Assessing the Operational Feasibility of Integrating Point-of-Care G6PD Testing into Plasmodium vivax Malaria Management in Vietnam.

Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination.

Glucose-6-Phosphate Dehydrogenase (G6PD) Measurement Using Biosensors by Community-Based Village Malaria Workers and Hospital Laboratory Staff in Cambodia: A Quantitative Study.

Vivax malaria can relapse after an initial infection due to dormant liver stages of the parasite. Radical cure can prevent relapses but requires the measurement of glucose-6-phosphate dehydrogenase enzyme (G6PD) activity to identify G6PD-deficient patients at risk of drug-induced haemolysis. In the absence of reliable G6PD testing, vivax patients are denied radical curative treatment in many places, including rural Cambodia. A novel Biosensor, 'G6PD Standard' (SD Biosensor, Republic of Korea; Biosensor), can measure G6PD activity at the point of care. The objectives of this study were to compare the G6PD activity readings using Biosensors by village malaria workers (VMWs) and hospital-based laboratory technicians (LTs), and to compare the G6PD deficiency categorization recommended by the Biosensor manufacturer with categories derived from a locally estimated adjusted male median (AMM) in Kravanh district, Cambodia. Participants were enrolled between 2021 and 2022 in western Cambodia. Each of the 28 VMWs and 5 LTs received a Biosensor and standardized training on its use. The G6PD activities of febrile patients identified in the community were measured by VMWs; in a subset, a second reading was done by LTs. All participants were tested for malaria by rapid diagnostic test (RDT). The adjusted male median (AMM) was calculated from all RDT-negative participants and defined as 100% G6PD activity. VMWs measured activities in 1344 participants. Of that total, 1327 (98.7%) readings were included in the analysis, and 68 of these had a positive RDT result. We calculated 100% activity as 6.4 U/gHb (interquartile range: 4.5 to 7.8); 9.9% (124/1259) of RDT-negative participants had G6PD activities below 30%, 15.2% (191/1259) had activities between 30% and 70%, and 75.0% (944/1259) had activities greater than 70%. Repeat measurements among 114 participants showed a significant correlation of G6PD readings (rs = 0.784, p < 0.001) between VMWs and LTs. Based on the manufacturer's recommendations, 285 participants (21.5%) had less than 30% activity; however, based on the AMM, 132 participants (10.0%) had less than 30% activity. The G6PD measurements by VMWs and LTs were similar. With the provisions of training, supervision, and monitoring, VMWs could play an important role in the management of vivax malaria, which is critical for the rapid elimination of malaria regionally. Definitions of deficiency based on the manufacturer's recommendations and the population-specific AMM differed significantly, which may warrant revision of these recommendations.

The relationship of serum copper and zinc levels with oxidative stress markers and other laboratory parameters in COVID-19 patients Serum copper and zinc levels with coronavirus disease 2019

Aim: Serum Copper (Cu) and Zinc (Zn) levels can be associated with novel coronavirus disease 2019 (COVID-19). However, the correlation of serum Cu and Zn levels with biochemistry, hormones, and coagulation parameters has not been fully revealed. This study aims to determine serum Cu and Zn levels and their relationships with other laboratory parameters in the acute phase of COVID-19. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 116 people: 53 healthy and 63 SARS-CoV-2-positives seriously ill. All laboratory data were retrospectively scanned from patient files at the hospital information system. Result(s): It was found that serum Cu, G6PD and TAS levels decreased, Zn TOS and OSI levels increased when COVID-19 patients were compared with healthy individuals. There is a positive correlation between serum Cu level and AST in COVID-19 patients, and a negative correlation between total bilirubin and LDH. There is a negative correlation between serum Zn levels and direct bilirubin, CRP, and procalcitonin. Discussion(s): Many studies have been reported showing that both Cu and Zn have antiviral effects against COVID-19. Although our data support these studies, it has been revealed that serum Cu and Zn levels were correlated with AST, direct/total bilirubin, LDH, CRP, and prolactin.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Co-Occurring Hemolysis and Methemoglobinemia After COVID-19 Infection in Patient With G6PD Deficiency.

Hemolytic anemia and methemoglobinemia are known complications in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. They can be elicited by various oxidative stressors. Here we report a case of an adult with the first episode of G6PD deficiency associated hemolysis and methemoglobinemia after acquiring COVID-19 infection, who had no recent exposure to oxidative drugs or fava beans. A 52-year-old gentleman known to have myocardial bridging on aspirin and beta-blocker, with no other medical illnesses, developed anemia symptoms, jaundice, and hypoxia after contracting COVID-19 infection. Further laboratory work revealed non-immune hemolytic anemia, methemoglobinemia, and a positive G6PD screen test. He was treated conservatively with a blood transfusion, and his oxygen saturation improved thereafter. With the widespread COVID-19 infection and its morbidity worldwide, it is crucial to consider methemoglobinemia in the differential diagnosis of hypoxia. Testing for G6PD is an essential next step in such cases, as starting methylene blue in G6PD deficiency can worsen hemolysis. Apart from COVID-19, there is no other identified trigger for the acute event in this patient. It is not known whether COVID-19 infection alone is enough to result in G6PD deficiency-associated hemolysis and methemoglobinemia simultaneously.

G6PD deficiency-does it alter the course of COVID-19 infections?

Despite the existence of well-founded data around the relationship between reactive oxygen species (ROS) and glucose-6-phosphate dehydrogenase (G6PD), current research around G6PD-deficient patients with viral infections, and limitations as a result of their condition, are inadequate. Here, we analyze existing data around immunological risks, complications, and consequences of this disease, particularly in relation to COVID-19 infections and treatment. The relationship between G6PD deficiency and elevated ROS leading to increased viral load suggests that these patients may confer heightened infectivity. Additionally, worsened prognoses and more severe complications of infection may be realized in class I G6PD-deficient individuals. Though more research is demanded on the topic, preliminary studies suggest that antioxidative therapy which reduces ROS levels in these patients could prove beneficial in the treatment of viral infections in G6PD-deficient individuals.

Hematologic Outcomes of COVID-19 Patients with and without G6PD Deficiency: A Comparative Study.

INTRODUCTION: Patients with multiple comorbidities who have coronavirus disease 2019 (COVID-19) have high morbidity and mortality. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to have an enhanced effect on coronavirus in an earlier study. METHODS: We conducted this comparative observational study to evaluate the effects of COVID-19 disease on G6PD deficiency based on the hematologic parameters, COVID-19-related hospitalizations, and mortality in the state of Qatar between January 2020 and May 2020 at four designated COVID-19 facilities. We identified 41 patients with G6PD deficiency who had documented COVID-19 infection. We compared the results with 241 patients with COVID-19 infection who tested negative for G6PD deficiency.: Results: Comparing the COVID-19 positive G6PD deficient with COVID-19 positive G6PD normal activity showed that G6PD normal group had higher white blood cell count (WBC), absolute neutrophil count (ANC), lymphocytes, eosinophils, and monocytes counts versus the G6PD deficient group (p < 0.001). CONCLUSIONS: When compared with COVID-19 patients with normal G6PD, patients with COVID-19 infection and G6PD deficiency had lower total WBC, ANC, lymphocyte, monocyte, and eosinophil counts. However, no evidence of increased hemolysis, thrombosis, morbidity, or mortality was observed in COVID-19 patients with G6PD deficiency.

Haematology audit of 801 COVID-19 patients' basics and beyond- Prospective observational study.

Background and Objective: COVID-19 has become a major health concern since 2020. Its clinical presentation varies from asymptomatic cases to cases with respiratory failure needing ICU management. It has created a huge burden on limited health care resources. We need better understanding of the pathogenesis and interplay between virus and other factors which decide outcome. We seek biomarkers to predict severe illness to offer better triaging of patients to provide hospital-based care to the patients at risk of severe illness. Material and Methods: We took 801 consecutive RT-PCR-positive COVID cases coming to our center. Their hematological work-up, such as complete blood count, peripheral smear, reticulocyte count, and G6PD activity, was tested. The pattern of hematological abnormalities was assessed across disease severity groups to identify predictors of severe illness from basic investigation. Also, the interplay between iron deficiency and possible hemoglobinopathy trait and COVID was explored. Results Discussion and Conclusion: We found old age, male gender, diabetes, neutrophilia, lymphopenia, monocytopenia, and eosinopenia at presentation to be associated with moderate to severe illness and may help in triaging with other inflammatory and radiological parameters. We found thrombocytosis rather than thrombocytopenia as a predictor of severe illness. Our preliminary findings suggest the need to explore the protective role of hemoglobinopathy traits and iron deficiency against severe COVID illness.

The relationship of serum copper and zinc levels with oxidative stress markers and other laboratory parameters in COVID-19 patients

Aim: Serum Copper (Cu) and Zinc (Zn) levels can be associated with novel coronavirus disease 2019 (COVID-19). However, the correlation of serum Cu and Zn levels with biochemistry, hormones, and coagulation parameters has not been fully revealed. This study aims to determine serum Cu and Zn levels and their relationships with other laboratory parameters in the acute phase of COVID-19. Material and Methods: This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 116 people: 53 healthy and 63 SARS-CoV-2-positives seriously ill. All laboratory data were retrospectively scanned from patient files at the hospital information system. Results: It was found that serum Cu, G6PD and TAS levels decreased, Zn TOS and OSI levels increased when COVID-19 patients were compared with healthy individuals. There is a positive correlation between serum Cu level and AST in COVID-19 patients, and a negative correlation between total bilirubin and LDH. There is a negative correlation between serum Zn levels and direct bilirubin, CRP, and procalcitonin. Discussion: Many studies have been reported showing that both Cu and Zn have antiviral effects against COVID-19. Although our data support these studies, it has been revealed that serum Cu and Zn levels were correlated with AST, direct/total bilirubin, LDH, CRP, and prolactin.

Infections in G6PD-Deficient Hospitalized Patients-Prevalence, Risk Factors, and Related Mortality.

G6PD deficiency is a genetic disease that weakens the immune system and renders affected individuals susceptible to infections. In the Sultanate of Oman resides a high number of recorded G6PD cases due to widespread consanguineous marriage, which may reach 25% of the population. We studied the infection patterns and risk factors for mortality to provide antimicrobial stewardship recommendations for these patients. After obtaining ethical approval, a registry of recorded cases was consulted retrospectively to include G6PD-deficient adult patients admitted to Suhar hospital over 5 years with microbiologically confirmed infections. Patient demographics, health-related information, infection causes, treatment, and clinical outcomes were studied. Data were analyzed to describe infection patterns and risk factors. Several variables, including underlying comorbidities and hospitalization details, such as length of stay, admission to critical care unit, blood transfusion, or exposure to an invasive procedure, were statistically associated with the acquisition of multidrug-resistant and hospital-acquired infections. Meanwhile, these infections were associated with a high mortality rate (28%), significantly associated with the patient's health status and earlier exposure to antimicrobial treatment due to previous bacterial infection. The high prevalence of G6PD deficiency among the Omani population should alert practitioners to take early action when dealing with such cases during infection that requires hospitalization. Strict infection control measures, Gram-negative empiric coverage, hospital discharge as early as possible, and potent targeted antimicrobial therapy in this patient population can ameliorate the treatment outcomes and should be emphasized by the antimicrobial stewardship team.

G6PD deficiency: imbalance of functional dichotomy contributing to the severity of COVID-19.

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients.

COVID-19 in G6PD-deficient Patients, Oxidative Stress, and Neuropathology.

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that regulates energy metabolism mainly through the pentose phosphate pathway (PPP). It is well known that this enzyme participates in the antioxidant/oxidant balance via the synthesis of energy-rich molecules: nicotinamide adenine dinucleotide phosphate reduced (NADPH), the reduced form of flavin adenine dinucleotide (FADH) and glutathione (GSH), controlling reactive oxygen species generation. Coronavirus disease 19 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health problem that has caused approximately 4.5 million deaths since December 2019. Concerning the role of G6PD in COVID-19 development, it is known from the existing literature that G6PD-deficient patients infected with SARS-CoV-2 are more susceptible to thrombosis and hemolysis, suggesting that G6PD deficiency facilitates infection by SARS-CoV-2. Concerning G6PD and neuropathology, it has been observed that deficiency of this enzyme is also present with an increase in oxidative markers. Concerning the role of G6PD and the neurological manifestations of COVID-19, it has been reported that the enzymatic deficiency in patients infected with SARSCoV- 2 exacerbates the disease, and, in some clinical reports, an increase in hemolysis and thrombosis was observed when patients were treated with hydroxychloroquine (OH-CQ), a drug with oxidative properties. In the present work, we summarize the evidence of the role of G6PD in COVID- 19 and its possible role in the generation of oxidative stress and glucose metabolism deficits, and inflammation present in this respiratory disease and its progression including neurological manifestations.

Occurrence of Methemoglobinemia due to COVID-19: A Case Report.

Methemoglobinemia (MetHb) is a rare, life-threatening condition that occurs when the body is exposed to oxidative stress. It is typically corrected through the glucose-6-phosphate dehydrogenase (G6PD)-dependent shunt. G6PD deficiency is the most common enzymatic deficiency worldwide. This genetic disorder makes patients susceptible to oxidative stress and reduces the expected life span of erythrocytes (red blood cells (RBCs)) among other cells. G6PD deficiency is asymptomatic in most cases unless exogenous stressors are introduced, whether they are dietary, iatrogenic, or infections, such as the highly transmissible serotype of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report a case of an 11-year-old male with known insulin-dependent diabetes mellitus (IDDM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, who was found to develop methemoglobinemia after being infected by the SARS-CoV-2 virus. The direct effects of COVID-19 on children were reported to be lower than on adults. However, the effects of COVID-19 on children with comorbidities, such as G6PD deficiency in our patient, are understood only to a minimal extent. Moreover, identifying cases of G6PD deficiency prior to initiating treatment with methylene blue, hydroxychloroquine (HCQ), or other contraindicated agents is essential to prevent further deterioration in symptoms.

Management of children with glucose-6-phosphate dehydrogenase deficiency presenting with acute haemolytic crisis during the SARs-COV-2 pandemic.

BACKGROUND AND OBJECTIVES: Shortage of blood during the severe acute respiratory syndrome-COV-2 (SARs-COV-2) pandemic impacted transfusion practice. The primary aim of the study is to assess management of acute haemolytic crisis (AHC) in glucose-6-phosphate dehydrogenase(G6PD)- deficient children during SARs-COV-2 pandemic, and then to assess blood donation situation and the role of telemedicine in management. METHODS: Assessment of G6PD-deficient children attending the Emergency Department (ER) with AHC from 1 March 2020 for 5 months in comparison to same period in the previous 2 years, in three paediatric haematology centres. AHC cases presenting with infection were tested for SARs-COV-2 using RT-PCR. Children with Hb (50-65 g/L) and who were not transfused, were followed up using telemedicine with Hb re-checked in 24 h. RESULTS: A 45% drop in ER visits due to G6PD deficiency-related AHC during SARs-COV-2 pandemic in comparison to the previous 2 years was observed. 10% of patients presented with fever and all tested negative for COVID-19 by RT-PCR. 33% of patients had Hb < 50 g/L and were all transfused. 50% had Hb between 50 and 65 g/L, half of them (n = 49) did not receive transfusion and only two patients (4%) required transfusion upon follow up. A restrictive transfusion strategy was adopted and one of the reasons was a 39% drop in blood donation in participating centres. CONCLUSION: Fewer G6PD-deficient children with AHC visited the ER during SARs-COV-2 and most tolerated lower Hb levels. Telemedicine was an efficient tool to support their families. A restrictive transfusion strategy was clear in this study.

Hemolytic Anemia Complicating COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has been associated with a spectrum of reported hematological complications ranging from immune cytopenias to thromboembolic manifestations of coagulopathy. Moreover, there have been documented cases of hemolytic anemia associated with COVID-19 infection which have been mainly attributed to development of autoantibodies. We report a case of an African-American patient who presented with hemolytic anemia in the second week after his COVID-19 diagnosis. Throughout this report, we explore the potential immune and non-immune etiologies that contributed to the patient's hemolytic anemia in the setting of COVID-19 infection guided by a review of literature.

Glucose-6-Phosphate Dehydrogenase Deficiency-Associated Hemolytic Anemia and Methemoglobinemia in a Patient Treated With Hydroxychloroquine in the Era of COVID-19.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells worldwide. The severity of hemolytic anemia varies among individuals with G6PD deficiency, depending on the genetic variant in the G6PD gene; this makes the diagnosis of the condition more challenging in some cases. In this report, we present a case of severe hemolytic anemia and methemoglobinemia in a patient with G6PD deficiency who had been exposed to hydroxychloroquine prescribed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To the best of our knowledge and based on a literature search, this is one of the first case reports in the literature about hemolytic crisis and methemoglobinemia in a patient with critical illness due to severe coronavirus disease 2019 (COVID-19) who was exposed to hydroxychloroquine. It is critical for physicians and caregivers to recognize the effects of oxidative stressors such as hydroxychloroquine, particularly in this era of the COVID-19 pandemic and in regions with a high prevalence of G6PD deficiency, for the appropriate management of this unique subset of patients.

This is not a pipe - But how harmful is electronic cigarette smoke.

This issue of the Biomedical Journal tells us about the risks of electronic cigarette smoking, variations of SARS-CoV-2 and ACE2, and how COVID-19 affects the gastrointestinal system. Moreover, we learn that cancer immunotherapy seems to work well in elderly patients, how thyroid hormones regulate noncoding RNAs in a liver tumour context, and that G6PD is a double-edged sword of redox signalling. We also discover that Perilla leaf extract could inhibit SARS-CoV-2, that artificial neural networks can diagnose COVID-19 patients and predict vaccine epitopes on the Epstein-Barr Virus, and that men and women have differential inflammatory responses to physical effort. Finally, the surgical strategies for drug-resistant epilepsy, computer-supervised double-jaw surgery, dental pulp stem cell motility, and the restitution of the brain blood supply after atherosclerotic stroke are discussed.

Glucose-6-phosphate dehydrogenase inhibitor for treatment of severe COVID-19: Polydatin.

The COVID-19 pandemic as the largest global public health crisis is now considered as an emergency at the World Health Organization (WHO). As there is no specific therapy for SARS-CoV-2 infection at present and also because of the long time it takes to discover a new drug and the urgent need to respond urgently to a pandemic infection. Perhaps the best way right now is to find an FDA-approved drug to treat this infection. Oxidative stress and inflammation play a vital role in the progression of tissue injury in COVID-19 patients; furthermore, the G6PD activation is related to increased oxidative inflammation in acute pulmonary injury. In this regard, we propose a new insight that may be a good strategy for this urgency. Exploiting G6PD through inhibiting G6PD activity by modifying redox balance, metabolic switching and protein-protein interactions can be proposed as a new approach to improving patients in severe stage of COVID 19 through various mechanisms. Polydatin is isolated from many plants such as Polygonum, peanuts, grapes, red wines and many daily diets that can be used in severe stage of COVID-19 as a G6PD inhibitor. Furthermore, polydatin possesses various biological activities such as anti-inflammatory, antioxidant, immunoregulatory, nephroprotective, hepatoprotective, anti-arrhythmic and anti-tumor. Our hypothesis is that the consumption of antioxidants such as Polydatin (a glucoside of resveratrol) as a complementary therapeutic approach may be effective in reducing oxidative stress and inflammation in patients with COVID-19.

Therapeutic Intervention of COVID-19 by Natural Products: A Population-Specific Survey Directed Approach.

To date very few promising leads from natural products (NP) secondary metabolites with antiviral and immunomodulatory properties have been identified for promising/potential intervention for COVID-19. Using in-silico docking studies and genome based various molecular targets, and their in vitro anti-SARS CoV-2 activities against whole cell and/or selected protein targets, we select a few compounds of interest, which can be used as potential leads to counteract effects of uncontrolled innate immune responses, in particular those related to the cytokine storm. A critical factor for prevention and treatment of SARS-CoV-2 infection relates to factors independent of viral infection or host response. They include population-related variables such as concurrent comorbidities and genetic factors critically relevant to COVID-19 health disparities. We discuss population risk factors related to SARS-CoV-2. In addition, we focus on virulence related to glucose-6-phosphate dehydrogenase deficiency (G6PDd), the most common human enzymopathy. Review of data on the response of individuals and communities with high prevalence of G6PDd to NP, prompts us to propose the rationale for a population-specific management approach to rationalize design of therapeutic interventions of SARS-CoV-2 infection, based on use of NP. This strategy may lead to personalized approaches and improve disease-related outcomes.

Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review.

The coronavirus disease 2019 (COVID-19) is until today a global health emergency. In an immense effort, effective 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 effect of CQ/HCQ to treat and/or prevent COVID-19 infection has caused global attention. However, concern regarding possible hemolysis in G6PD-deficient COVID-19 patients exists and for this reason, the association between HCQ and G6PD deficiency (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-Deficient Patients with COVID-19?", reporting all cases of HCQ in G6PD deficient 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 difficult to reach a final verdict about the definitive 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-inflammatory cytokine and inflammasome 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 effective, safe, and well tolerated in G6PD deficient patients, must be redefined in these patients with COVID-19.As consequence, answering the question: "Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Deficient Patients with COVID-19?", we state that it is risky to believe that HCQ may be an "innocent bystander" in G6PD-deficient COVID-19 patients.