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1.
Pharmacogenomics J ; 21(6): 649-656, 2021 12.
Article in English | MEDLINE | ID: covidwho-1526064

ABSTRACT

Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identified nine variants, of which four are potentially deleterious to G6PD function, and one (rs1050828) that is known to cause G6PD deficiency. We supplemented data for the rs1050828 variant with genotype array data from over 11,000 Africans. Although this variant is common in Africans overall, large allele frequency differences exist between sub-populations. African sub-populations in the same country can show significant differences in allele frequency (e.g. 16.0% in Tsonga vs 0.8% in Xhosa, both in South Africa, p = 2.4 × 10-3). The high prevalence of variants in the G6PD gene found in this analysis suggests that it may be a significant interaction factor in clinical trials of chloroquine and hydroxychloroquine for treatment of COVID-19 in Africans.


Subject(s)
COVID-19/drug therapy , Chloroquine/adverse effects , Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/genetics , Hydroxychloroquine/adverse effects , Africa South of the Sahara/epidemiology , COVID-19/epidemiology , COVID-19/genetics , Databases, Genetic , Genetic Variation/genetics , Glucosephosphate Dehydrogenase Deficiency/drug therapy , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Humans , Mutation, Missense/genetics , Risk Factors
2.
Nucleosides Nucleotides Nucleic Acids ; 40(5): 505-517, 2021.
Article in English | MEDLINE | ID: covidwho-1132307

ABSTRACT

COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. On the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19 and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.


Subject(s)
COVID-19/genetics , Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase/genetics , Thrombosis/genetics , Adult , COVID-19/blood , COVID-19/complications , COVID-19/virology , Glucosephosphate Dehydrogenase Deficiency/blood , Glucosephosphate Dehydrogenase Deficiency/complications , Glucosephosphate Dehydrogenase Deficiency/pathology , Hemolysis/physiology , Humans , Male , Risk Factors , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Thrombosis/blood , Thrombosis/etiology , Thrombosis/virology
3.
Free Radic Biol Med ; 161: 84-91, 2020 12.
Article in English | MEDLINE | ID: covidwho-1023568

ABSTRACT

There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.


Subject(s)
COVID-19/pathology , Glucosephosphate Dehydrogenase Deficiency/genetics , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Vitamin D Deficiency/genetics , African Americans/statistics & numerical data , COVID-19/mortality , Cytokine Release Syndrome/pathology , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase Deficiency/metabolism , Glutathione/metabolism , Humans , SARS-CoV-2 , Vitamin D/analogs & derivatives , Vitamin D/metabolism
4.
Free Radic Res ; 55(4): 364-374, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1010202

ABSTRACT

The COVID-19 pandemic has so far affected more than 45 million people and has caused over 1 million deaths worldwide. Infection with SARS-CoV-2, the pathogenic agent, which is associated with an imbalanced redox status, causes hyperinflammation and a cytokine storm, leading to cell death. Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals may experience a hemolytic crisis after being exposed to oxidants or infection. Individuals with G6PD deficiency are more susceptible to coronavirus infection than individuals with normally functioning G6PD. An altered immune response to viral infections is found in individuals with G6PD deficiency. Evidence indicates that G6PD deficiency is a predisposing factor of COVID-19.


Subject(s)
COVID-19 , Glucosephosphate Dehydrogenase Deficiency , SARS-CoV-2/physiology , Virus Diseases , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , Disease Susceptibility , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase/metabolism , Glucosephosphate Dehydrogenase Deficiency/complications , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Glucosephosphate Dehydrogenase Deficiency/genetics , Glucosephosphate Dehydrogenase Deficiency/metabolism , Homeostasis/physiology , Humans , Oxidation-Reduction , Pandemics , Virus Diseases/epidemiology , Virus Diseases/genetics , Virus Diseases/metabolism
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