Glucose-6-phosphate dehydrogenase deficiency associated hemolysis in COVID-19 patients treated with hydroxychloroquine/chloroquine: New case reports coming out.

Afra TP et al comment our recent report entitled: “acute hemolysis by hydroxychloroquine (HCQ) was observed in G6PD-deficient patient with severe COVID-19 related lung injury” [1,2]. Afra et al. underlight ”confounding factors and inconsistencies” in our conclusion, linking acute drop in Hb in COVID-19 patient with suspected G6PD and HCQ treatment. We respectfully disagree with comments from Afra et al. Our case report was the first one of a series, linking G6PD deficiency with HCQ/CQ treatment for COVID19 infection such as Kuiper ME et al. or Beauverd Y et al. or Maillart et al. [3–5]. In our case, we observed an acute drop of Hb values associated with the appearance of hemoglo-binuria and abnormalities in red cell morphology at the blood smear within 48 h after patient hospital admission and the introduction of HCQ treatment. Our patient was transfused and HCQ was withdrawn with stabilization of Hb values. Thus, this was not a spontaneous re-covery of Hb values as suspected by Afra et al. (see Fig. 1 in De Fran-ceschi L et al 2020) [2]. In addition, hemoglobinuria is a hallmark of intravascular hemolysis, which characterizes drug induced acute he-molysis in G6PD patients [6]. Otherwise, drug induced hemolytic an-emia in patients with healthy red cells is general an extravascular he-molysis without hemoglobinuria. Italy is an endemic area for G6PD deficiency [6]. Our patient was suspected for G6PD deficiency based on previous hemolytic events re-corded in patient history. To fully answer the question raised by Afra et al., we have evaluated G6PD activity in our patients at 8 weeks after hospital discharge. As expected we found G6PD deficiency with normal complete blood count analysis and normal reticulocyte count (43.500 retics/uL). Collectively our results and the post-recovery determination of G6PD support the link between acute hemolysis and HCQ/CQ treatment in COVID-19 patients