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Contribution of vitamin D3 and thiols status to the outcome of COVID-19 disease in Italian pediatric and adult patients

D’Alessandro et al., Scientific Reports, doi:10.1038/s41598-023-29519-7
Feb 2023  
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Retrospective 173 patients in Italy showing significantly lower glutathione levels and high prevalence of vitamin D deficiency in COVID-19 patients, and lower levels of glutathione and vitamin D associated with mortality.
Acetaminophen (paracetamol) has been shown to lower glutathione levels Burgunder, and authors note that the widespread use of acetaminophen for COVID-19 may be detrimental:
"It has been recently shown that paracetamol (PAC), extensively adopted in the therapy of COVID-19 disease, could be a link between GSH consumption and the severe COVID-19 illness. In fact, as discussed above, therapeutic doses of PAC can lower GSH levels, thus impairing the endogenous antioxidant defenses. Furthermore, an illuminating commentary suggests that is important than prescription of PAC should be endorsed with caution in sensitive populations with scarce GSH levels, such as the elderly. It was recently demonstrated that a parallel intake of N-acetyl-cysteine (NAC) could be useful in order to correct the GSH deficiency in this population. In addition, it has clearly evidenced that GSH levels directly influence VD status. Moreover, before the COVID-19 outbreak, a serious VD deficiency in the general population was reported. We could therefore speculate that the current situation resembles a pandemic in the pandemic and that the generous use of paracetamol could exacerbate this scenario leading to a pandemic GSH deficiency."
This study includes acetaminophen and vitamin D.
D’Alessandro et al., 13 Feb 2023, retrospective, Italy, peer-reviewed, 12 authors, study period March 2020 - May 2020.
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Contribution of vitamin D3 and thiols status to the outcome of COVID-19 disease in Italian pediatric and adult patients
D’alessandro Annamaria, Ciavardelli Domenico, Pastore Anna, Lupisella Santina, Cristofaro Rosa Carmela, Di Felice Giovina, Roberta Salierno, Infante Marco, De Stefano Alberto, Onetti Muda Andrea, Morello Maria, Porzio Ottavia
Scientific Reports, doi:10.1038/s41598-023-29519-7
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), was declared a global pandemic by the World Health Organization (WHO) on March 2020, causing unprecedented disease with million deaths across the globe, mostly adults. Indeed, children accounted for only a few percent of cases. Italy was the first Western country struck by the COVID-19 epidemic. Increasing age, which is one of the principal risk factors for COVID-19 mortality, is associated with declined glutathione (GSH) levels. Over the last decade, several studies demonstrated that both vitamin D (VD) and GSH have immunomodulatory properties. To verify the association between VD, GSH and the outcome of COVID-19 disease, we conducted a multicenter retrospective study in 35 children and 128 adult patients with COVID-19. Our study demonstrated a hypovitaminosis D in COVID-19 patients, suggesting a possible role of low VD status in increasing the risk of COVID-19 infection and subsequent hospitalization. In addition, we find a thiol disturbance with a GSH depletion associated to the disease severity. In children, who fortunately survived, both VD and GSH levels at admission were higher than in adults, suggesting that lower VD and thiols levels upon admission may be a modifiable risk factor for adverse outcomes and mortality in hospitalized patients with COVID-19. The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SAR-SCoV-2), was first reported in December 2019 in Wuhan, a city in China. COVID-19 was then declared by the World Health Organization (WHO) a global pandemic (March 11, 2020). Italy was the first Western country struck by the COVID-19 pandemic. COVID-19 continues to cause unprecedented disease with medical, social, and economic challenges across the globe. As of 6th June 2022, more than 531 million cases have been confirmed worldwide, with over 6.3 million deaths (https:// coron avirus. jhu. edu/ map. html), mostly adults. Indeed, for much of the past 2 years, children accounted for only a few percent of cases, less than 5% in most areas, with hospitalization rates below 2% and mortality rate under 1%. Several risk factors, including age, hypertension, ischemic heart disease, diabetes, and chronic respiratory disease have been identified to be associated with a high Cytokine determinations. Chemiluminescence method was used to measure IL-6 serum levels (reference range: 0-50 pg/mL; IMMULITE 2000 instrument, Siemens, Milan, Italy). Enzyme-linked immunosorbent assay (ELISA) technique was used to analyze TNF-α serum levels (reference range: 0-12.4 pg/mL; DRG, International Instruments GmbH, Marburg, Germany). Other laboratory assays. An infectious disease specialist made the initial diagnosis of COVID-19 based on clinical symptoms (cough, fever, and dyspnea), and confirmed by positive SARS-CoV-2 nasopharyngeal swab qPCR test. Hematological and biochemical parameters were measured on blood, serum, or plasma samples collected at admission. Although the two Hospitals uses different analytical instrumentation, the analytical methods are identical. An automated hematological analyzer was used to measure the white blood cell (WBC) count. We also calculated the NLR, a marker of systemic inflammation 13 . An immunoturbidimetric method were used to measure the serum levels of CRP. Serum levels of ferritin and PCT were measured using chemiluminescence methods. Serum LDH levels were assayed by an UV assay. Plasma fibrinogen was determined by using clotting methods, whereas D-dimer levels were measured by immunoturbidimetric methods. Statistical analysis. The GraphPad Prism 9.0 software were used to calculate descriptive statistics data, including mean and standard deviation (SD), median and percentiles (GraphPad..
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