Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity

BACKGROUND: Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes. METHODS: We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses. RESULTS: We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level <20â¯ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9â¯ng/ml (95% CI [-9.5, -2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000â¯IU/day, from one week to 12â¯months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (ORâ¯=â¯0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000â¯IU/day, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes. CONCLUSION: While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.

The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis.

OBJECTIVES: Vitamin D deficiency was previously correlated with incidence and severity of coronavirus disease 2019 (COVID-19). We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) level on admission and radiologic stage and outcome of COVID-19 pneumonia. METHODS: A retrospective observational trial was done on 186 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals hospitalized from March 1, 2020, to April 7, 2020, with combined chest computed tomography (CT) and 25(OH)D measurement on admission. Multivariate regression analysis was performed to study if vitamin D deficiency (25(OH)D <20 ng/mL) correlates with survival independently of confounding comorbidities. RESULTS: Of the patients with COVID-19, 59% were vitamin D deficient on admission: 47% of females and 67% of males. In particular, male patients with COVID-19 showed progressively lower 25(OH)D with advancing radiologic stage, with deficiency rates increasing from 55% in stage 1 to 74% in stage 3. Vitamin D deficiency on admission was not confounded by age, ethnicity, chronic lung disease, coronary artery disease/hypertension, or diabetes and was associated with mortality (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.30-11.55), independent of age (OR, 1.09; 95% CI, 1.03-1.14), chronic lung disease (OR, 3.61; 95% CI, 1.18-11.09), and extent of lung damage expressed by chest CT severity score (OR, 1.12; 95% CI, 1.01-1.25). CONCLUSIONS: Low 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality.

Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality.

Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis.

Background: Coronavirus disease (COVID-19) is a respiratory and systemic disorder caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or novel Coronavirus (nCoV). To date, there is no proven curative treatment for this virus; as a result, prevention remains to be the best strategy to combat coronavirus infection (COVID-19). Vitamin D deficiency (VDD) has been proposed to play a role in coronavirus infection (COVID-19). However, there is no conclusive evidence on its impact on COVID-19 infection. Therefore, the present review aimed to summarize the available evidence regarding the association between Vitamin D levels and the risk of COVID-19 infection. Methods: A systematic literature search of databases (PUBMED/MEDLINE, Cochrane/Wiley library, Scopus, and SciELO) were conducted from May 15, 2020, to December 20, 2020. Studies that assessed the effect of vitamin D level on COVID-19/SARS-2 infection were considered for the review. The qualities of the included studies were evaluated using the JBI tools. Meta-analysis with a random-effects model was conducted and odds ratio with their 95%CI were reported. This systematic review and meta-analysis are reported according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline. Results: The electronic and supplementary searches for this review yielded 318 records from which, only 14 of them met the inclusion criteria. The qualitative synthesis indicated that vitamin D deficient individuals were at higher risk of COVID-19 infection as compared to vitamin D sufficient patients. The pooled analysis showed that individuals with Vitamin-D deficiency were 80% more likely to acquire COVID-19 infection as compared to those who have sufficient Vitamin D levels (OR = 1.80; 95%CI: 1.72, 1.88). Begg's test also revealed that there was no significant publication bias between the studies (P = 0.764). The subgroup analysis revealed that the risk of acquiring COVID-19 infection was relatively higher in the case-control study design (OR = 1.81). Conclusions: In conclusion, low serum 25 (OH) Vitamin-D level was significantly associated with a higher risk of COVID-19 infection. The limited currently available data suggest that sufficient Vitamin D level in serum is associated with a significantly decreased risk of COVID-19 infection.

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The Impact of Vitamin D Level on COVID-19 Infection: Systematic Review and Meta-Analysis.

As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level...

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients.

Prognostic value of hypothyroidism in patients undergoing intensity‐modulated radiation therapy for nasopharyngeal carcinoma

BACKGROUND
To evaluate the application value of urinary prostatic exosomal protein (PSEP) in the treatment of chronic prostatitis (CP).


METHODS
We evaluated 174 patients with chronic prostatitis (44 cases of NIH-II, 65 cases of NIH-IIIa, and 65 cases of NIH-IIIb) who had obvious symptoms of chronic prostatitis syndrome and met the diagnostic criteria of National Institutes of Health Prostatitis from May 2018 to February 2021. They were also evaluated according to the clinical treatment's effect after six weeks of treatment. Urine samples of CP patients were collected before treatment and after six weeks of treatment, and the level of PSEP in the urine samples of all patients, before and after treatment, was detected by the ELISA method to evaluate the application value of PSEP in the end of CP curative effect.


RESULTS
After six weeks of treatment, the total CPSI score of CP patients decreased significantly, compared to patients before treatment. After six weeks of treatment, the PSEP content in the patients' urine was compared to before treatment. The PSEP levels of CP subgroups decreased significantly (p < 0.05): NIH-II group (1.55 ± 1.39 ng/mL vs. 3.09 ± 2.66 ng/mL); NIH-IIIa group (1.68 ± 1.06 ng/mL vs. 3.34 ± 2.69 ng/mL); and NIH-IIIb group (1.57 ± 1.17 ng/mL vs. 3.14 ± 2.81 ng/mL).


CONCLUSIONS
The concentration of PSEP in the urine of CP patients has a good application value for evaluating clinical treatment's effect on chronic prostatitis, and its concentration level may affect the development and outcome of prostatitis.

Study on the Application Value of the Content of Prostatic Exosomal Protein in the Treatment of Chronic Prostatitis.

Purpose SARS-CoV-2 is extremely infectious, and the incidence of nosocomial infection is conceivably high. We aimed to develop and validate a nomogram to assist monitoring nosocomial SARS-CoV-2 infection in hospitalized patients. Patients and Methods There were 437 COVID-19 hospitalized cases and 420 negative inpatients enrolled from two hospitals in Hubei province, China. We compared the demographic and clinical characteristics of participants between the two groups. Then, LASSO regression and logistic regression were applied to build a nomogram for SARS-CoV-2 infection prediction in the development cohort. Our nomogram was assessed by area under the curve (AUC), calibration curve, decision curve (DCA) and clinical impact curve analysis (CICA). Results After LASSO regression filtration, eleven laboratory indicators were correlated with SARS-CoV-2 infection. Then, we integrated these features and constructed a nomogram, which showed a high AUC 0.863 (95% CI: 0.834–0.892) in the development cohort with a sensitivity of 80.41% and specificity of 77.38% and 0.813 (95% CI: 0.760–0.866) in validation cohort with a sensitivity of 82.98% and specificity of 70.43%. The calibration plot displayed that the predicted outcomes were in good concordance with the actual observations. DCA and CICA further showed a larger clinical net benefit. Conclusion We constructed and validated a nomogram that integrated eleven laboratory indexes to assist monitoring of nosocomial SARS-CoV-2 infection in hospitalized patients. Our nomogram is remarkably informative for clinical practice, which will be helpful for preventing SARS-CoV-2 further transmission in hospital and avoiding nosocomial infection.

https://www.dovepress.com/getfile.php?fileID=78672

Leping Ning

Papers

Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study.

Prognostic value of hypothyroidism in patients undergoing intensity‐modulated radiation therapy for nasopharyngeal carcinoma

Study on the Application Value of the Content of Prostatic Exosomal Protein in the Treatment of Chronic Prostatitis.

Development and Validation of a Nomogram to Assist Monitoring Nosocomial SARS-CoV-2 Infection of Hospitalized Patients