RESUMEN
Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.
Asunto(s)
Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Deficiencia de Glucosafosfato Deshidrogenasa/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adulto , Antirreumáticos/uso terapéutico , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/virología , Esquema de Medicación , Ferritinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/virología , Humanos , Hidroxicloroquina/uso terapéutico , Inflamación/prevención & control , Masculino , Pandemias , Neumonía Viral/sangre , Neumonía Viral/complicaciones , Neumonía Viral/virología , SARS-CoV-2 , Resultado del TratamientoRESUMEN
We report a case of intravascular hemolysis and methemoglobinemia, precipitated by severe acute respiratory syndrome coronavirus 2 infection, in a patient with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Clinicians should be aware of this complication of coronavirus disease as a cause of error in pulse oximetry and a potential risk for drug-induced hemolysis.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/virología , Metahemoglobinemia/virología , Neumonía Viral/complicaciones , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/virología , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Humanos , Masculino , Metahemoglobinemia/sangre , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/virología , SARS-CoV-2RESUMEN
Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH:GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with N-acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.
Asunto(s)
Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/enzimología , Infecciones por Enterovirus/etiología , Glucosafosfato Deshidrogenasa/metabolismo , Antioxidantes/farmacología , Secuencia de Bases , Células Cultivadas , Efecto Citopatogénico Viral , ADN Viral/genética , Enterovirus Humano A/genética , Enterovirus Humano A/fisiología , Infecciones por Enterovirus/prevención & control , Infecciones por Enterovirus/virología , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Deficiencia de Glucosafosfato Deshidrogenasa/virología , Glutatión , Disulfuro de Glutatión/metabolismo , Humanos , Estrés Oxidativo , Ensayo de Placa Viral , Virulencia , Replicación ViralRESUMEN
The host cellular environment is a key determinant of pathogen infectivity. Viral gene expression and viral particle production of glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD-knockdown cells were much higher than their counterparts when human coronavirus (HCoV) 229E was applied at 0.1 multiplicity of infection. These phenomena were correlated with increased oxidant production. Accordingly, ectopic expression of G6PD in G6PD-deficient cells or addition of antioxidant (such as alpha-lipoic acid) to G6PD-knockdown cells attenuated the increased susceptibility to HCoV 229E infection. All experimental data indicated that oxidative stress in host cells is an important factor in HCoV 229E infectivity.