Interaction between G6PD deficiency and COVID-19
The severity of COVID-19 is influenced by genetic variants of G6PD in humans, which is related to an impaired immune response [111]. It has been predicted that COVID-19 will spread more widely in areas or countries with a high prevalence of G6PD deficiency. This concern poses a serious challenge to treat COVID-19 in G6PD-deficient patients. Severe G6PD deficiency is associated with an altered immune response, including NET formation, inflammasome activation, and bactericidal activity as well as an antiviral response [9–11,42,85,95,110]. Hence, G6PD deficiency presents a challenge during the COVID-19 pandemic.
Several factors can influence the clinical severity in patients with COVID-19. Age is associated with elevated morbidity and mortality in patients with COVID-19 [112]. The elderly with COVID-19 (32%) have higher mortality rates compared with the middle-aged and the young [113]. The elderly with coexisting conditions, such as diabetes, hypertension, and obesity increase their mortality risk five-fold [114]. Oxidative stress and aging go hand in hand during coronavirus infection. Aging not only affects the immune response, but also induces a pro-inflammatory state. Aged-animals infected with SARS-CoV display more severe lesions and an increased pro-inflammatory response than their young counterparts [115]. This indicates that the age-associated accumulation of oxidative stress and a reduced antioxidative defense can worsen viral infections [116]. It is speculated that G6PD-deficient variants enhance the clinical severity of COVID-19. Hence, in the elderly with COVID-19, those with G6PD deficiency may become more anaemic than those with the normal activity of G6PD [117,118].
One of risk factors leading to a higher incidence of COVID-19 is ethnicity. African-Americans have a higher incidence of COVID-19 [119]. G6PD-deficient African Americans have higher levels of GSSG and lipid peroxide in the blood compared to G6PD-normal African Americans [120]. Co-supplementation of vitamin D and L-cysteine has been recommended for the increased oxidative stress and an impaired immune response in SARS-CoV-2 infection for in G6PD-deficient African-Americans [121].