Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2-92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79-13.42, p < 0.001 and HR 14.73, 95% CI 4.16-52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

Vitamin D Deficiency and Outcome of COVID-19 Patients.

There is still limited evidence regarding the influence of vitamin D in people with COVID-19. In this systematic review and meta-analysis, we analyze the association between vitamin D deficiency and COVID-19 severity, via an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases-Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19. We carried out a meta-analysis with random effect measures. We identified 1542 articles and selected 27. Vitamin D deficiency was not associated with a higher chance of infection by COVID-19 (OR = 1.35; 95% CI = 0.80-1.88), but we identified that severe cases of COVID-19 present 64% (OR = 1.64; 95% CI = 1.30-2.09) more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization (OR = 1.81, 95% CI = 1.41-2.21) and mortality from COVID-19 (OR = 1.82, 95% CI = 1.06-2.58). We observed a positive association between vitamin D deficiency and the severity of the disease.

Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis.

BACKGROUND: As an immune modulator, vitamin D has been implicated in the coronavirus disease-2019 (COVID-19) outcome. We aim to systematically explore the association of vitamin D serum levels with COVID-19 severity and prognosis. METHODS: The standardized mean difference (SMD) or odds ratio and 95% confidence interval (CI) were applied to estimate pooled results from six studies. The prognostic performance of vitamin D serum levels for predicting adverse outcomes with detection of the best cutoff threshold was determined by receiver operating characteristic curve analysis. Decision tree analysis by combining vitamin D levels and clinical features was applied to predict severity in COVID-19 patients. RESULTS: Mean vitamin D serum level of 376 patients, was 21.9 nmol/L (95% CI = 15.36-28.45). Significant heterogeneity was found (I2 = 99.1%, p < .001). Patients with poor prognosis (N = 150) had significantly lower serum levels of vitamin D compared with those with good prognosis (N = 161), representing an adjusted standardized mean difference of -0.58 (95% Cl = -0.83 to -0.34, p < .001). CONCLUSION: Serum vitamin D levels could be implicated in the COVID-19 prognosis. Diagnosis of vitamin D deficiency could be a helpful adjunct in assessing patients' potential of developing severe COVID-19. Appropriate preventative and/or therapeutic intervention may improve COVID-19 outcomes.

Vitamin D insufficiency as a potential culprit in critical COVID-19 patients.

As the world's attention has been riveted upon the growing COVID-19 pandemic, many researchers have written brief reports supporting the hypothesis that vitamin D deficiency is related to the incidence and severity of COVID-19. The clear common thread among the top risk groups-vitamin D deficiency-may be being overlooked because of previous overstated claims of vitamin D benefits. However, the need to decrease COVID-19 fatalities among high-risk populations is urgent. Early researchers reported three striking patterns. Firstly, the innate immune system is impaired by vitamin D deficiency, which would predispose sufferers to viral infections such as COVID-19. Vitamin D deficiency also increases the activity of the X-chromosome-linked "Renin-Angiotensin" System, making vitamin D deficient individuals (especially men) more susceptible to COVID-19's deadly "cytokine storm" (dramatic immune system overreaction). Secondly, the groups who are at highest risk for severe COVID-19 match those who are at highest risk for severe vitamin D deficiency. This includes the elderly, men, ethnic groups whose skin is naturally rich in melanin (if living outside the tropics), those who avoid sun exposure for cultural and health reasons, those who live in institutions, the obese, and/or those who suffer with hypertension, cardiovascular disease, or diabetes. And thirdly, the pattern of geographical spread of COVID-19 reflects higher population vitamin D deficiency. Both within the USA and throughout the world, COVID-19 fatality rates parallel vitamin D deficiency rates. A literature search was performed on PubMed, Google Scholar, and RSMLDS, with targeted Google searches providing additional sources. Although randomized controlled trial results may be available eventually, the correlational and causal study evidence supporting a link between vitamin D deficiency and COVID-19 risks is already so strong that it supports action. The 141 author groups writing primarily about biological plausibility detailed how vitamin D deficiency can explain every risk factor and every complication of COVID-19, but agreed that other factors are undoubtedly at work. COVID-19 was compared with dengue fever, for which oral vitamin D supplements of 4,000 IU for 10 days were significantly more effective than 1,000 IU in reducing virus replication and controlling the "cytokine storm" (dramatic immune system over-reaction) responsible for fatalities. Among the 47 original research studies summarized here, chart reviews found that serum vitamin D levels predicted COVID-19 mortality rates (16 studies) and linearly predicted COVID-19 illness severity (8 studies). Two causal modeling studies and several analyses of variance strongly supported the hypothesis that vitamin D deficiency is a causal, rather than a bystander, factor in COVID-19 outcomes. Three of the four studies whose findings opposed the hypothesis relied upon disproven assumptions. The literature review also found that prophylactically correcting possible vitamin D deficiency during the COVID-19 pandemic is extremely safe. Widely recommending 2,000 IU of vitamin D daily for all populations with limited ability to manufacture vitamin D from the sun has virtually no potential for harm and is reasonably likely to save many lives.

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A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency

Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis.

Male gender, age over 40 years, cancer, diabetes mellitus, and chronic respiratory and cardiovascular disease have each been associated with increased severity of disease, including ARDS, after SARS-CoV-2 infection. We hypothesize that nutrition might also play a role. Vitamin D (25OHD) deficiency has previously been linked to a greater susceptibility to viral infection, ARDS, and pneumonia.3,4 Since 25OHD deficiency is both highly prevalent and easily treatable and the morbidity, mortality, and costs of SARS-CoV-2 related ARDS are great, we wanted to explore whether 25OHD levels might be associated with an increased risk of the development of ARDS due to SARS-CoV-2.

W. Tormey

Papers

Vitamin d deficiency and ards after sars-cov-2 infection