9X COVID-19 survival in nursing home if had 80,000 IU dose of vitamin D in previous month – Oct 2020

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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

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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.

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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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• 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 may cause Long-Haul, CFS, and MS (Vitamin D should help)
• 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, 2022
• 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
• 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
• COVID-19 patients had low levels of Zinc, Vitamin A, Vitamin D, and Vitamin C – Sept 2021
• US COVID-19 deaths now exceed 1918 flu, soon AIDS (Vitamin D fights all 3) - Sept 19, 2021
• Predict 2X more likely to die of COVID-19 if vitamin D Deficient (Iran 2020) – Sept 2021
• COVID-19 appears reduced by Resveratrol plus 100K IU of vitamin D – Small RCT Sept 2021
• COVID-19 Vitamin D Clinical Trials - US Sept 15, 2021 36 trials
• Long-haul, VAERS, Ivermectin, vaccines, etc. Drs. Seheult, Patrick: Video with table of contents - Sept 17, 2021
• Vitamin D might augment COVID-19 vaccines – 6 papers as of Dec 2021
• COVID-19 risk reduced 4X by each of: Vitamin D, Omega-3, Curcumin, Zinc (each increases D in cells)
• COVID-19 risk reduction by early treatment: 5X Vitamin D – Oct 8, 2021
• Vitamin D and Health video with transcript - Dr. Grant Sept 2021
• Influence of Vitamin D on COVID-19 (Guidebook) - Benskin Sept 2021
• Vitamin D and COVID, review of evidence, loading dose if less than 50 ng - Masterjohn Sept 2021
• Higher vitamin D, less severe COVID and deaths in hospital (in Iran this time) – Sept 2021
• COVID-19 therapeutics and cytokine storms (vitamin D occurs 51 times) – Aug 2021
• Many Vitamin D metabolites: some help skin aging, reduce Cytokine storms, but are not tested – Aug 2021
• Fauci investing 3 billion dollars to develop a safe pill to fight virus (but we already have 3) – Aug 4, 2021
• US coalition of Black and Latino churches hope to reduce the 3X COVID-19 disparity - Aug 2021
• Less than 10 dollars of Vitamin D per COVID-19 life saved in Myanmar - Jan 2021
• Effectiveness of COVID-19 vaccines might be increased by Vitamin D – Aug 2021
• Various forms of Vitamin D should be able to fight COVID-19 (model) – Aug 2021
• Vaccinated and Unvaccinated are just as infectious after catching COVID-Delta (UK study) - Aug 2021
• In-home testing of viral load, etc. Dr. Topol interview with transcript – Aug 11, 2021
• Boosting Immunity with Vitamin D to reduce COVID-19 risks - Aug 2021
• A virus can mutate to avoid a vaccine, need more than vaccines to fight a virus – July 31, 2021
• COVID-19 mortality was associated with vitamin D deficiency of 47 countries – July 2021
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• Severe COVID-19 5X more likely if low vitamin D (23 studies) – 16th meta-analysis July 2021
• Initial efficacy of vaccines against COVID-Delta - July 20, 2021
• Taking vitamin D (guess 600 IU avg) reduced US COVID-19 risk by 25 percent (more D would be better) – July 2021
• Many drugs, such as Vitamin D, decrease the risk of COVID-19 – July 2021
• Vaccine effectiveness may drop to only 16% in 6 months if time between jabs was only 3 weeks – July 2021
• Vitamin D known to fight 8 classes of health problems, probably fight COVID-19 as well – July 2021
• Vitamin D, C, A, and E, as well as Iron, Se, and Zinc each augment vaccine response – July 2021
• Vitamin D is one of 14 ways proven to treat COVID-19 – July 2021
• COVID-19 death 40 percent less likely if supplemented with Vitamin D and got above 30 ng (Spain 108,000 people) – July 2021
• Severe pediatric COVID 5.5 more likely if low vitamin D (review of 6 studies) -July 2021
• 5,000 U daily raised Vitamin D a bit and helped COVID-19 a bit – RCT June 2021
• Severe COVID-19 3.5 more likely if low vitamin D (30 studies) – meta-analysis July 2021
• 7X less likely to go to ICU if COVID-19 ward gave calcifediol (semi-activated Vitamin D) – July 2021
• Poor food, little intense exercise again associated with low Vitamin D (and more COVID-19 in this case) – July 2021
• If low vitamin D, 2.5X more likely enter hospital with COVID-19 (UK, 10 months) – June 17, 2021
• COVID-19 patients who had supplemented with Vitamin D were 3X less likely to enter ICU – June 2021
• Vitamin D and COVID-19 both affect immune cells – June 2021
• Pandemics are now every few years, next might be in 2025 (Vitamin D levels have crashed) – June 2021
• Higher rate of serious Vaccination problems than COVID-19 deaths – June 24, 2021
• COVID-19 5X worse if poor Vitamin D gene (CYP2R1) – June 2021
• 600,000 IU of Vitamin D helped 26 out of 28 COVID-19 patients in ICU (Brazil and Bolivia) June 2021
• 3 billion dollars being spent on developing a pill to treat pandemic viruses (ignoring Vitamin D)
• COVID-19 death in hospital 5X more likely if low vs high vitamin D – preprint June 2021
• COVID-19 and variants are here to stay (he fails to mention that vitamin D might help) - June 2021
• Vitamin D reduces COVID-19 complications – June 2021
• How Vitamin D, Magnesium, Omega-3 and Zinc prevent and treat COVID-19 and many other health problems – June 2021
• More than enough evidence on the Yellow Card system to declare the COVID-19 vaccines unsafe for use in humans. - June 9, 2021
• COVID-19 deaths 1.7X more likely if low vitamin D (even after “adjusting” for low D health problems) – May 2021
• Vitamin D has the most supporting science of all micronutrients to fight COVID-19 – May 2021
• COVID-19 fought by Vitamin D, how much more evidence is needed -May 2021
• COVID-21 (COVID-19 with mutations) causing increased pregnancy problems in Brazil and India – May 2021  Pregnancy
• COVID-19, dark skin, pregnancy - Dr. Grimes, etc. - May 2021   Pregnancy
• Increased pregnancy problems with COVID-19 – meta-analysis and letter to editor – April 2021   Pregnancy
• Vitamin D Receptor activation should reduce ARDS associated with COVID-19 - June 2020
• Half of COVID-19 death rate differences explained by rates of elderly influenza vaccination and low vitamin D – April 2021
• COVID-19 inflammation extinguished by 60,000 IU of vitamin D nanoemulsion daily for a week – RCT May 2021
• Treatments for 303,000 COVID-19 patients: vitamin D is both popular and over-the-counter – May 2021 Red = Vitamin D
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• Dr. Fauci speculates on future use of masks in the winter (when vitamin D levels are low) May 2021
• Country reliant on tourism vaccinated, but now 1 in 1,000 get COVID-19 daily - May 2021
• Many supplements appear to fight COVID-19 – vitamin D cited 52 times – May 2021
• COVID-19 deaths 1.5X less likely if more than 40 ng of vitamin D – US VA – April 2021
• Growing consensus: COVID-19 symptoms are due to infected blood vessels - April 2021
• COVID-19 while pregnant increased many infant health problems by 1.5X – April 29, 2021   Pregnancy
• Multiple Sclerosis patients had fewer COVID-19 problems (Note: many MSers take Vitamin D) – April 30, 2021
• Problems with vaccine use during a pandemic - Dr. Bossche interview with transcript - April 22, 2021
• Vitamin D supplementation and high levels reduce COVID-19 deaths in elderly – Review April 17, 2021
• Co-Epidemic of Obesity and COVID-19 (a co-epidemic of Vitamin D not mentioned) – April 2021
• Vitamin D fights many health symptoms, including COVID-19: Dr. Mahtani video and transcript - April 2021
• COVID-19 vaccines look good in the short term, but probably not good for the long term
• COVID-19 while pregnant is not good (increased risk of dying by 22X) – April 2021   Pregnancy
• COVID-19 increased chance of death within 6 months by 1.6X, even if not hospitalized – April 2021
• Elderly nutrition and COVID-19 – systematic review July 2021
• Hospitalized children with COVID-19 and inflammation had lower vitamin D – March 2021
• Probablity of COVID-19 death increased 8X if had Periodionttitis
• COVID-19 risks reduced by Vitamin D, Magnesium, Zinc, Resveratrol, Omega-3, etc. (auto-updated)
• Long-haul COVID-19 - another hint that Vitamin D should help - Dec 2020
• 6X less risk of COVID-19 ICU if Vitamin D and Vit B12 and Mg – Jan 2021
• Vitamin D supplementation and high levels reduce COVID-19 deaths in elderly – Review April 17, 2021
• Severe childhood COVID-19 associated with Vitamin D deficiency (hospital in Turkey) – March 2021
• Kidney patients who happened to be getting high-dose Calcitriol were 9X less likely to die of COVID-19 - April 6, 2021
• Overview of reviews of COVID-19 and vitamin D, etc. – April 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
• Children with COVID-19 and low levels of Vitamin D have more severe cases – March 31, 2021
• Risk of COVID-19 death was 4.9 X higher if very low vitamin D – March 31, 2021 17th mortality observation
• Diabetes has many bidirectional links with COVID-19 – March 2021
  • Diabetes is one of the 26 health risks identified by the CDC for getting COVID-19 - ALL of which are associated with low vitamin D
• COVID-19 was 2.6X more severe if very low Vitamin D (43 studies) – meta-analysis March 26, 2021
• To protect against COVID-19, how much vitamin D – 20 to 50 ng – March 19, 2021
• COVID-19 mortality for Parkinson’s is 1 in 5, speculates that vitamin D could help - March 18, 2021
• Prefer 40 – 60 ng of Vitamin D to minimize COVID-19 – March 17, 2021
• The lower the Vitamin D, the worse the COVID-19 (600 in Turkey)– March 2021
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• COVID-19 prognostic indicators in plasma extrapolate to zero if Vitamin D is 40 to 80 ng – March 2021
• COVID public health messages 1, 2, and 3 should be - vitamin d vitamin d, vitamin d (video and transcript) - Mar 5, 2021
• COVID-19 mortality 2X higher if low Vitamin D (Mexican hospital, preprint) - March 2021
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• Chronic Fatigue Syndrome and long-haul COVID-19
  • low vitamin D, autoimmune and cytokine storms may be involved on both
• 2.1 X more COVID-19 deaths in European countries with less than 20 ng of vitamin D – March 12, 2021
• Supporting non-standard but proven ways to fight COVID-19 can result in job loss – March 2021
• 3X less likely to die of COVID-19 if good level of vitamin D (seniors in Boston)– March 8, 2021
• Low Vitamin D associated with 2.7X more severe COVID-19 – 12th MA March 5, 2021
• COVID-19 fought by Vitamin D or Heat - Drs Seheult and Patrick video - March 3, 2021
• Vitamin D Deficiency and Covid-19: Book by Drs Anderson and Grimes - July 2020
• Vitamin D recommendations for COVID-19 – Spanish Geriatrics Society – March 2021
• 250,000 FREE bottles of vitamin D to fight COVID-19 by Dr. Murray at iHerb – March 3 2021 Dr. Oz show
• Vitamin D and COVID-19 webinar - Feb 24, 2021
• Mongolia's National Vitamin D3 Program started in 2019
• COVID-19 what it is, prevention by Functional Nutrition doctor - Feb 2021
• All COVID-19 in ICU had low vitamin D, no difference in outcome if low vs very low – Feb 2021
• Low-cost Ivermectin and Vitamin D fight COVID-19 – Marik video 1 hr – Feb 18, 2021
• Low vitamin D associated with COVID-19 problems in NYC hospitals – Feb 2021
• All COVID-19 patients had low vitamin D, the lowest were more likely to die – Feb 18, 2021
• Vitamin D not help 10 days after COVID-19 symptoms - RCT March 2021
• 5X less likely to enter ICU with COVID-19 if get Calcifediol (semi-activated vitamin D) - RCT Feb 19, 2021
• Ultra-Orthodox Jews have concealing clothing, high levels of COVID-19, and ultra low Vitamin D - Feb 2021
• c19study.com/d Summary of Vitamin D and COVID studies (the following is updated automatically)
• 

• Vitamin D can prevent severe COVID-19 in Latin America too – review Feb 1, 2021
• Vitamin D and COVID-19: 1 hour simple video - Jan 31, 2021
• Higher vitamin D in a country is associated with fewer COVID-19 cases (in Asia) Feb 3, 2021 44th association
  • 
• Vitamin-D and COVID-19: time for the profession to take a stand – Jan 20, 2021
• Roll Call of Credible Experts Advocating Vitamin D for COVID-19 - Jan 26, 2021
• Call for immediate action - Fight COVID-19 with vitamin D (up to 4,000 IU) - Jan 28, 2021
• Vitamin D, Zinc, etc. look promising for COVID-19 (Holick) – Jan 25, 2021
• Heavy Smokers 2.2 X more likely to be hospitalized with COVID-19 (they typically have 10 ng less Vitamin D) Jan 25 FREE PDF
• Vitamin D plus Inositol might help pregnancies during COVID-19 – April 2021
• MATH plus protocol for COVID-19 includes Calcifediol or Vitamin D - Jan 2021
• Vitamin D supplementation fights COVID-19 – 11th meta-analysis Jan 24, 2021
• Vitamin D helps the immune system fight COVID-19 – video Jan 21, 2021
• COVID-19 2.7 X more likely to be severe if less than 8 ng of vitamin D (China) – Jan 2021
• 2.7 fewer COVID-19 hospital deaths in those having more than 30 ng of vitamin D – Mayo Jan 9, 2021
• Vitamin D Help Us Fight Infections - interview of Dr. Thakkar (transcript) Jan 20, 2021
• COVID-19 onset strongly associated with latitude in Europe (Vitamin D)– Jan 21, 2021
• France: 73 experts and 6 academies recommend vitamin D to prevent COVID-19 Jan 19, 2021
• Worse COVID-19 patients got 400,000 IU of vitamin D, deaths cut in half – Jan 14, 2021
• Vitamin D-COVID interview by Dr. Campbell of Davies (member of UK Parliament) - Jan 17, 2021
• Iranians with COVID-19 were 2.3 X more likely to die if low vitamin D – Jan 2021
• Many COVID-19 risks are associated with low vitamin D (7 studies) – Systematic Review Jan 2021
• 40 ng of Vitamin D to fight COVID 15K to 50K weekly or 100K monthly - Spanish Jan 2021
• Poor COVID-19 prognosis was 6 X more likely if low vitamin D – Jan 21, 2021
• Unraveling the roles of vitamin D status and melanin during COVID-19 (Review) Jan 11
• 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
• 3.7 X less likely to die of COVID-19 if supplemented with Vitamin D - meta-analysis Jan 5, 2021
• COVID-19 test positive 4.5 X more likely if had low vitamin D test within 4 years – Jan 6, 2021
• Don’t Let COVID-19 Patients Die With Vitamin D Deficiency - Jan 5, 2021
• Less likely to test positive for COVID-19 if higher Vitamin D – meta-analysis Jan 6, 2021
• Vitamin D reduces COVID-19 by 80 percent - anonymous meta-analysis - Jan 5, 2021
• COVID 19 Video - Drs. Seheult and Campbell - Jan 2021
• Many drugs increase ACE2 and COVID-19 (176 page review) - Dec 2020
• Italian nursing home COVID-19 – 4X less likely to die if taking Vitamin D– Dec 22, 2020
• Take 50,000 IU of Vitamin D weekly before and after COVID-19 vaccination by VItaminDWiki
• COVID-19 lung infection upsets Vitamin D genes (so more or different form of Vit D is required) - Dec 22, 2020
• COVID-19 Disease and Vitamin D: A Mini-Review – Dec 15, 2020
• French Consensus – 200,000 IU of Vitamin D if get COVID-19 – Dec 22, 2020
• Rational approach to COVID-19: 50k-100k of Vitamin D weekly – Dec 2020
• Shift workers 2X more likely to get COVID-19 (low Vitamin D) - Dec 2020
• COVID-19 plus pneumonia in ICU with low vitamin D equaled Death - Dec 2020
• Excellent on-going analysis of Vitamin D and COVID-19 publications
• Those getting high dose vitamin D were 7 X less likely to die of COVID-19 - Dec 11, 2020
• COVID-19 patients with low vitamin D had far fewer natural killer cells – Dec 2020
• COVID-19 Vitamin D: Overview of Evidence by Dr. Seheult (Video and transcript) - Dec 10, 2020
• 75 articles indicate that Vitamin D should fight COVID-19 – Evidence Review Dec 10, 2020
• COVID-19 Vitamin D: Overview by Dr. in Sri Lanka (Video and transcript) - Dec 8, 2020
• Vitamin D recommended to fight COVID-19 by 2 groups – Dec 7, 2020
• Vitamin D helps athletes while reducing their COVID-19 risk - Dec 4, 2020
• 5X more likely to test positive for COVID-19 if low vitamin D in previous 5 years (900,000 people) - Dec 4, 2020
• 5.8 X more likely to die of COVID-19 if low vitamin D - Systematic Review Dec 3, 2020
• Evidence of Vitamin D fighting COVID-19 etc. - take 4,000 IU if less than 20 ng (UK) – Dec 1, 2020
• 3.8 X higher risk of COVID-19 death if low vitamin D – Belgium Nov 25, 2020
• Hyperglycemic 2X more likely to have severe COVID-19 - Nov 2020 Diabetes
• A Medical School COVID-19 protocol includes Vitamin D for all phases – Marik Nov 2020
• Fight COVID-19 without drugs or vaccines, Vitamin D is the single most-studied way – Nov 2020
• Hospital COVID-19 observation: 7X more likely to live if more than 20 ng of vitamin D– Nov 19, 2020
• Higher vitamin D associated with fewer cases and deaths in India Nov 2020
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• COVID-19 defeated 3x faster by 420,000 IU Vitamin D nanoemulsion – RCT Nov 12, 2020
• 9X COVID-19 survival in nursing home if had 80,000 IU dose of vitamin D in previous month – Oct 2020
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• Rate of COVID-19 test positive is 40 pcnt lower if high vitamin D (192,000 people) - Holick Sept 2020
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Dr. Annweiler, an author of this study, has RCT #6

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A few web items on this study

• Reddit - with 111 comments in first 24 hours