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Covid 19Glucose-6-Phosphate Dehydrogenase DeficiencyCase ReportHydroxychloroquineThe coronavirus disease 2019 (COVID-19) is until today a global health emergency. In an immense efort, efective drugs against COVID-19 are searched and intensive researches on possible repurposing of antiviral agents are performed. Since chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro anti- COVID-19 activities, the potential efect of CQ/ HCQ to treat and/or prevent COVID-19 infection has caused global attention. However, concern regarding possible hemolysis in G6PD-defcient COVID-19 patients exists and for this reason, the association between HCQ and G6PD defciency (G6PDD) is back in the limelight. This study aims to answer the question raised by Mastroianni et al. “Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Defcient Patients with COVID-19?”, reporting all cases of HCQ in G6PD defcient COVID-19 patients published on PubMed (pubmed.ncbi.nlm.nih.gov), in addition to the Mastroianni’s patient. In our opinion, after an accurate revision of these cases and responding the question raised by Mastroianni et al., we believe that it is difcult to reach a fnal verdict about the defnitive role of HCQ in these patients. The COVID-19 pandemic has reopened attention on HCQ use and G6PDD. G6PD status is extremely important in modulating the level of reactive oxygen species and many cellular immune responses such as enhanced production of the pro-infammatory cytokine and infammasome activation. Since these processes are involved in COVID-19 infection, acute hemolytic anemia, a severe complication of the G6PDD, can occur in these patients. In this context, the role of HCQ, usually efective, safe, and well tolerated in G6PD defcient patients, must be redefned in these patients with COVID-19.As consequence, answering the question: “Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Defcient Patients with COVID-19?”, we state that it is risky to believe that HCQ may be an “innocent bystander” in G6PD-defcient COVID-19 patients