- G6PD (glycose-6-phosphate dehydrogenase) deficiency may be associated with an increase risk of infection to COVID-19.1,2,3
- In vitro studies show that G6PD-deficient cells are more vulnerable to coronavirus 229E, which as a lot of similarities with novel coronavirus 2019.1
- Viral replication was significantly higher in G6PD-deficient cells2,3, and it is postulated that oxidative stress may explain the increased susceptibility of these cells to viral infection.3
- Moreover, hypoxemia related to COVID-19 infection may cause hemolysis in G6PD-deficient patients.4
- Nevertheless, data regarding COVID-19 virulence and G6PD-deficiency is lacking.
- As hydroxychloroquine is gaining popularity, special concerns are raising regarding hydroxychloroquine related hemolysis crisis and G6PD deficiency.1,2,4
- Hydroxychloroquine has oxidative properties that could decrease glutathione levels and may cause severe hemolysis in G6PD-deficient patients.1
- It is well established that chloroquine-induced hemolysis is a result of reduced G6PD enzyme activity.2
- One suspected case of severe hemolysis in a G6PD-deficient patient infected with COVID-19 and treated with hydroxychloroquine has been reported.4
- G6PD-deficiency is the most common human enzymatic disorder of the red blood cells worldwide. Therefore, if hydroxychloroquine is used for a COVID-19 infection, the authors suggest:
- To use the lowest dose possible if the patient is known for G6PD deficiency.
- To assess hemolytic biochemical markers if hydroxychloroquine is associated with new onset of anemia and proceed with G6PD-deficiency diagnostic workup as needed.
About the suspected case of severe hemolysis in a G6PD-deficient patient infected : A 68-year-old Congolese male not previously known for G6PD deficiency, known for type 2 diabetes, high blood pressure, and CKD (G2 stage) and previous history of stroke is admitted for classical respiratory symptoms of COVID-19 infection. He was started on amoxicillin/clavulanate as per hospital protocol but switch to piperacillin/tazobactam after deterioration the next day. He was transferred to ICU and required mechanical ventilation. A single dose of hydroxychloroquine was administered on day 6 as per hospital protocol. During hospitalization, a drop of hemoglobin was noted, going from 12 g/dL to 6.5 g/dL on day 6 requiring several blood transfusions. Spoliation was excluded with full digestive workup. Biochemicals signs of hemolysis with a progressive increase of total and direct bilirubin and lactate dehydrogenase was noted from day 5. Blood smear showed hemi-ghost cells and microspherocytes. Diagnosis of G6PD deficiency was confirmed with a dosage of G6PD/Total hemoglobin. Worsening hemolysis blood parameters were noted following hydroxychloroquine (day 7).
Sources:
- Al-Abdi Sameer, Al-Aamri Maryam. (April 18, 2020). G6PD deficiency in the COVID-19 pandemic: “ghost within gosth”. Hematology/Oncology and Stem Cell Therapy. https://doi.org/10.1016/j.hemonc.2020.04.002
- Kassi A.N., Papavassiliou K.A., Papavassiliou A.G. (April 5, 2020). G6PD and chloroquine: Selecting the treatment against SARS-CoV-2? Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/jcmm.15312
- We Y.H., Tseng C.P., Cheng M.L., Ho H.Y., Shih S.., Chiu D.T.Y. (March 15, 2008). Glucose-6-Phosphate Dehydrogenase Deficiency Enhances Human Coronavirus 299E Infection. The Journal of Infectious Diseases, Infection Diseases Society of America. https://doi.org/10.1086/528377
- Beauverd Y., Adam Y., Assouline B., Samii K. (April 23, 2020). COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency. European Journal of Haematology. https://doi.org/10.1111/ejh.13432