Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: The COVID-19 pandemic represents one of the world's most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. METHODS: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. RESULTS: We identified 78 bibliographic citations. After the reviewers' screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34-0.72) and 0.28 (0.20-0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. DISCUSSION: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.

Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients.

The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker predicting the prognosis of several diseases. We aimed to assess its role as a predictor of mortality or admission to the intensive care unit in COVID-19 patients. We retrospectively evaluated a cohort of 411 patients with COVID-19 infection. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of patients with COVID-19 were compared. The median age of our sample was 72 years (interquartile range: 70-75); 237 were males. Hypertension, diabetes and ischemic heart disease were the most common comorbidities. The study population was subdivided into three groups according to NLR tertiles. Third-tertile patients were older, showing significantly higher levels of inflammatory markers; 133 patients (32%) died during hospitalization, 81 of whom belonged to the third tertile; 79 patients (19%) were admitted to ICU. NLR showed the largest area under the curve (0.772), with the highest specificity (71.9%) and sensitivity (72.9%), whereas CRP showed lower sensitivity (60.2%) but slightly higher specificity (72.3%). Comparisons between NLR and CRP ROC curves were significantly different (p = 0.0173). Cox regression models showed that the association between NLR and death was not weakened after adjustment for confounders. Comparisons of ROC curves showed no significant differences between NLR, PLR, and CRP. Cox regression analysis showed that NLR predicted the risk of admission to ICU independently of demographic characteristics and comorbidities (HR: 3.9597, p < 0.0001). These findings provide evidence that NLR is an independent predictor of mortality and a worse outcome in COVID-19 patients and may help identify high-risk individuals with COVID-19 infection at admission.

An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19.

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.

Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.

Immunological Characteristics of Non-Intensive Care Hospitalized COVID-19 Patients: A Preliminary Report.

The outbreak of coronavirus disease 2019 (COVID-19) is posing a threat to global health. This disease has different clinical manifestations and different outcomes. The immune response to the novel 2019 coronavirus is complex and involves both innate and adaptive immunity. In this context, cell-mediated immunity plays a vital role in effective immunity against SARS-CoV-2. Significant differences have been observed when comparing severe and non-severe patients. Since these immunological characteristics have not been fully elucidated, we aimed to use cluster analysis to investigate the immune cell patterns in patients with COVID-19 who required hospitalization but not intensive care. We identified four clusters of different immunological patterns, the worst being characterized by total lymphocytes, T helper lymphocytes CD4+ (CD4+), T cytotoxic lymphocytes CD8+ (CD8+) and natural killer (NK) cells below the normal range, together with natural killer lymphocyte granzyme < 50% (NK granzyme+) and antibody-secreting plasma cells (ASCs) equal to 0 with fatal outcomes. In the worst group, 50% of patients died in the intensive care unit. Moreover, a negative trend was found among four groups regarding total lymphocytes, CD4+, CD8+ and B lymphocytes (p < 0.001, p < 0.005, p < 0.000, p < 0.044, respectively). This detailed analysis of immune changes may have prognostic value. It may provide a new perspective for identifying subsets of COVID-19 patients and selecting novel prospective treatment strategies. Notwithstanding these results, this is a preliminary report with a small sample size, and our data may not be generalizable. Further cohort studies with larger samples are necessary to quantify the prognostic value's weight, according to immunological changes in COVID-19 patients, for predicting prognoses and realizing improvements in clinical conditions.

Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry.

Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patients, 932 (19.8%) had a diagnosis of COPD. Patients with COPD had more hospitalization, a significant overt cognitive impairment, a clinically significant disability and more depression in comparison with non-COPD subjects. COPD patients took more drugs, both at admission, in-hospital stay, discharge and 3-month and 1-year follow-up. 14 comorbidities were more frequent in COPD patients. Cerebrovascular disease was an independent predictor of in-hospital mortality. At 3-month follow-up, male sex and hepatic cirrhosis were independently associated with mortality. ICS-LABA therapy was predictor of mortality at in-hospital, 3-month and 1-year follow-up. This analysis showed the severity of impact of COPD and its comorbidities in the real life of internal medicine and geriatric wards.