Subject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsABSTRACT
Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.
Subject(s)
COVID-19/blood , COVID-19/diagnosis , Polymorphism, Genetic , Vitamin D Deficiency/blood , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D/genetics , Aged , Biomarkers , Cholestanetriol 26-Monooxygenase/genetics , Cytochrome P450 Family 2/genetics , Female , Genetic Predisposition to Disease , Hospitalization , Humans , Male , Middle Aged , Oxidoreductases Acting on CH-CH Group Donors/genetics , Portugal/epidemiology , Prevalence , Severity of Illness Index , Vesicular Transport Proteins/genetics , Vitamin D-Binding Protein/genetics , Vitamin D3 24-Hydroxylase/geneticsSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsSubject(s)
Biological Products , COVID-19 , Vitamin D Deficiency , Child , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsABSTRACT
What is Known? ⢠Vitamin D has multiple roles in the immune system that can modulate the body reaction to an infection ⢠Vitamin D binding protein (DBP) is the key transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites What is New? ⢠Lower 25 OH vitamin D levels were associated with higher inflammation markers, suggesting an important role of vitamin D in the clinical course of COVID-19 in children and adolescents probably by regulating the systemic inflammatory response ⢠Further studies are warranted to investigate the possible causal association of DBP levels and polymorphism with vitamin D status (total and bioavailable vitamin D) in COVID-19 patients.
Subject(s)
Biological Products , COVID-19 , Adolescent , Child , Humans , SARS-CoV-2 , Vitamin D , Vitamin D-Binding Protein/geneticsSubject(s)
Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , Complement C3/genetics , Coronavirus Infections/mortality , Haptoglobins/genetics , Hemochromatosis Protein/genetics , Humans , INDEL Mutation/genetics , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/mortality , Polymorphism, Genetic/genetics , Prevalence , SARS-CoV-2 , Vitamin D-Binding Protein/geneticsABSTRACT
The SARS-CoV-2 pandemic has become one of the most serious health concerns globally. Although multiple vaccines have recently been approved for the prevention of coronavirus disease 2019 (COVID-19), an effective treatment is still lacking. Our knowledge of the pathogenicity of this virus is still incomplete. Studies have revealed that viral factors such as the viral load, duration of exposure to the virus, and viral mutations are important variables in COVID-19 outcome. Furthermore, host factors, including age, health condition, co-morbidities, and genetic background, might also be involved in clinical manifestations and infection outcome. This review focuses on the importance of variations in the host genetic background and pathogenesis of SARS-CoV-2. We will discuss the significance of polymorphisms in the ACE-2, TMPRSS2, vitamin D receptor, vitamin D binding protein, CD147, glucose-regulated protein 78 kDa, dipeptidyl peptidase-4 (DPP4), neuropilin-1, heme oxygenase, apolipoprotein L1, vitamin K epoxide reductase complex 1 (VKORC1), and immune system genes for the clinical outcome of COVID-19.
Subject(s)
COVID-19/genetics , ABO Blood-Group System/genetics , Angiotensin-Converting Enzyme 2/genetics , Apolipoprotein L1/genetics , Basigin/genetics , COVID-19/epidemiology , COVID-19/therapy , Dipeptidyl Peptidase 4/genetics , Endoplasmic Reticulum Chaperone BiP , Heat-Shock Proteins/genetics , Heme Oxygenase-1/genetics , Humans , Immunity/genetics , Neuropilin-1/genetics , Patient Outcome Assessment , Polymorphism, Genetic , Receptors, Calcitriol/genetics , SARS-CoV-2 , Serine Endopeptidases/genetics , Vitamin D-Binding Protein/genetics , Vitamin K Epoxide Reductases/geneticsABSTRACT
Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has given rise to emerging respiratory infections with pandemic diffusion. The vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels participate in various clinical conditions. The main goal of this study was to evaluate if there was any association between the DBP gene polymorphism at rs7041 and rs4588 loci and the prevalence of COVID-19 and its mortality rates caused among populations of 10 countries including Turkey. Positive significant correlations were found between the prevalence (per million) and mortality rates (per million), and GT genotype (P < .05) while there was a negative significant correlation between prevalence (per million) and mortality rates (per million), and TT genotype at rs7041 locus among all populations (P < .05). However, no significant correlation was found at rs4588 locus. GT genotype was found to confer this susceptibility to the populations of Germany, Mexico, Italy, Czech, and Turkey. The variations in the prevalence of COVID-19 and its mortality rates among countries may be explained by Vitamin D metabolism differed by the DBP polymorphisms of rs7041 and rs4588.
Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Polymorphism, Single Nucleotide , Vitamin D-Binding Protein/genetics , COVID-19/genetics , Genetic Predisposition to Disease , Genotype , Humans , Prevalence , Vitamin D/blood , Vitamin D-Binding Protein/metabolismSubject(s)
COVID-19 , Macrophage-Activating Factors/immunology , Vitamin D-Binding Protein/immunology , Vitamin D , COVID-19/immunology , COVID-19/mortality , Humans , Immunologic Factors/blood , Immunologic Factors/metabolism , Mortality , Polymorphism, Single Nucleotide , Prognosis , Protective Factors , SARS-CoV-2 , Vitamin D/blood , Vitamin D/metabolism , Vitamin D-Binding Protein/genetics , Vitamin D-Binding Protein/metabolismSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/genetics , VitaminsSubject(s)
COVID-19 , Vitamin D Deficiency , Adult , Hospitals , Humans , Morbidity , SARS-CoV-2 , Vitamin D , Vitamin D Deficiency/genetics , Vitamin D-Binding Protein/geneticsSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , Lung , Retrospective Studies , SARS-CoV-2 , Vitamin D , Vitamin D-Binding Protein/geneticsSubject(s)
COVID-19 , Vitamin D Deficiency , Humans , SARS-CoV-2 , Vitamin D , Vitamin D-Binding Protein/geneticsABSTRACT
It's since December 2019 that Corona virus disease (COVID-19) has emerged to be the global issue of concern. A "pandemic"; this is what WHO has declared about the COVID-19 outbreak on March 3rd, 2020. Vitamin D and its deficiency have recently been claimed to be one of the potential factors affecting COVID-19 risks and outcomes [1]. As Selberstein et al., has recently discussed the effect of vitamin D deficiency, and the role of vitamin D supplementation in COVID-19 patients [2], I'd believe that vitamin D binding protein (DBP) is maybe also involved. A closer look on DBP and its action on regulating the circulatory vitamin D levels, its polymorphisms and their impact on COVID-19 prevalence and mortality, will be briefly discussed.