Jim and his wife Cynthia are old friends and long time patients in my office.  Last week, Jim called the office to report Cynthia was not feeling well, and where should she go for a Corona Virus test?  I explained to Jim the testing is unreliable, and we no longer use the testing for Corona Virus.  There is nothing in medicine worse than an unreliable test.

Boosting the Immune System with vitamin D3

Instead, our approach is to boost the immune system with Vitamin D and a few other things such as Zinc, (which Cynthia was already taking).  Cynthia had no fever, and only mild symptoms which could be related to almost anything.  Rather than immediately go for the big guns, the Z-pack and Hydroxychloroquine, I suggested boosting her immune system with additional Vitamin D, C,  and A.   We also started her on Chinese Skullcap (Baicalin) , an excellent anti-viral botanical.  Since it was after hours, I invited Jim to stop over at the house to pick up everything.  After all, Jim and Cynthia were old friends, so I was happy to share from my personal supply.  On the way out the door, Jim said “thanks for the vitamins, but do you have any experience treating COVID-19 ?”   This is the typical type of question I usually get, so I am prepared for it.

Testing for Vitamin D and Vitamin C

I then explained to Jim that we come into contact with hundreds of viruses on a regular basis.  They are floating around in the air.  We do not get sick because our immune systems defend us from viral disease.

So, our approach to Corona Virus is the same as all the other viruses, we boost our immune systems with supplements.   Vitamin D3 is probably the most important one.  In my office, we  routinely test for Vitamin D levels on every patient, and give vitamin D supplements for everyone found vitamin D deficient.  Similarly, we also test for and supplement with Vitamin C (ascorbate).   Perhaps this is the explanation for why our office practice has had no patient require hospitalization for upper respiratory viral disease over the last 8 months of the “pandemic”.  NO ONE !!!  The following day, Jim calls in the report Cynthia is feeling much better.

Anti-viral benefits of Vitamin D3 has been extensively studied over the years. (1-24)  In my opinion, the main benefit is on the immune system as an immuno-modulator which prevents the dreaded “cytokine storm” responsible for admission to the intensive care unit.  In one randomized  study by Dr. Castillo on corona virus patients hospitalized in Spain, the administration of vitamin D3 reduced admission to the intensive care unit  from 50% to 2% !!!  There were no deaths in the Vitamin D treated patients !!!    Dr Castillo writes:

“Based on a pilot study, oral calcifediol (Vitamin D3) may be the most promising approach.” (16-17)

Supplementing Vitamin D3 Levels in Nursing Homes

A number of studies have shown that the thousands of elderly nursing home deaths from corona virus were in patients with vitamin D deficiency.  Simply by testing for and supplementing with vitamin D3 in this population would have been preventive.(2)(30-35)

Unreliability of Coronavirus PCR Testing

Jim had another question that was coming up frequently.  His cousin Betty who was 40 years old just arrived from New York and was staying with them for  few weeks.   Betty had recovered from a corona virus infection back in March along with everyone else in New York and tested positive back in March.   Betty recovered uneventfully with only mild upper respiratory symptoms, and has been feeling fine since then. However, just to be on the safe side, Betty repeated the Corona Virus PCR test last week, and it was still positive !!  Jim wanted to know what to do with Betty’s positive test.  I explained to Jim that this was a “false positive test”, meaning the test is detecting dead viral genetic material with no infectious capability.  Recent study by Dr. Lu shows that up to 14% of Corona Virus patients continue to test positive after recovering from the viral illness, and are no longer infectious.  This is one of the reasons the testing is unreliable. Dr Lu writes:

“Re-positive SARS-CoV-2 cases do not appear to be caused by active reinfection and were identified in ~14% of discharged cases.”(27)

Masks and Social Distancing for the Kids ??

The next question Jim asked was what about masks for the kids? Why do they need to wear masks at school ??  According to the Toronto Hospital for Sick Children Expert Report, kids should be allowed to attend school as normally as possible without masks or social distancing.  Kids are at very low risk for corona virus says Dr Scott Atlas who is on the White House Corona Virus Advisory Panel.  Dr Atlas agrees with the Toronto Hospital Report, and advises that kids do not need to wear masks or social distance at school.  Children are not at risk, and have asymptomatic or only mildly symptomatic bouts with corona virus.

If We Have Vitamin D, Hydroxychloroquine and Zinc, Why Do We Need A Vaccine ?

The next question Jim asked me is, “if we can boost the immune system with Vitamin D, and take anti-virals such as Zinc, Hydroxychloroquine, Z-Pack (azithromycin) and Chines Skullcap (Baical), transforming corona virus into a mild illness (like in children) , then why do we need a vaccine?”     Why do we need a rushed vaccine with no testing for efficacy, and only limited safety testing, with vaccine manufacturers who deny any responsible if you are injured by their vaccine product?  Unlike all other manufacturers in the U.S., you can not sue the vaccine maker if you are left paralyzed or dead after vaccine injection.  This is because of the 1986 Vaccine Act of Congress which made vaccine makers exempt from product liability.  When people ask me about the corona virus vaccine, my response is to say: “You First” !!

Conclusion:  Effective viral prevention and treatment involves boosting the immune system with Vitamin D3.  Instead of spending billions of dollars on research and development for a corona virus vaccine, we could be using Vitamin D3 testing and supplementation for the population instead.  Hastily rolling out an untested, questionable vaccine product is a recipe for disaster, especially when we already have excellent immune boosting anti-viral strategies.  The last time the government did this during the 1976 Swine Flu epidemic was a complete disaster, causing hundreds of cases of Guillan Barre syndrome (paralysis) and terminated the vaccine program.(29)

Articles With related Interest

Hydroxychloroquine Efficacy Against Corona Virus

Effective Early Treatment for Corona Virus

Vitamin D Prevents Flu

Stop Vitamin D, Are You Joking ?

Jeffrey Dach MD
7450 Griffin Road Suite 180/190
Davie, Florida 33314
954-792-4663

Link and References

Header Image courtesy of Wikimedia Commons

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231123/
Grant, William B., et al. “Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths.” Nutrients 12.4 (2020): 988.
The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

2) McCartney, Daniel M., and D. G. Byrne. “Optimisation of vitamin D status for enhanced Immuno-protection against Covid-19.” Ir Med J 113.4 (2020): 58.

Vitamin D deficiency (serum 25(OH)D<50nmol/l) is common in Ireland, particularly amongst older adults, hospital inpatients and nursing home residents. Vitamin D deficiency is associated with increased risk of acute viral respiratory infection and community acquired pneumonia, with several molecular mechanisms proposed to explain this association. Vitamin D supplementation has also been shown to reduce the risk of respiratory infection.

Vitamin D and Covid-19

Correction of vitamin D deficiency is thought to suppress CD26, a putative adhesion molecule for Covid-19 host cell invasion. Vitamin D may also attenuate interferon gamma (IFNγ) and interleukin-6 (IL-6) inflammatory responses, both potent predictors of poorer outcome in critically-ill ventilated patients including those with Covid-19.
Vitamin D Requirements

Irish adults require 25-30μg/d of vitamin D3, an intake not achievable by diet alone, to reliably maintain serum 25(OH)D levels >50nmol/l. Supplementation with doses up to 100μg/d has been shown to be safe for adults, and many agencies and expert groups now advocate supplementation in older adults, albeit at lower levels than this.

Conclusions and Recommendations
Vitamin D deficiency is common and may contribute to increased risk of respiratory infection including Covid-19. We recommend that all older adults, hospital inpatients, nursing home residents and other vulnerable groups (e.g. those with diabetes mellitus or compromised immune function, those with darker skin, vegetarians and vegans, those who are overweight or obese, smokers and healthcare workers) be urgently supplemented with 20-50μg/d of vitamin D to enhance their resistance to Covid-19, and that this advice be quickly extended to the general adult population.

3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264531/
Rhodes, Jonathan M., et al. “low population mortality from COVID‐19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity.” Alimentary pharmacology & therapeutics 51.12 (2020): 1434-1437.
There are considerable experimental data showing that vitamin D is important in regulating and suppressing the inflammatory cytokine response of respiratory epithelial cells and macrophages to various pathogens including respiratory viruses. 9 Evidence that vitamin D might protect against infection is modest but it is important to note that the hypothesis is not that vitamin D would protect against SARS‐CoV‐2 infection but that it could be very important in preventing the cytokine storm and subsequent acute respiratory distress syndrome that is commonly the cause of mortality. 10

4) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216123/
Ebadi, Maryam, and Aldo J. Montano-Loza. “Perspective: improving vitamin D status in the management of COVID-19.” European Journal of Clinical Nutrition (2020): 1-4.
Vitamin D is a secosteroid that has a wide spectrum of immunomodulatory, anti-inflammatory antifibrotic, and antioxidant actions. Expression of inflammatory cytokine [e.g., IL-1α, IL-1β, tumor necrosis factor-α] was inhibited by vitamin D and its insufficiency was associated with overexpression of Th1 cytokines [4]. We have recently found that severe vitamin D deficiency (<25 nmol/L) is associated with disease progression and increased mortality in patients with autoimmune liver diseases [5]. This attribute has generated interest in vitamin D as a pathogenic factor that can be measured, monitored, and manipulated [6].

5) Laird, E., J. Rhodes, and Rose Anne Kenny. “Vitamin D and inflammation: potential implications for severity of COVID-19.” Ir Med J 113.5 (2020): 81.
Background
Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways.

We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality.
Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation.
Results
Counter-intuitively, lower latitude and typically ‘sunny’ countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman’s Rank Correlation.
Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.

6) Alipio, Mark. “Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19).” Available at SSRN 3571484 (2020).
In this paper, a multinomial logistic regression was used to predict clinical outcomes of patients infected with COVID-2019 based on 25-hydroxyvitamin D [25(OH)D] levels, the barometer for Vitamin D status. A retrospective multicentre study of 212 cases with laboratory-confirmed infection of SARS-CoV-2 was conducted. Data pertaining to clinical features and serum 25(OH)D levels were extracted from the medical records. For statistical analysis, Mann-Whitney U and χ² testswere usedto compare differences in the clinical outcomes. Multinomial logistic regression was used to explore the association between serum 25(OH)D level and clinical outcomes of the cases. Frequency and percentage were used for categorical variables. Mean was used for continuous variables. A p-value below 0.01 was considered statistically significant. Of the 212 cases of COVID-2019, majority had ordinary clinical outcome. Mean serum 25(OH)D level was 23.8 ng/ml. Serum 25(OH)D level was lowest in critical cases, but highest in mild cases. Serum 25(OH)D levels were statistically significant among clinical outcomes. Majority had insufficient Vitamin D status, most of them were not severe. Vitamin D status is significantly associated with clinical outcomes. A multinomial logistic regression analysis reported that for each standard deviation increase in serum 25(OH)D, the odds of having a mild clinical outcome rather than a severe outcome wereincreasedapproximately 7.94 times (OR=0.126, p<0.001) while interestingly, the odds of having a mild clinical outcome rather than a critical outcome were increased approximately 19.61 times (OR=0.051, p<0.001). The results suggest that an increase in serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while a decrease in serum 25(OH)D level in the body could worsen clinical outcomes of COVID-2019 patients. In conclusion, this study provides substantial information to clinicians and health policy-makers. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with COVID-2019. Further research should conduct randomized controlled trials and large population studies to evaluate this recommendation.

7) Rhodes, Jonathan M., et al. “Perspective: Vitamin D deficiency and COVID‐19 severity–plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1).” Journal of internal medicine (2020).

Background: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a ‘cytokine storm’ and lung failure. Vitamin D deficiency has been postulated as a determinant of severity.
Objectives: To review the evidence relevant to vitamin D and COVID-19.
Methods: Narrative review.
Results: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury.
Conclusions: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.

8) Liu, Guoqiang, Tianpei Hong, and Jin Yang. “A Single Large Dose of Vitamin D Could be Used as a Means of Coronavirus Disease 2019 Prevention and Treatment.” Drug Design, Development and Therapy 14 (2020): 3429-3434.
Abstract: we hypothesize that a single large dose of vitamin D (Vit D) could be an option for trial in COVID-19. Vit D deficiency or insufficiency is very common in the general population as well as in patients with COVID-19. It has been shown that low Vit D level is associated with viral infection, and Vit D supplementation is beneficial for people infected with viruses, such as HIV and hepatitis C virus. Although COVID-19 is a respiratory disease, the morbidity and mortality of this disease are driven by coagulopathy. Clinical studies have shown that Vit D can exert anticoagulant effects. Vit D, a lipid-soluble vitamin, can be administered as a draught. Vit D supplementation is safe and has rare toxic events. In addition, the cost of Vit D is fairly low. Based on these observations, we speculate that a single dose of 300,000 IU Vit D may have a role in the prevention and treatment of COVID-19.

9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398646/
Martineau, Adrian R., and Nita G. Forouhi. “Vitamin D for COVID-19: a case to answer?.” The Lancet. Diabetes & Endocrinology (2020).
Interest in a potential role for vitamin D in the prevention or treatment of acute respiratory infections dates back to the 1930s, when cod liver oil was investigated as a means to reduce industrial absenteeism due to the common cold. Meta-analyses of randomised controlled trials conducted from 2007–20 reveal protective effects of vitamin D against acute respiratory infections, albeit these effects were of modest size and with substantial heterogeneity.1 The striking overlap between risk factors for severe COVID-19 and vitamin D deficiency, including obesity, older age, and Black or Asian ethnic origin, has led some researchers to hypothesise that vitamin D supplementation could hold promise as a preventive or therapeutic agent for COVID-19.

10) https://www.maturitas.org/article/S0378-5122(20)30346-7/fulltext
Shakoor, Hira, et al. “Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: could they help against COVID-19?.” Maturitas (2020).
COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. There are currently no effective anti-SARS-CoV-2 viral drugs or vaccines. COVID-19 disproportionately affects the elderly, both directly, and through a number of significant age-related comorbidities. Undoubtedly, nutrition is a key determinant of maintaining good health. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19. In this paper, evidence surrounding the role of these dietary components in immunity as well as their specific effect in COVID-19 patients are discussed. In addition, how supplementation of these nutrients may be used as therapeutic modalities potentially to decrease the morbidity and mortality rates of patients with COVID-19 is discussed.
A number of nutrients have been associated with improved outcomes for patients with COVID-19.
Vitamin D is associated with both decreased rates of infection and improved outcomes for patients.
Vitamin C may shorten the course of the disease and decrease the severity of the symptoms.
Vitamin E, zinc and selenium are known to assist with recovery from viral infection, and may have efficacy in COVID-19.

11) https://link.springer.com/article/10.1007/s40520-020-01570-8?fbclid=IwAR1-rI7BA9jSdBEafWcf7vX5lHLnC9mMC3Ov2QiX3YfAjKxP8NXaM8_ORrw&error=cookies_not_supported&code=ca51802a-7bbb-4b29-8793-9f386b715d39
Ilie, Petre Cristian, Simina Stefanescu, and Lee Smith. “The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality.” Aging Clinical and Experimental Research (2020): 1-4.
WHO declared SARS-CoV-2 a global pandemic.

of ICU admission and deaths.
Results:  Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95%CI 0.002-0.17).

Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95%CI: 0.003-0.25).

Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.
Conclusion  Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

17) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289092/
Quesada-Gomez, Jose Manuel, Marta Entrenas Castillo, and Roger Bouillon. “Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166.” The Journal of Steroid Biochemistry and Molecular Biology (2020): 105719.

The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro) coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach.

18) Benskin, Linda. “A Basic Review of the Preliminary Evidence that Covid-19 Risk and Severity is Increased in Vitamin D Deficiency.” Benskin LL (2020).

19) Brenner, Hermann, Bernd Holleczek, and Ben Schöttker. “Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?.” Nutrients 12.8 (2020): 2488.
Abstract: The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D3 supplementation might help to reduce respiratory disease mortality. We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30–50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50–75 years from Saarland, Germany.

Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3–3.2) and 3.0 (1.8–5.2) overall,
4.3 (1.3–14.4) and 8.5 (2.4–30.1) among women, and 1.9 (1.1–3.2) and 2.3 (1.1–4.4) among men. Overall, 41% (95% confidence interval: 20–58%) of respiratory disease mortality was statistically attributable to
vitamin D insufficiency or deficiency.

Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.

20) Lau, Frank H., et al. “Vitamin D insufficiency is prevalent in severe COVID-19.” medRxiv (2020).

VDI was defined as serum 25OHD < 30 ng/mL.10
Results Twenty COVID-19 patients with serum 25OHD levels were identified; 13 (65.0%) required ICU admission. Overall, few significant differences were identified between ICU and floor patients (Table 1) but statistical analysis was limited by the small number of subjects. Lactate dehydrogenase on admission was significantly higher among ICU patients (441.8 vs. 223.0, p=0.001), consistent with previous reports. No patients were diagnosed with stroke, myocardial infarction, or pulmonary embolus. Two patients (10%) died during the study period.

Among ICU subjects, 11 (84.6%) had VDI, vs. 4 (57.1%) of floor subjects.

Strikingly, 100% of ICU patients less than 75 years old had VDI (n=11; Table 2). Among these,64.6% (n=7) had critically low 25OHD (<20 ng/mL) and three had <10 ng/mL. The sepsis-induced coagulopathy score (SIC) was calculable for 8 subjects; 62.5% (n=5) had SIC ≥ 4. Suppressed immune function was prevalent: 92.3% (n=12) were lymphocytopenic, and 9 were profoundly so (absolute lymphocyte count ≤ 0.4 10^3/uL; normal range 1.10-5.00).

The baseline prevalence of VDI amongst ICU patients is 30-40%.12 In this study, we found that 84.6% of COVID-19 ICU patients had VDI, vs. 57.1% of floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. We also found that 62.5% had CAC, and 92.3% had lymphopenia.

Given these data, we hypothesize that VDI enhances COVID-19 severity via 1) its prothrombotic effects and 2) its derangement of the immune response

21) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274230/
Meltzer, David O., et al. “Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence.” medRxiv (2020).
Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19.
Design: Retrospective cohort study Setting: University of Chicago Medicine
Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased).
Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed.
Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age (RR(age<50)=1.05,p<0.021; RR(age≥50)=1.02,p<0.064)), non-white race (RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient (not-deficient/treatment-not-decreased), with

predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group.

Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19.

Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.

 

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19 vs 20 ???????????

22) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404739/
Merzon, Eugene, et al. “Low plasma 25 (OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study.” The FEBS journal (2020).
The study population included the 14,000 members of Leumit Health Services who were tested for COVID‐19 infection from February 1st to April 30th 2020, and who had at least one previous blood test for plasma 25(OH)D level. “Suboptimal” or “low” plasma 25(OH)D level was defined as plasma 25‐hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL.
Results Of 7,807 individuals, 782 (10.1%) were COVID‐19‐positive, and 7,025 (89.9%) COVID‐19‐negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID‐19 [19.00 ng/mL (95% confidence interval [CI] 18.41‐19.59) vs. 20.55 (95% CI 20.32‐20.78)].

Univariate analysis demonstrated an association between low plasma 25(OH) D level and increased likelihood of COVID‐19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24‐2.01, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [crude OR of 2.09 (95% CI 1.01‐ 4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID‐19 infection [1.45 (95% CI 1.08‐1.95, p<0.001)], and of hospitalization due to the SARS‐CoV‐2 virus [1.95 (95% CI 0.98‐4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low‐medium socioeconomic status were also positively associated with the risk of COVID‐19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID‐19.
Conclusion Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization.
Keywords: Vitamin D, COVID‐19, risk of infection, low plasma 25(OH) vitamin D level, Israeli population study

23) Jesenak, Milos, et al. “Immune parameters and COVID-19 infection-associations with clinical severity and diseases prognosis.” Frontiers in cellular and infection microbiology 10 (2020): 364.

24) Sparavigna, Amelia Carolina. “Vitamin D for Covid-19?.”

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