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1.
Clin Nutr ; 40(5): 3462-3469, 2021 05.
Article in English | MEDLINE | ID: covidwho-967936

ABSTRACT

BACKGROUND & AIMS: Iron is an essential trace element to almost all organism, and the delicate balance between host defend system and viral proliferation plays an important role in infective conditions. While the association of the iron metabolism with the prognosis of COVID-19 remains poorly understood. We aimed to estimate the associations of systemic iron metabolism parameters with the severity and risks of adverse outcomes in COVID-19. METHODS: In this retrospective cohort study, we included 158 confirmed COVID-19 patients in Tongji Hospital, Wuhan, China (27 January to 5 April, 2020). Demographic data, comorbidities, laboratory examinations, treatments, and clinical outcomes were all collected. Multivariable Poisson regression was used to estimate the association of iron parameter levels with the severity and risks of adverse outcomes in COVID-19 patients. RESULTS: We identified 60 (38%) severe cases in 158 COVID-19 patients. The median age was 63 years (interquartile range [IQR]: 54-73) and the median length of hospital stay was 28 days (IQR: 17-40). After adjusting for age, sex, IL-6, and pre-existing comorbidities, all iron parameters were associated with the severity of COVID-19 with adjusted risk ratio of 0.42 [95% CI: 0.22-0.83], 4.38 [95% CI: 1.86-10.33], 0.19 [95% CI: 0.08-0.48], and 0.25 [95% CI: 0.10-0.58] for serum iron, ferritin, transferrin, and total iron-binding capacity, respectively. These iron indices were also related to the risk of ARDS, coagulopathy, acute cardiac injury, acute liver injury, and acute kidney injury in COVID-19 patients and high cytokine concentrations. CONCLUSIONS: Patients with low serum iron status likely suffered from severe condition and multiple-organ injury in COVID-19. The iron metabolism parameters might be risk factors and clinical biomarkers for COVID-19 prognosis.


Subject(s)
COVID-19/blood , Ferritins/metabolism , Iron/metabolism , Severity of Illness Index , Transferrin/metabolism , Aged , COVID-19/epidemiology , COVID-19/physiopathology , China/epidemiology , Cohort Studies , Cytokines , Female , Humans , Male , Middle Aged , Receptors, Transferrin/metabolism , Retrospective Studies , SARS-CoV-2
2.
Restor Neurol Neurosci ; 38(4): 343-354, 2020.
Article in English | MEDLINE | ID: covidwho-621099

ABSTRACT

Covid-19 is the acute illness caused by SARS-CoV-2 with initial clinical symptoms such as cough, fever, malaise, headache, and anosmia. After entry into cells, corona viruses (CoV) activate aryl hydrocarbon receptors (AhRs) by an indoleamine 2,3-dioxygenase (IDO1)-independent mechanism, bypassing the IDO1-kynurenine-AhR pathway. The IDO1-kynurenine-AhR signaling pathway is used by multiple viral, microbial and parasitic pathogens to activate AhRs and to establish infections. AhRs enhance their own activity through an IDO1-AhR-IDO1 positive feedback loop prolonging activation induced by pathogens. Direct activation of AhRs by CoV induces immediate and simultaneous up-regulation of diverse AhR-dependent downstream effectors, and this, in turn, results in a "Systemic AhR Activation Syndrome" (SAAS) consisting of inflammation, thromboembolism, and fibrosis, culminating in multiple organ injuries, and death. Activation of AhRs by CoV may lead to diverse sets of phenotypic disease pictures depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs. We hypothesize that elimination of factors known to up-regulate AhRs, or implementation of measures known to down-regulate AhRs, should decrease severity of infection. Although therapies selectively down-regulating both AhR and IDO1 are currently lacking, medications in clinical use such as dexamethasone may down-regulate both AhR and IDO1 genes, as calcitriol/vitamin D3 may down-regulate the AhR gene, and tocopherol/vitamin E may down-regulate the IDO1 gene. Supplementation of calcitriol should therefore be subjected to epidemiological studies and tested in prospective trials for prevention of CoV infections, as should tocopherol, whereas dexamethasone could be tried in interventional trials. Because lack of physical exercise activates AhRs via the IDO1-kynurenine-AhR signaling pathway increasing risk of infection, physical exercise should be encouraged during quarantines and stay-at-home orders during pandemic outbreaks. Understanding which factors affect gene expression of both AhR and IDO1 may help in designing therapies to prevent and treat humans suffering from Covid-19.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/physiopathology , Indoleamine-Pyrrole 2,3,-Dioxygenase/physiology , Pandemics , Pneumonia, Viral/physiopathology , Receptors, Aryl Hydrocarbon/physiology , Air Pollutants/adverse effects , COVID-19 , Calcitriol/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Dexamethasone/therapeutic use , Exercise , Feedback, Physiological , Female , Fibrosis/etiology , Gene Expression Regulation/drug effects , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Inflammation/etiology , Kynurenine/physiology , Male , Molecular Targeted Therapy , Multiple Organ Failure/etiology , Obstetric Labor, Premature/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Receptors, Aryl Hydrocarbon/biosynthesis , Receptors, Aryl Hydrocarbon/genetics , SARS-CoV-2 , Sensation Disorders/etiology , Signal Transduction/drug effects , Signal Transduction/physiology , Thromboembolism/etiology , Tocopherols/therapeutic use , COVID-19 Drug Treatment
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