022
- 15,000,000 excess deaths in 2 years - May 2022
- COVID death 5.2X more likely if Vitamin D deficient – May 2022
- 29 X more likely to die of COVID if less than 20 ng of Vitamin D - March 2022
- Giving Vitamin D reduced COVID Mortality– Review of 11 studies – March 2022
- 18 million excess global deaths in past 2 years: COVID plus collateral damage - Lancet March 2022
- COVID severity and death more likely if low vitamin D (Egypt this time) - March 2022
- US nursing homes are epicenters for COVID deaths (200,000) - Feb 2022
- Ivermectin taken before COVID decreased death rate by 68 percent (3,000 with Ivermectin vs 3,000 without) - Dec 24, 2021
- Increase in non-COVID deaths (ages 18-64) in Indiana, India, etc. - Jan 5, 2022
- Only 35,000 died in US of COVID who previously had been healthy
- COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021
- COVID-19 patients getting 300,000 IU of Vitamin D were 5X less likely to die – Sept 2021
- Predict 2X more likely to die of COVID-19 if vitamin D Deficient (Iran 2020) – Sept 2021
- COVID-19 mortality not associated with Vitamin D (everyone had very low levels) -Sept 2021
- COVID-19 mortality for Blacks is 5X that for whites in 2 LA Hospitals - July 2021
- COVID-19 mortality was associated with vitamin D deficiency of 47 countries – July 2021
- Similar death rate for Vaccination and COVID-19 study and video – June 24, 2021
- COVID-19 death in hospital 5X more likely if low vs high vitamin D – preprint June 2021
- COVID-19 deaths 1.7X more likely if low vitamin D (even after “adjusting” for low D health problems) – May 2021
- COVID-19 deaths 1.5X less likely if more than 40 ng of vitamin D – US VA – April 2021
- Vitamin D supplementation and high levels reduce COVID-19 deaths in elderly – Review April 17, 2021
- Less COVID-19 infection, mortality in countries with higher Vitamin D (Asia in this case) – May 2021
- COVID-19 was the third-leading cause of death in the US, especially in those with dark skins - April 1, 2021
- Risk of COVID-19 death was 4.9 X higher if very low vitamin D – March 31, 2021
- COVID-19 mortality 2X higher if low Vitamin D (Mexican hospital, preprint) - March 2021
- All COVID-19 patients had low vitamin D, the lowest were more likely to die – Feb 18, 2021
- 2.7 fewer COVID-19 hospital deaths in those having more than 30 ng of vitamin D – Mayo Jan 9, 2021
- Worse COVID-19 patients got 400,000 IU of vitamin D, deaths cut in half – Jan 14, 2021
- Iranians with COVID-19 were 2.3 X more likely to die if low vitamin D – Jan 2021
- Poor COVID-19 prognosis was 6 X more likely if low vitamin D – Jan 21, 2021
- Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
- 2.8 X fewer COVID-19 nursing home deaths if add 10,000 IU Vitamin D daily for a week (small observation)- Jan 2021
- Italian nursing home COVID-19 – 4X less likely to die if taking Vitamin D– Dec 22, 2020
- Shift workers 2X more likely to get COVID-19 (low Vitamin D) - Dec 2020
- Those getting high dose vitamin D were 7 X less likely to die of COVID-19 - Dec 11, 2020
- COVID-19 male mortality increased 3.9 X if low vitamin D – observation Nov 25, 2020
- Hospital COVID-19 observation: 7X more likely to live if more than 20 ng of vitamin D– Nov 19, 2020
- COVID-19 lung death 4X more likely in Iran if less than 25 ng of vitamin D – Oct 30, 2020
- COVID-19 was killing dark-skinned doctors, then they got a Vitamin D recommendation
- 9X COVID-19 survival in nursing home if had 80,000 IU dose of vitamin D in previous month – Oct 2020
- 14.7 X more likely to die of COVID-19 if less than 12 ng of Vitamin D (185 Germans) – Sept 10, 2020
- COVID ARDS deaths 2X more likely if less than 10 ng of Vitamin D – Aug 8, 2020
- COVID-19 mortality rate highest North of 35 degrees latitude (Vitamin D) – April 20, 2020
- COVID-19 more frequent and deadly for those with dark skins (high risk of low vitamin D)
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Highlights and Abstract
Highlights
•Vitamin D may be a central biological determinant of COVID-19 outcomes.
•Bolus vitamin D3 supplementation during or just before COVID-19 was associated with less severe COVID-19 in frail elderly.
•Bolus vitamin D3 supplementation during or just before COVID-19 was associated with better survival rate in frail elderly.
•Randomized controlled trials are expected to firmly conclude the effect of vitamin D supplementation on COVID-19 prognosis.
Abstract
Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The “Intervention group” was defined as those having received bolus vitamin D3 supplementation during COVID-19 or in the preceding month, and the “Comparator group” corresponded to all other participants. The primary and secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute phase, respectively. Age, gender, number of dmgs daily taken, functional abilities, albuminemia, use of corticosteroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization for COVID-19 were used as potential confounders. The Intervention (n=57; mean士SD,87.7士9.3years; 79%women) and Comparator (n=9; mean? 87.4±7.2 years; 67% women) groups were comparable at baseline, as were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36±17days.
- 82.5% of participants in the Intervention group survived COVID-19, compared to only
- 44.4% in the Comparator group (P=0.023).
The full-adjusted hazard ratio for mortality according to vitamin D3 supplementation was HR=0.11 [95%CI:0.03;0.48],P=0.003. Kaplan-Meier distributions showed that Intervention group had longer survival time than Comparator group (log-rank P=0.002). Finally, vitamin D3 supplementation was inversely associated with OSCI score for COVID-19 (p=- 3.84[95%CI:-6.07;-1.62],P=0.001). In conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly with less severe COVID-19 and better survival rate.
INTRODUCTION
Since December 2019, the COVID-19 caused by SARS-CoV-2 is spreading worldwide from China, affecting millions of people and leaving thousands of dead, mostly in older adults. With the lack of effective therapy, chemoprevention and vaccination [1], focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Importantly, a most recent genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns through their effects on gene expression [2]. In particular, by activating or repressing several genes in the promoter region of which it binds to the vitamin D response element [3], vitamin D may theoretically prevent or improve COVID-19 adverse outcomes by regulating
- (i) the renin-angiotensin system (RAS),
- (ii) the innate and adaptive cellular immunity, and
- (iii) the physical barriers [4].
Consistently, epidemiology shows that hypovitaminosis D is more common from October to March at northern latitudes above 20 degrees [3], which corresponds precisely to the latitudes with the highest lethality rates of COVID-19 during the first months of winter 2020 [1]. In line with this, significant inverse associations were found in 20 European countries between serum 25-hydroxyvitamin D (25(OH)D) concentration and the number of COVID-19 cases, as well as with COVID-19 mortality [5]. This suggests that increasing semm 25(OH)D concentration may improve the prognosis of COVID-19. However, no randomized controlled trial (RCT) has tested the effect of vitamin D supplements on COVID-19 outcomes yet. We had the opportunity to examine the association between the use of vitamin D3 supplements and COVID-19 mortality in a sample of frail elderly nursing-home residents infected with SARS-CoV-2. The main objective of this quasi- experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly COVID-19 patients living in nursing-home. The secondary objective was to determine whether this intervention was effective in limiting the clinical severity of the infection.
MATERIAL AND METHODS
Study population
The study consisted in a quasi-experimental study in a middle-sized nursing-home in Rhone, South-East of France, the residents of which were largely affected by COVID-19 in March- April 2020 (N=96, including n=66 with COVID-19). Data were retrospectively collected from the residents’ records of the nursing-home.
The nursing-home is dedicated to residents with physical disabilities, major neurocognitive and psychiatric disorders. The facility includes 56 single rooms and 21 double rooms, along with communal dining and activity areas. There are no closed units. All residents were allowed to move around the building until 21 March 2020, when social distancing and other preventive measures were implemented. Residents were isolated in their rooms with no communal meals or group activities. No visitors, including families, were allowed in the nursing-home since 10 March 2020. Enhanced hygiene measures were implemented, including cleaning and disinfection of frequently touched surfaces, permanent face masks, and additional hand hygiene stations for staff members.
The inclusion criteria for the present analysis were as follows: 1) residents with cMcally obvious or diagnosed COVID-19 with RT-PCRin March-April 2020; 2) data available on the treatments received, including vitamin D supplementation, since the diagnosis of COVID-19 and during the previous month at least; 3) data available on the vital status and COVID-19 evolution as of May 15, 2020; 4) no objection from the resident and/or relatives to the use of anonymized clinical and biological data for research purposes. Sixty-six residents had COVID-19 during the study period. They all met the other inclusion criteria and were included in the present analysis.
Intervention: bolus vitamin D3 supplementation during or just before COVID-19
All residents in the nursing-home receive chronic vitamin D supplementation with regular maintenance boluses (single oral dose of 80,000 IU vitamin D3 every 2-3 months), without systematically performing serum control test as recommended in French nursing-homes [6] due to the very high prevalence of hypovitaminosis D reaching 90-100% in this population [7]. Here, the "Intervention group" was defined as all COVID-19 residents who received an oral bolus of 80,000 IU vitamin D3 either in the week following the suspicion or diagnosis of COVID-19, or during the previous month. The "Comparator group" corresponded to all other COVID-19 residents who did not receive any recent vitamin D supplementation. None received D2 or intramuscular supplements. All medications were dispended and supervised by a nurse.
Primary outcome: COVID-19 mortality
The primary outcome was mortality of COVID-19 residents during follow-up. Follow-up started from the day of COVID-19 diagnosis for each patient, and continued until May 15, 2020, or until death if applicable.
Secondary outcome: OSCI score for COVID-19 in acute phase
The secondary outcome was the score on the World Health Organization’s Ordinal Scale for Clinical Improvement (OSCI) for COVID-19 [8]. The score was calculated by the geriatrician of the nursing-home during the most severe acute phase of COVID-19 for each patient. The OSCI distinguishes between several levels of COVID-19 clinical severity according to the outcomes and dedicated treatments required,with a score ranging from 0 (benign) to 8 (death). A score of 4 corresponds to the introduction of oxygen (nasal oxygen catheter or oral nasal mask), and a score of 6 to intubation and invasive ventilation [8].
Covariables
Age,gender,number of drugs daily taken, functional abilities, nutritional status, COVID-19 treatment with corticosteroids and/or hydroxychloroquine and/or dedicated antibiotics, and hospitalization for COVID-19 were used as potential confounders. The number of drugs usually taken per day was recovered from prescriptions in the nursing-home and served as a measure of the burden of disease, as previously reported [9]. The use of corticosteroids and/or hydroxychloroquine and/or dedicated antibiotics (i.e., azithromycin or rovamycin) were noted from prescriptions in the nursing-home or during hospitalization, as appropriate. Functional abilities prior to COVID-19 were measured from 1 to 6 (best) with the Iso-Resources Groups (GIR) [10]. Finally, the prognosis related to the nutritional status prior to COVID-19 was evaluated using the last measure of semm albumin concentration during the past semester, as appropriate [11].
Statistical analysis
Participants’ characteristics were summarized using means and standard deviations (SD) or frequencies and percentages, as appropriate. As the number of observations was higher than 40, comparisons were not affected by the shape of the error distribution and no transform was applied [12]. First, comparisons between participants separated into Intervention and Comparator groups were performed using Mann-Whitney U test or the Chi-square test or Fisher test, as appropriate; and then according to mortality. Secondly, a full-adjusted Cox regression was used to examine the associations of mortality (dependent variable) with bolus vitamin D3 supplements and covariables (independent variables). The model produces a survival function that provides the probability of death at a given time for the characteristics supplied for the independent variables. Third, the elapsed time to death was studied by survival curves computed according to Kaplan-Meier method and compared by log-rank test
Finally, univariate and multiple linear regressions were used to examine the association of bolus vitamin D3 supplementation (independent variable) with OSCI score (dependent variable), while adjusting for potential confounders. P-values<0.05 were considered significant. All statistics were performed using SPSS (v23.0, IBM Corporation, Chicago, EL) and SAS® version 9.4 software (Sas Institute Inc).
Standard Protocol Approvals, Registrations, and Patient Consents The study was conducted in accordance with the ethical standards set forth in the Helsinki Declaration (1983). No participant or relatives objected to the use of anonymized clinical and biological data for research purposes. The study was approved by the Ethical Committee of Angers University Hospital (2020/67). The study protocol was also declared to the National Commission for Information Technology and civil Liberties (CNIL).
RESULTS
Sixty-six participants (mean士SD age 87.7士9.0years,range 63-103years; 77.3% women) were infected with SARS-CoV-2 and included in this quasi-experimental study. The mean followup was 36±17 days. Fifty-one people survived COVID-19, while 15 died. The two groups were comparable at baseline with no significant difference regarding the age (P=0.699), gender (P=0.731),the mean number of drugs usually taken per day (P=0.053),the GIR score (P=0.209) and the serum albumin concentration (P=0.263) (Table 1). Regarding care dedicated to CO VID_ 19, only the proportion of patients who received a bolus of vitamin D3 during or just before COVID-19 differed between deceased participants and survivors, with a higher prevalence in survivors (respectively 92.2% versus 66.7%, P=0.023). In contrast, there was no between-group difference in the proportion of patients treated with corticosteroids, hydroxychloroquine or dedicated antibiotics, or hospitalized for COVID-19.
Table 1 indicates the characteristics of participants separated into Intervention (n=57) and Comparator (n=9) groups. Their baseline characteristics (age, gender, albuminemia) did not differ between groups, with the exception of the number of drugs usually taken (which involved the use of vitamin D supplements) and the disability score (Table 1). Similarly, the proportion of participants at each OSCI severity level as well as the use of dedicated COVID- 19 dmgs did not differ between Intervention and Comparator groups. At the end of the follow-up, 82.5% of patients from the Intervention group survived COVID-19, compared to only 44.4% in the Comparator group (P=0.023).
Figure 1 shows a statistically significant and clinically relevant protective effect against mortality of bolus vitamin D3 supplementation received during or just before COVID-19. The hazard ratio (HR) for mortality according to vitamin D3 supplementation was 0.21 [95% confidence interval (95%CI): 0.07;0.63] P=0.005 in the unadjusted model, and HR=0.11 [95%CI: 0.03;0.48] P=0.003 after adjustment for all potential confounders. No other covariables were associated with mortality, in particular no other dedicated treatments. Using the season of the COVID-19 diagnosis as an additional potential confounder did not affect the results (data not shown). Consistently, Kaplan-Meier distributions showed in Figure 2 that the residents who had not recently received vitamin D3 supplements had shorter survival time than those having received vitamin D3 supplementation during or just before COVID-19 (log- rank P=0.002).
Finally, the linear regression model illustrated in Table 2 showed that bolus vitamin D3 supplementation during or just before COVID-19 was inversely associated with the OSCI score for COVID-19 in acute phase. Similar results were found before (P=-2.96 [95%CI:- 4.79;-1.12], P=0.002) and after adjusting the analyses for potential confounders (p=-3.84 [95%CI: -6.07;_1.62],P=0.001).
Portion of table 2
DISCUSSION
The main finding of this nursing-home-based quasi-experimental study is that, irrespective of all measured potential confounders,bolus vitamin D3 supplementation during or just before COVID-19 was associated with less severe COVID-19 and better survival rate in frail elderly. No other treatment showed protective effect. This novel finding provides a scientific basis for vitamin D replacement trials attempting to improve COVID-19 prognosis.
To our knowledge we provide here the first quasi-experimental data examining the effect of vitamin D supplementation on the survival rate of COVID-19 patients. To date, only rare observational data, all of which are consistent, are available on the link between vitamin D and COVID-19. The first reports in COVID-19 patients indicated that hypovitaminosis D is highly prevalent in this population, reaching 85% [13], and that semm 25(OH)D concentrations are lower in COVID-19 patients compared to controls [14]. Similarly, significant inverse correlations were found in 20 European countries between the mean semm 25(OH)D concentrations and the number of COVID-19 cases/lM, as well as with mortality/1M [5]. The severity of hypovitaminosis D appears to relate to the prognosis of COVID-19 since the mortality rate was multiplied by 7.6 among people with hypovitaminosis D <75nmol/L, and by 10.1 among those with hypovitaminosis D <50nmol/L (P<0.001) [15]. Similarly, another observational study in 212 COVID-19 cases showed that, for each standard deviation increase in semm 25(OH)D, the probability of mild rather than severe COVID-19 was multiplied by 7.9 (P<0.001), while the probability of mild rather than critical COVID-19 was multiplied by 19.6 (P<0.001) [16]. These results suggest that increasing semm 25(OH)D concentration may improve the prognosis of COVID-19. Interventional studies dedicated to COVID-19 are yet warranted for investigating the role of vitamin D supplementation on COVID-19 outcomes. Interestingly, previous meta-analyses found that high-dose prophylactic vitamin D supplementation was able to reduce the risk of respiratory tract infections [17]. Based on this observation, we and others are conducting anRCT designed to test the effect of high-dose versus standard-dose vitamin D3 on 14-day mortality in COVID-19 older patients (https://clinicaltrials.gov/ct2/show/NCT04344041). While waiting for the recmitment of this RCT to be completed, the findings of the present quasi-experimental study strongly suggest a benefit of bolus vitamin D3 supplementation on COVID-19 outcomes and survival.
How vitamin D supplementation may improve COVID-19 outcomes and survival is not fully elucidated. Three mechanisms are possible: regulation of (i) the RAS, (ii) the innate and adaptive cellular immunity, and (iii) the physical barriers [4]. First, vitamin D reduces pulmonary permeability in animal models of acute respiratory distress syndrome (ARDS) by modulating the activity of RAS and the expression of the angiotensin-2 converting enzyme (ACE2) [18]. This action is cmcial since SARS-CoV-2 reportedly uses ACE2 as a receptor to infect host cells [19] and downregulates ACE2 expression [20]. ACE2 is expressed in many organs, including the endothelium and the pulmonary alveolar epithelial cells, where it has protective effects against inflammation [21]. During COVID-19, downregulation of ACE2 results in an inflammatory chain reaction, the cytokine storm, complicated by ARDS [22]. In contrast, a study in rats with chemically-induced ARDS showed that the administration of vitamin D increased the levels of ACE2 mRNA and proteins [23]. Rats supplemented with vitamin D had milder ARDS symptoms and moderate lung damage compared to controls. Second, many studies have described the antiviral effects of vitamin D, which works either by induction of antimicrobial peptides with direct antiviral activity against enveloped and non- enveloped viruses, or by immunomodulatory and anti-inflammatory effects [24]. These are potentially important during COVID-19 to limit the cytokine storm. Vitamin Dean prevent ARDS [25] by reducing the production of pro-inflammatory Thl cytokines, such as TNFa and interferon y [24]. It also increases the expression of anti-inflammatory cytokines by macrophages [24]. Third, vitamin D stabilizes physical barriers [4]. These barriers are made up of closely linked cells to prevent outside agents (such as viruses) from reaching tissues susceptible to viral infection. Although viruses alter the integrity of the cell junction, vitamin D contributes to the maintenance of functional tight junctions viaE-cadherin [4]. All these antiviral effects could potentiate each other and explain our results.
We also found that none of the other dedicated dmgs used in this quasi-experimental study was associated with better survival rate in COVID-19 patients. The interest of these drugs in COVID-19is still debated, whether for corticosteroids [26], hydroxychloroquine [27] or azithromycin [28]. However, it should be noted that these drugs were given here as part of patient care in the most severe clinical situations, which could have biased and masked their effectiveness (if any).
The strengths of the present study include i) the originality of the research question on an emerging infection for which there is no scientifically validated treatment, ii) the detailed description of the participants’ characteristics allowing the use of multivariate models to measure adjusted associations, and iii) the standardized collection of data from a single research center.
Regardless, a number of limitations also existed. First, the study cohort was restricted to a limited number of nursing-home residents who might be unrepresentative of all older adults. Second, although we were able to control for the important characteristics that could modify the association, residual potential confounders might still be present such as the semm concentration of 25(OH)D at baseline - alow level classically ensuring the effectiveness of the supplementation [29]. As this analysis was not initially planned, no concerted efforts were made to systematically measure the semm 25(OH)D concentration before and after supplementation. Third, the quasi-experimental design of our study is less robust than an RCT. Participants in the Comparator group did not receive vitamin D placebo, and there was no randomization. It should yet be noted that the characteristics of the two groups did not differ at baseline, which allows interpreting the survival difference as linked to the vitamin D3 supplementation.
CONCLUSIONS
In conclusion, we were able to report among frail elderly residents that bolus vitamin D3 supplementation taken during or just before COVID-19 was associated with less severe COVID-19 and better survival rate. No other treatment showed protective effect.
Vitamin D3 supplementation may represent an effective, accessible and well-tolerated treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no validated treatments. Further prospective, preferentially interventional, studies are needed to confirm whether supplementing older adults with bolus vitamin D3 during or just before the infection could improve, or prevent, COVID-19.
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- Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ 2020;369:ml432. doi: 10.1136/bmj.ml432.
- Gbinigie K, Frie K. Should azithromycin be used to treat COVID-19? A rapid review. BJGP Open 2020 Epub May 12. pii: bjgpopen20X101094. Doi: 10.3399/bjgpopen20Xl 01094
- Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev 2014;72:48-54.
See also in VitaminDWiki
COVID-19 news
COVID-19 and Dark Skins
COVID-19 treated by Vitamin D - studies, reports, videos
As of Aug 22, 2023, the VitaminDWiki COVID page had: 19 trial results, 37 meta-analyses and reviews, Mortality studies see related: Governments, HealthProblems, Hospitals, Dark Skins, All 26 COVID risk factors are associated with low Vit D, Fight COVID-19 with 50K Vit D weekly Vaccines Take lots of Vitamin D at first signs of COVID 166 COVID Clinical Trials using Vitamin D (Aug 2023) Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
5 most-recently changed Virus entries
Recent Vitamin D and COVID-19 Click here for all VIRUS articles on VitaminDWiki
- Athletes who had been COVID infected had lower Vitamin D levels – July 2023
- Vitamin D was the most popular supplement during the COVID Pandemic – July 2023
- COVID cost the US 18,000 dollars per survivor, and many excess deaths - July 2023
- COVID, Long-COVID and Vitamin D in children - Review April 2023
- COVID in hospital stopped by Vitamin D Receptor activators (curcumin, quercetin) – RCT June 2023
- Children with COVID 4X more likely to have poor Vitamin D Receptors (Note: COVID deactivates VDR) – April 2023
- Chance of moderately severe COVID 3X less likely if plant-based diet – April 2021
- COVID, Long COVID, and Vitamin D – May 2023
- 3,400 peer-reviewed studies found COVID Vaccination problems as of April 2023
- COVID death 1.5 X less likely if high vitamin D, emergency D (50K to 100K) is great – meta-analysis March 2023
- Poor vaccine batches associated with adverse events - March 2023
- Probably less of a problem if had high Vitamin D when vaccinated
- Excess deaths - 5 possible reasons - many studies
- COVID was associated with low Vitamin D or Zinc – umbrella review Feb 2023
- COVID predicted to be a pandemic that could be stopped by high dose vitamin D - Feb 2020
- COVID and other Virus fought by UV - many studies
- Seniors raised Vitamin D levels, more COVID survivors, less CKD (Slovakia) – Feb 2023
- COVID recovery 1.6X faster after 200,000 IU of Vitamin D RCT – Feb 2023
- Multisystem Inflammatory Syndrome of COVID in Children 3X more likely if low Vitamin D – Feb 2023
- COVID was associated with low Vitamin D or Zinc – umbrella review Feb 2023
- Vitamin D, now conclusive (for COVID) - Dr. Campbell Video and transcript - Feb 1, 2023
- COVID ICU 3X less-likely if take any amount and type of Vitamin D – meta-analysis Jan 2023
- 2nd COVID infection increases the risk of Long-COVID - 2022
- More COVID vaccinations, more infections - Cleveland Clinic - Dec 2022
- COVID vaccination increased by 137X the risk of 10-14 year olds of dying (UK) – Jan 2023
- Chart of excess deaths and vaccination in the Netherlands - for 2022
- China: From Zero Covid to No Plan - people left to improvise - NYT Dec 18, 2022
- COVID variants in US evade bivalent vaccination by 3X to 13X – Cell Dec 13, 2022
- Fight infections such as COVID with 50 ng of Vitamin D – Sunil Dec 2022
- COVID and Vitamin D: any amount of D, at any time, for any duration reduced ICU - meta-analysis Dec 2022
- The vitamins and minerals that help the immune system respond to respiratory viruses – Dec 2022
- The COVID supplement with the most publications: Vitamin D – Nov 2022
- 23 COVID mitigation strategies: at least 6 of which increase Vitamin D in cells - Sept 2022
- Severe COVID 1.8 X more likely in pregnant women with less than 15 ng of vitamin D – Nov 2022
- Long-COVID fatigue reduced by Vitamin C and l-Arginine in one month– RCT Nov 2022
- COVID 2X more likely to be severe if low Vitamin D in previous month (Denmark, May 2020) – Nov 2022
- Respiratory viral infection (RSV) and low vitamin D - many studies
- T1 Diabetic adults 5X more likely to get COVID (hint low vitamin D)– Nov 2022
- Prevent a COVID death: 9 dollars of Vitamin D or 900,000 dollars of vaccine - Aug 2023
- COVID US deaths: 116,000 fewer if everyone had been taking 50,000 IU Vitamin D – Campbell transcript Nov 2022
- COVID existed in the second half of 2019 - several studies nothing about Vitamin D
- PICU layoffs due to pandemic lulls, but children are now getting 3 years of viral infection all at once – Oct 2022 nothing about Vitamin D
- Fatigue and other long-haul problems appear to be associated with low Magnesium - Chambers Oct 2022
- Long-COVID symptoms in 10 Percent of women 3 months after infection (22 countries) – Oct 2022 nothing about Vitamin D
- COVID-Osteoporosis association appears to be low Vitamin D – Oct 2022
- Low Magnesium associated with severe COVID – many studies
- 10,000 COVID infections: Hospitalization 2.4X more likely if low vitamin D - Oct 2022
- BIDEN: "Almost everyone who will die from COVID this year will not be up to date on their shots." (nope) - Oct 2022
- Tripledemic: Flu, COVID, and RSV (all fought by Vitamin D) - Oct 2022
- COVID: more than 33 lineages and vaccines – Nov 2022 nothing about Vitamin D
- 1,000 X lower COVID mortality rate in 2020 for age 10 vs 65 – Oct 2022
- COVID 5.5 X more likely to be severe if low Vitamin D (children in this case) – Oct 2022
- Vitamin D was the most popular nutraceutical to avoid COVID – 41 percent of dentists in Brazil – Oct 2022
- The more COVID vaccinations you get, the More Likely you’ll get COVID - Oct 2022
- CDC v-safe vaccination data is finally on-line - Oct 5, 2022
- 400 doctors, scientists declare “international medical crisis” due to COVID-19 vaccinations - Sept 2022
- Hair loss is increased by stress: example 4X increase by COVID (hint: Vitamin D) – Sept 2022
- COVID in hospital fought by Vitamin D (25,000 IU daily for 4 days, then 25K weekly) - RCT – July 2022
- We had an inexpensive life-saving solution both before and during the pandemic (Vitamin D) - Malone May 2022
- Australia’s COVID Response resulted in 31 X more life years lost than were saved - Sept 2022
- Congress members demand FDA Investigate COVID-19 Vaccine Injuries – Sept 2022
- Early puberty during pandemic (perhaps just low vitamin D) - Sept 2022
- Vitamin D energizes the innate and adaptive immune systems to fight lung inflammation – Sept 2022
- COVID increased seniors risk of Alzheimer's by 1.7X in the next year- Sept 2022
- Pfizer vaccination trial – 1 in 800 actually had a serious adverse event – Sept 2022
- Model discovered: More UV, less COVID (many excellent charts) – Sept 2022
- COVID kids were more likely to have a poor VDR (4.3 X), than low Vitamin D (2.6 X) – Sept 2022
- Worse COVID during 3Q pregnancy if 2.5 ng lower Vitamin D – meta-analysis Sept 2022
- COVID fought by the antioxidants: Vitamin D, Zinc, Vitamin C, and Selenium – Review Sept 2022
- Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts - Aug 2022
- Many viral infections can be fought by Vitamin D (Astronaut’s in this case)– Aug 2022
- COVID worse if lower Vitamin C, but not Vitamin D in this study – Aug 2022 Why C but NOT D?
- Vitamin D improves Sinovac vaccine (fast innate response) - July 2022
- COVID survival in Europe in 2020 best predicted by population-level Vitamin D (of 13 variables) – July 2022
- Vitamin D can provide HEALTH immunity to fight the Corona virus this fall - Aug 2022
- Super-immune do not get COVID symptoms (perhaps Vitamin D) - Aug 2022
- COVID children helped by Vitamin D, trial terminated: unethical to not give Vitamin D to all: – RCT July 2022
- Current Compherensive Approach to COVID-19 (293 pages) - July 2022
- Some countries give treatment kits containing vitamin D if test positive for COVID - July 2022
- Elderly who had been in COVID ICU were 4X more likely to die if low vitamin D – Nov 2022
- Pandemic of the Boosted: UK Data Reveal Problem With COVID Vaccinations - July 2022
- Pandemic Vitamin D levels dropped by 3.3 ng (perhaps less D, more health problems) – May 2022
- Long-COVID is now the biggest COVID concern - many studies
- Severe COVID 2.6 X less likely if supplement with Vitamin D – 26th meta-analysis - July 2022
- Calcifediol is in the title of 7 virus pages as of June 2022
- Some COVID hospitalizations are due to poor Vitamin D genes (Binding Protein in this commentary) – June 2022
- COVID, Cancer, etc. are Vitamin D low-hanging-fruit – Editorial June 2022
- COVID deaths are often of fully vaccinated in fully vaccinated countries – June 2022
- Both Omicron and Monkeypox show evidence of mutation by the human immune system – June 2022
- Treat COVID early with high-dose Vitamin D (20th as of June 2022)
- Vitamin D might mitigate endemic COVID - June 2022
- Vitamin D also provides COVID Neuroprotection – April 2022
- 89% are vaccinated, but Omicron BA.5 is surging (Portugal) June 2022
- COVID hospital deaths reduced 2X by 8 days of UVB – pilot RCT May 2022
- Surviving COVID with vitamins and minerals is not a myth – June 2022
- Vitamin D is the only one which: 1) Can be done at home, 2) Needs only a single dose
- 400,000 IU of vitamin D 3 days after COVID symptoms reduced 14 day mortality by 3X – Annweiler RCT May 2022
- COVID patients not helped by 500K IU of Vitamin D (they already had enough) – May 2022
- Suspect that they did not get the Vitamin D until 1 week after getting symptoms
- both groups had adequate vitamin D levels upon entering hospital
- COVID-19 Is Treatable and Preventable With Vitamin D: Dr. Malone - May 24, 2022
- Less COVID if more vitamin D from food (Spain) – May 2022
- You Are Going to Get COVID Again … and Again … and Again once every 3 years
- Unless you take Vitamin D
- Omicron BA.2.12.1 - US dominate form,100,000 cases daily - May 24, 2022
- Problems after childhood vaccinations - many studies - perhaps fewer problems if more Vitamin D
- Loading dose of Vitamin D for patients hospitalized with COVID (140,000 IU) – RCT completed 2021
- COVID Ventilation 2X less likely if 200,000 IU of Vitamin D when enter hospital – May 2022
- COVID in seniors 5X less likely to be severe if vegetarian (small study) – April 2022
- Inhaling Nitric Oxide 4 times a day (which increases Vitamin D) fights COVID - May 2022
- Forecast of 100 million more US COVID infections in fall and winter - May 2022
- Vitamin D, Immune function, and SARS-CoV2 – May 2022
- COVID death 5.2X more likely if Vitamin D deficient – May 2022
- Severe COVID while pregnant - none had taken any vitamin D – Oct 2021
- Risk factors for severe COVID in children are all related to low vitamin D (same as adults) - April 2022
- Innate immune suppression by SARS-CoV-2 mRNA vaccinations - April 2022
- Dr. McCullough is one of the authors, in-depth look at VARS 2021 data
- COVID death 6.9X less likely if high Magnesium to Calcium ratio – April 2022
- 13 Magnesium and COVID studies in VitaminDWiki
- 21 fewer days in hospital with ARDS (COVID) if 10,000 IU of Vitamin D daily after enter hospital – RCT April, 2022
- Speculation: "No hospitalization if had gotten high dose vitamin D at COVID symptom onset"
- 4X less likely to get COVID following 4,000 IU daily for a month – RCT April 2022
- COVID and CVD deadly pandemics share a risk factor: low vitamin D - April 2022
- 29 X more likely to die of COVID if less than 20 ng of Vitamin D - March 2022
- 2.9 X less risk of COVID ICU if seniors had supplemented with Vitamin D (any amount) – April 2022
- Data from Spring of 2020. Wonder why the 2 year delay
- Micronutrients such as vitamin D should improve vaccine effectiveness (and decrease side effects) – April 2022
- High altitudes reduce the COVID-19 infection (not a surprise) – April 2022
- Obesity, Hypovitaminosis D, and COVID-19 – April 2022
- COVID while pregnant: 2.6 X more likely to be Vitamin D deficient (need to supplement) - March 2022
- Pfizer vaccine produced 30 percent more antibodies if more vitamin D – July 2022
- COVID-XE variant can probably be fought by strong immune systems (Vitamin D, etc.) - April 2022
- COVID Long-Haul at 49 weeks: overactive immune system, type O blood - March 2022
- CDC and UK data reveal the COVID vaccines do not prevent cases, transmission, severe illness or deaths - April 3, 2022
- Children have less severe COVID, but just as much long-haul as adults - April 2022
- COVID-XE variant can probably be fought by strong immune systems (Vitamin D, etc.) - April 2022
- COVID breakthru 2X more likely if pregnant (should take Vitamin D) - April 2022
- COVID, like influenza, may be able to mutate to avoid vaccines for decades - March 2022
- Increase in COVID Omicron deaths among vaccinated (CA this time) - March 2022
- Risk of COVID not reduced by 3,200 IU of vitamin D during 6 months (no surprise) – RCT March 2022
- COVID length of stay: the best predictor was Vitamin D (of 70 parameters) – March 2022
- Review of Early Treatments of COVID-19 (within a few days of symptoms)
- Omicron-1 survives on surfaces 3X longer than original - March 18, 2022
- Compare symptoms of Omicron, Flu and Colds Vitamin D fights all of them
- Immune system both activates and uses vitamin D (in brain, fight COVID, etc.) - March 2022
- COVID length of stay: The best predictor was Vitamin D (of 70 parameters) – March 2022
- COVID: most places are dropping restrictions, some are surging, and a few are both - March 15, 2022
- Giving Vitamin D often reduced COVID Mortality– Review of 11 studies – March 2022
- 18 million excess global deaths in past 2 years: COVID plus collateral damage - Lancet March 2022
- decreased Vitamin D due to lock-up is one of the possible causes
- Vitamin D of 30-40 ng fights COVID, Dr. Grimes on Liverpool Study - March 2022
- Vitamin D separately helps X or COVID, should help X with COVID (example: diabetes) – March 2022
- Recall: 26 health problems associated with increased COVID risk, ALL are assoicated with low vitamin D
- COVID can be fought by healthy immune systems (vitamins, etc.) - Feb 2022
- Note elsewhere: Vitamin D improved immune system so much that half did not even test positive 24th meta-analysis
- Vitamin D helps both the innate and adaptive immune systems fight COVID-19 – Jan 2022
- Only a single supplement taken before infection decreased COVID severity (vitamin D) – Feb 2022
- COVID children with multisystem inflammatory syndrome have less than 10 ng of vitamin D – March 2022
- Vitamin D supplementation reduced risk of COVID-19 ICU by 2.8 X – review of 10 reviews Feb 2022
- COVID vaccination makes 6X more antibodies in those having good levels of both vitamin D and Iron – June 2021
- VitaminDWiki interview and transcript - Jan 2022 143 minute - includes a section on early treatments for COVID
- 14 X less likely to have severe COVID if previously had more than 40 ng level of Vitamin D – Feb 2022
- How vitamins A, B, C, D, E, F (Omega), K fight COVID - Feb 2022
- Estrogen supplements may cut COVID-19 deaths by half (no surprise - more E, more Vitamin D) - Feb 2022
- Group achieving 30 ng (vs 26 ng) were 2X less likely to get COVID symptoms - RCT Jan 2022
- Vitamin D helps both the innate and adaptive immune systems fight COVID-19 – Jan 2022
- COVID test positive is about half as likely if have Vitamin D – 24th meta-analysis - Jan 2022
- FLCCC COVID guidelines now include vitamin D loading doses - Jan 2022
- Vitamin D and its’ role in Parkinson’s disease patients with COVID - Jan 2022
- COVID death rate was 3X lower in those with Multiple Sclerosis (85 pcnt were taking Vitamin D) - Jan 2022
- Vitamin D fights COVID (54 studies of 1,400,000 people) – 23rd meta-analysis - Dec 2021
- Vitamin D benefits ignored at a time they are most needed - Grant Jan 9, 2022
- Increase in non-COVID deaths (ages 18-64) in Indiana, India, etc. - Jan 5, 2022
- Vitamin D and COVID-19: a narrative review - Holick - Jan 4, 2022
- Two times less likely to test positive for COVID if vitamin D level more than 55ng, etc. – Dec 31, 2021
- Vitamin D and COVID - Davies, Benskin (Dark Horse video with transcript) - Dec 27, 2021
- Ivermectin taken before COVID decreased death rate by 68 percent (3,000 with Ivermectin vs 3,000 without) - Dec 24, 2021
- The Vitamin D Receptor is associated with many health problems perhaps SARS-COV-2 as well
- Dr. McCullough on COVID-19: vaccine problems, home treatment – video, transcript – Dec 13, 2021
- Far fewer vaccination antibodies against Omicron - Dec 14, 2021
- Did HIV help Omicron evolve - Dec 10, 2021
- COVID-19 death increased 2X if low Vitamin D (less than 10 to less than 30 ng) – 21st meta-analysis Dec 2021
- Most COVID patients had sticky blood platelets (Omega-3 helps) - Dec 2021
- 16,000 Physicians and Scientists Agree Kids Shouldn’t Get COVID Vaccine - Dec 15, 2021
- Florida A.G. recommends Vitamin D, Zinc, Quercetin, etc. to reduce risk of COVID - Dec 12, 2021
- Vitamin D and a Dr. in Israel - Campbell video and transcript - Dec 11, 2021
- Epstein-Barr Virus probably causes Long-COVID, CFS, and MS - many studies
- Pfizer knew of 290 kinds of COVID vaccine problems
- Vaccinated have HIGHER infection rates than unvaxxed (UK age 30-70) - Dec 9, 2021
- Rapid Vitamin D Delivery May Result in Better COVID Outcomes - Dec 9, 2021
- 11,321 Breakthru COVID cases in Massachusetts last week (fully vaccinated) - Dec 7, 2021
- COVID vaccines produce blood antibodies, not the needed mucosal antibodies - Dec 7, 2021
- also has several Vitamin D & COVID videos
- Coronaviruses evolve faster with vaccinations, expect more beyond Omicron - Nov 30, 2021
- Omega-3 decreases heart disease and COVID: Harris and Patrick, video and transcript - Dec 2021
- COVID is also associated with low Vitamin K - many studies
- Compulsory COVID Interventions do not work (400 studies - GreenMed Info) Dec 1, 2021
- Vitamin D loading doses quickly and safely raise levels – meta-analysis Dec 2021
- Real Anthony Fauci - book synopsis by Masterjohn Dec 3, 2021
- Large dose of calcifediol or vitamin D up to 15 days before COVID hospitalization reduced death rates (1.5X, 1.3X) – Dec 2021
- COVID-19 infection risk 2X higher in vaccinated than previously infected (28,000 in Netherlands) – preprint Nov 24, 2021
- Higher COVID death rates in more obese counties - Dec 2021
- COVID Virus kept mutating for 154 days in an immunocompromised person – Dec 2020
- COVID-19 risk reduction by Vitamin D, etc. - Grassroots Health Nov 29, 2021
- Vitamin D appears to drop while fighting COVID but recover later – Nov 2021
- How obesity reduces the ability of vitamin D to fight health problems such as COVID - Nov 2021
- Vaccinated were 28 percent of cases, 23 percent of deaths (waning)- CDC Sept 2021
- 11 percent fewer COVID-19 deaths if lockdowns had allowed sunshine – Nov 2021
- Long-Haul COVID is somewhat less of a problem if vaccinated – Nov 2021
- Elderly vaccinated for COVID were 2X more likely to die of ischemic stroke (2930 vs 1180 deaths)– Nov 2021
- Younger are much less likely to die of COVID than elderly (posters) - Nov 2021
- 3.3 X more likely to die if infected with SARS-Cov-2 plus a second pathogen – meta-analysis May 2021
- Pfizer trial vaccinated 22,000: 1 COVID death prevented, but 4 died of heart attacks - Nov 2021
- Problems with vaccine use during a pandemic - Dr. Bossche 2021 - 2023
- 3,900 deaths within 2 weeks of 2nd vaccination in Sweden - Nov 18, 2021
- Discussion of COVID and 50 ng of Vitamin D (video and transcript)– Dr. Campbell Nov 17, 2021
- Vaccine definition by the CDC seems to now include Vitamin D - Sept 2021
- US is buying 5 billion dollars of Pfizer COVID pills (10 million dollars of Vitamin D might do as well) - Nov 2021
- Vaccination immunity is waning - Fauci - Nov 14, 2021
- Low Vitamin D etc. more than 3 months after COVID hospitalization – Sept 2021
- Bill Gates admits COVID-19 vaccines don't stop viral transmission - Nov 5, 2021
- COVID, influenza, hepatitis B, measles, etc. vaccine responses vary with Vitamin D and its receptor
- 2X more male teens died than normal in England this summer (perhaps vaccination) - Oct 2021
- Vaccine passports expire in 6 months in Israel, but not (yet) in the US - Oct 2021
- COVID probably fought by Vitamin D, might need 50 ng - Dr. Patrick Nov 8, 2021
- COVID-19 risk reduced by vitamin D supplementation – umbrella review of 7 meta-analysis – Oct 2021
- Perhaps 3X more likely to catch COVID-19 in a group (church) in Nov 2021 than Nov 2020
- Vaccination effectiveness dropped from 83 percent to ZERO after 9 months (Sweden, preprint) – Oct 2021
- COVID natural Immunity is most likely better than vaccination immunity- literature review by Masterjohn - Oct 2021
- COVID winter is coming again in Northern US, Canada, Europe, Russia - Nov 2021
- French recommended 200,000 IU of Vitamin D to stop COVID-19 - Jan 2021
- COVID-19 severity associated with 3 vitamin D genes – Oct 2021
- Vitamin D was the only supplement that fought COVID-19 (out of 6) – Oct 2021
- Colin Powell died of COVID-19 (he had 4 risk factors for low vitamin D) – Oct 18, 2021
- https://vdmeta.com/
- COVID-19 treated by Vitamin D (example: ICU reduced by 5X) – 20th meta-analysis Oct 13, 2021
- COVID-19 and Vitamin D (42 studies, consensus) – Oct 2021
- Vitamin D was a top COVID-19 treatment at 4 hospital groups - May 2021
~ 83,000 patients
- COVID-19 and Vitamin D - Wikipedia Oct 10, 2021
- COVID-19 risk reduction by early treatment: 5X Vitamin D – Oct 8, 2021
- Dr. McCullough on COVID-19: vaccine problems, home treatment – video, slides, transcript – Oct and Dec 2021
- COVID-19 symptoms and comorbidities associated with the type of Vitamin D Receptor – Oct 2021
- COVID-19 and Vitamin D – expert consensus and guidelines (Annweiler, behind paywall) – Oct 2021
- Pfizer vaccine half as effective as Moderna after 6 months (fading or Delta) - Mayo preprint Aug 2021
- Severe COVID-19 2.5 X more likely if low vitamin D (23 studies) – 19th meta-analysis Oct 2021
- COVID-19 cases vs. vaccination (counties and countries) - Sept 2021
- 7 Symptoms predictive of COVID-19 (from 1,000,000 in UK) – Oct 2021
- Emergency treatments if get COVID-19 symptoms - Oct 2021
Dr. Annweiler, an author of this study, has RCT #6